Tranexamic acid reduces red cell transfusion better than epsilon-aminocaproic acid or placebo in liver transplantation. Reduction of blood transfusion requirement in open heart surgery by administration of high doses of aprotinin--preliminary results. Tranexamic acid reduces bleeding after cardiopulmonary bypass when compared to epsilon aminocaproic acid and placebo. The prophylactic use of tranexamic acid and aprotinin in orthotopic liver transplantation: a comparative study. Use of tranexamic acid for an effective blood conservation strategy after total knee arthroplasty. Aprotinin reduces red blood cell transfusion in orthotopic liver transplantation: a prospective, randomized, double-blind study. Ultra-low dose aprotinin effects on reducing the need for blood transfusion in cardiac surgery. Does aprotinin really reduce blood loss in orthotopic liver transplantation? Aprotinin for coronary bypass operations: efficacy, safety, and influence on early saphenous vein graft patency. A multicenter, randomized, double-blind, placebo-controlled study. Aprotinin enhances the endogenous release of interleukin-10 after cardiac operations. Mini-dose pump-prime aprotinin inhibited enhanced fibrinolytic activity and reduced blood loss and transfusion requirements after coronary artery bypass surgery. Comparison of blood-conservation strategies in cardiac surgery patients at high risk for bleeding. Amelioration of the bleeding tendency of preoperative aspirin after aortocoronary bypass grafting. Tranexamic acid reduces blood loss and transfusion in reoperative cardiac surgery. Tranexamic acid to reduce blood loss after bilateral total knee arthroplasty: a prospective, randomized double blind study. A possible association between aprotinin and improved survival after radical surgery for mesothelioma. Continuous small-dose aprotinin controls fibrinolysis during orthotopic liver transplantation. Influence of high-dose aprotinin treatment on blood loss and coagulation patterns in patients undergoing myocardial revascularization. Aprotinin decreases exposure to allogeneic blood during primary unilateral total hip replacement. High-dose aprotinin in cardiac surgery: three years' experience in 1,784 patients. Influence of high-dose aprotinin on anticoagulation, heparin requirement, and celite- and kaolin-activated clotting time in heparin-pretreated patients undergoing open-heart surgery. A double-blind, placebo-controlled study. Platelet function during cardiac surgery and cardiopulmonary bypass with low-dose aprotinin. Epsilon-aminocaproic acid in coronary artery bypass graft surgery: preincision or postheparin? Aprotinin in elective primary bypass surgery. Graft patency and clinical efficacy. A randomized trial of tranexamic acid in combination with cell salvage plus a meta-analysis of randomized trials evaluating tranexamic acid in off-pump coronary artery bypass grafting. Tranexamic acid reduces transfusions and mediastinal drainage in repeat cardiac surgery. Tranexamic acid reduces bleeding and the need for blood transfusion in primary myocardial revascularization. Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation. [Reducing bleeding during extracorporeal circulation interventions by high doses of aprotinin]. Tranexamic acid decreases external blood loss but not hidden blood loss in total knee replacement. Tranexamic acid in aortic valve replacement. Aprotinin in primary valve replacement and reconstruction: a multicenter, double-blind, placebo-controlled trial. Low-dose postoperative aprotinin reduces mediastinal drainage and blood product use in patients undergoing primary coronary artery bypass grafting who are taking aspirin: a prospective, randomized, double-blind, placebo-controlled trial. Prophylactic tranexamic acid decreases bleeding after cardiac operations. The use of tranexamic acid to reduce postoperative bleeding following cardiac surgery: a double-blind randomized trial. Additional postbypass administration of tranexamic acid reduces blood loss after cardiac operations. Randomized, placebo-controlled, double-blind study of an ultra-low-dose aprotinin regimen in reoperative and/or complex cardiac operations. Reduction in blood loss and blood use after cardiopulmonary bypass with high dose aprotinin (Trasylol). Tranexamic acid is effective in decreasing postoperative bleeding and transfusions in primary coronary artery bypass operations: a double-blind, randomized, placebo-controlled trial. Tranexamic acid reduces early post-operative blood loss after total knee arthroplasty: a prospective randomised controlled trial of 29 patients. Heparin-level-based anticoagulation management during cardiopulmonary bypass: a pilot investigation on the effects of a half-dose aprotinin protocol on postoperative blood loss and hemostatic activation and inflammatory response. Defining the role of aprotinin in heart transplantation. Reduced blood loss by aprotinin in thoracic surgical operations associated with high risk of bleeding. A placebo-controlled, randomized phase IV study. Aprotinin counterbalances an increased risk of peri-operative hemorrhage in CABG patients pre-treated with Aspirin. Decreased postoperative drainage with addition of epsilon-aminocaproic acid before cardiopulmonary bypass. Reducing allogeneic transfusion in cardiac surgery: a randomized double-blind placebo-controlled trial of antifibrinolytic therapies used in addition to intra-operative cell salvage. Comparison of the effects of aprotinin and tranexamic acid on blood loss and related variables after cardiopulmonary bypass. Aprotinin does not diminish blood loss in elective operations for infrarenal abdominal aneurysms: a randomized double-blind controlled trial. Reduction of blood loss with tranexamic acid in primary total hip replacement surgery. Does aprotinin reduce blood loss in total hip arthroplasty? Low-dose aprotinin infusion is not clinically useful to reduce bleeding and transfusion of homologous blood products in high-risk cardiac surgical patients. Tranexamic acid reduces blood loss and blood transfusions in primary total hip arthroplasty: a prospective randomized double-blind study in 40 patients. Changes in coagulation patterns, blood loss and blood use after cardiopulmonary bypass: aprotinin vs tranexamic acid vs epsilon aminocaproic acid. Blood conservation techniques and platelet function in cardiac surgery. Kidney-specific proteins in patients receiving aprotinin at high- and low-dose regimens during coronary artery bypass graft with cardiopulmonary bypass. Prospective randomized placebo-controlled trial of aprotinin for elective aortic reconstruction. The use of low-dose aprotinin, epsilon-aminocaproic acid or tranexamic acid for prevention of mediastinal bleeding in patients receiving aspirin before coronary artery bypass operations. Differential effects of epsilon-aminocaproic acid and aprotinin on matrix metalloproteinase release in patients following cardiopulmonary bypass. Lower cardiac troponin T levels in patients undergoing cardiopulmonary bypass and receiving high-dose aprotinin therapy indicate reduction of perioperative myocardial damage. Aprotinin but not epsilon-aminocaproic acid decreases interleukin-10 after cardiac surgery with extracorporeal circulation: randomized, double-blind, placebo-controlled study in patients receiving aprotinin and epsilon-aminocaproic acid. Effect of aprotinin (Trasylol) on aorta-coronary bypass graft patency. Bone bleeding during total hip arthroplasty after administration of tranexamic acid. "Low-dose" aprotinin modifies hemostasis but not proinflammatory cytokine release. The effect of epsilon-aminocaproic acid and aprotinin on fibrinolysis and blood loss in patients undergoing primary, isolated coronary artery bypass surgery: a randomized, double-blind, placebo-controlled, noninferiority trial. The effect of epsilon aminocaproic acid on blood loss in patients who undergo primary total hip replacement: a pilot study. Randomized study of aprotinin effect on transfusions and blood loss in primary THA. Tranexamic acid reduces blood loss in total hip replacement surgery. Comparison of epsilon aminocaproic acid and low-dose aprotinin in cardiopulmonary bypass: efficiency, safety and cost. Intraoperative antifibrinolysis and blood-saving techniques in cardiac surgery. Prospective trial of 3 antifibrinolytic drugs. Comparative study of antifibrinolytic drugs in orthotopic liver transplantation. Aprotinin reduces cardiac troponin I release and inhibits apoptosis of polymorphonuclear cells during off-pump coronary artery bypass surgery. Tranexamic acid and aprotinin in low- and intermediate-risk cardiac surgery: a non-sponsored, double-blind, randomised, placebo-controlled trial. Ultra-low dose aprotinin decreases transfusion requirements and is cost effective in coronary operations. Postoperative bleeding after coronary revascularization. Comparison between tranexamic acid and epsilon-aminocaproic acid. [Use of high doses of aprotinin in cardiac surgery]. A double-blind, placebo-controlled trial of epsilon-aminocaproic acid for reducing blood loss in coronary artery bypass grafting surgery. Analyses of coronary graft patency after aprotinin use: results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial. Does aprotinin influence endothelial-associated coagulation in cardiac surgery? [Aprotinin in cardiosurgery: a randomized prospective study with different protocols for use]. High-dose epsilon-aminocaproic acid versus aprotinin: antifibrinolytic efficacy in first-time coronary operations. Aprotinin versus desmopressin for patients undergoing operations with cardiopulmonary bypass. A double-blind placebo-controlled study. The postoperative blood-sparing efficacy of oral versus intravenous tranexamic acid after total knee replacement. High-dose aprotinin: hemostatic effects in open heart operations. [The effects of aprotinin. Blood loss and coagulation parameters in orthotopic liver transplantation: A clinical-experimental, prospective and randomized double-blind study]. Tranexamic acid reduces blood loss in off-pump coronary artery bypass surgery. The influence of aprotinin and tranexamic acid on platelet function and postoperative blood loss in cardiac surgery. [Aprotinin 2 million KIU reduces perioperative blood loss in patients undergoing primary total hip replacement]. Aprotinin does not impair renal haemodynamics and function after cardiac surgery. Is use of aprotinin safe with deep hypothermic circulatory arrest in aortic surgery? Investigations on blood coagulation. Fibrinolytic activity and bleeding after cardiac surgery with cardiopulmonary bypass and low-dose aprotinin therapy. A randomized trial of aprotinin (Trasylol) on blood loss, blood product requirement, and myocardial injury in total arterial grafting. Timing of the administration of tranexamic acid for maximum reduction in blood loss in arthroplasty of the knee. The effect of two different doses of aprotinin on hemostasis in cardiopulmonary bypass surgery: similar transfusion requirements and blood loss. Preoperative platelet dysfunction increases the benefit of aprotinin in cardiopulmonary bypass. Modifying risk for extracorporeal circulation: trial of four antiinflammatory strategies. Tranexamic acid reduces the need for allogenic red blood cell transfusions in patients undergoing total hip replacement. High-dose aprotinin modulates the balance between proinflammatory and anti-inflammatory responses during coronary artery bypass graft surgery. Aprotinin decreases the incidence of cognitive deficit following CABG and cardiopulmonary bypass: a pilot randomized controlled study. A pump-prime aprotinin dose in cardiac surgery: appraisal of its effects on the hemostatic system. Aprotinin reduces blood loss in off-pump coronary artery bypass (OPCAB) surgery. Reduction of blood loss and transfusion requirements after coronary artery bypass grafting: similar efficacy of tranexamic acid and aprotinin in aspirin-treated patients. Aprotinin and transfusion requirements in orthotopic liver transplantation: a multicentre randomised double-blind study. EMSALT Study Group. Tranexamic acid reduces blood loss in cemented hip arthroplasty: a randomized, double-blind study of 39 patients with osteoarthritis. Prophylactic tranexamic acid in elective, primary coronary artery bypass surgery using cardiopulmonary bypass. Tranexamic acid radically decreases blood loss and transfusions associated with total knee arthroplasty. Effect of aprotinin on the red cell immunity in cardiopulmonary bypass. Use of aprotinin in knee replacement surgery. Effects of aprotinin on blood loss, heparin monitoring tests, and heparin doses in patients undergoing coronary artery bypass surgery. The prophylactic effect of aprotinin on intraoperative bleeding in liver transplantation: a randomized clinical study. The effect of tourniquet application, tranexamic acid, and desmopressin on the procoagulant and fibrinolytic systems during total knee replacement. The effect of coagulation protection with combination of epsilon aminocaproic acid and plasma saver in open-heart surgery. A randomized clinical trial investigating the relationship between aprotinin and hypercoagulability in off-pump coronary surgery. Hemostatic efficacy of dipyridamole, tranexamic acid, and aprotinin in coronary bypass grafting. Aprotinin reduces intraoperative and postoperative blood loss in membrane oxygenator cardiopulmonary bypass. Effect of reduced aprotinin dosage on blood loss and use of blood products in patients undergoing cardiopulmonary bypass. Reduction of blood loss using high-dose aprotinin in major orthopaedic surgery: a prospective, double-blind, randomised and placebo-controlled study. Cost-benefit and efficacy of aprotinin compared with epsilon-aminocaproic acid in patients having repeated cardiac operations: a randomized, blinded clinical trial. Aprotinin significantly decreases bleeding and transfusion requirements in patients receiving aspirin and undergoing cardiac operations. Aprotinin for patients exposed to clopidogrel before off-pump coronary bypass. Heparin-bonded cardiopulmonary bypass circuits reduce the rate of red blood cell transfusion during elective coronary artery bypass surgery. Is reduced systemic heparinization justified with heparin-bonded bypass circuits in cardiac surgery?--Experience with and without aprotinin. Tranexamic Acid reduces perioperative blood loss in adult patients having spinal fusion surgery. Tranexamic acid in total hip arthroplasty saves blood and money: a randomized, double-blind study in 100 patients. Effects of minimal-dose aprotinin on coronary artery bypass grafting. Tranexamic acid given intraoperatively reduces blood loss after total knee replacement: a randomized, controlled study. Impact of tranexamic acid vs. aprotinin on blood loss and transfusion requirements after cardiopulmonary bypass: a prospective, randomised, double-blind trial. Aprotinin and tranexamic acid for high transfusion risk cardiac surgery. Is there a phase of hypercoagulability when aprotinin is used in cardiac surgery? Tranexamic acid, given at the end of the operation, does not reduce postoperative blood loss in hip arthroplasty. Effects of minimal dose aprotinin on blood loss and fibrinolytic system-complement activation in coronary artery bypass grafting surgery. Tranexamic acid and primary coronary artery bypass surgery: a prospective study. Cytokine release and neutrophil activation are not prevented by heparin-coated circuits and aprotinin administration. Tranexamic acid and aprotinin in primary cardiac operations: an analysis of 220 cardiac surgical patients treated with tranexamic acid or aprotinin. [Comparison of the effects of epsilon-aminocaproic acid and aprotinin on intra- and postoperative bleeding in heart surgery]. Low doses of aprotinin in aortocoronary bypass surgery--advantages and disadvantages. Tranexamic acid reduces postoperative bleeding in off-pump coronary artery bypass grafting. Influence of aprotinin on early graft thrombosis in patients undergoing myocardial revascularization. Platelet protection by low-dose aprotinin in cardiopulmonary bypass: electron microscopic study. [Reduction of per- and postoperative blood loss with aprotinin (Trasylol) during extracorporeal circulation]. Effects of aprotinin on hemostatic mechanisms during cardiopulmonary bypass. Randomized placebo-controlled double-blind study of three aprotinin regimens in primary cardiac surgery. Effects of tranexamic acid on postoperative bleeding and related hematochemical variables in coronary surgery: Comparison between on-pump and off-pump techniques. Hemostatic effects of aprotinin, tranexamic acid and epsilon-aminocaproic acid in primary cardiac surgery. Tranexamic acid in off-pump coronary surgery: a preliminary, randomized, double-blind, placebo-controlled study. Tranexamic acid compared with high-dose aprotinin in primary elective heart operations: effects on perioperative bleeding and allogeneic transfusions. Aprotinin reduces blood loss and the need for transfusion in orthognathic surgery. Antifibrinolytic therapy and perioperative blood loss in cancer patients undergoing major orthopedic surgery. Prophylactic treatment of postperfusion bleeding using EACA. Aprotinin prevents cardiopulmonary bypass-induced platelet dysfunction. A scanning electron microscope study. The impact of aprotinin on coronary artery bypass graft patency. Reduction of bleeding after heart operations through the prophylactic use of epsilon-aminocaproic acid. Antifibrinolytic therapy during cardiopulmonary bypass reduces proinflammatory cytokine levels: a randomized, double-blind, placebo-controlled study of epsilon-aminocaproic acid and aprotinin. Effect of epsilon aminocaproic acid on red-cell transfusion requirements in major spinal surgery. Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial. Economic evaluation of high-dose and low-dose aprotinin therapy during cardiopulmonary bypass. The effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic response after cardiac surgery. The effect of prophylactic epsilon-aminocaproic acid on bleeding, transfusions, platelet function, and fibrinolysis during coronary artery bypass grafting. The efficacy and safety of aprotinin for hemostasis during intracranial surgery. Tranexamic acid and early saphenous vein graft patency in conventional coronary artery bypass graft surgery: a prospective randomized controlled clinical trial. Effects of epsilon-aminocaproic acid and aprotinin on leukocyte-platelet adhesion in patients undergoing cardiac surgery. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. Fibrinolytic inhibition with tranexamic acid reduces blood loss and blood transfusion after knee arthroplasty: a prospective, randomised, double-blind study of 86 patients. High-dose aprotinin in cardiac surgery--a prospective, randomized study. Blood conservation with tranexamic acid in total hip arthroplasty: a randomized, double-blind study in 40 primary operations. Fibrinolysis-adjusted perioperative low-dose aprotinin reduces blood loss in bypass operations. Tranexamic acid reduces bleeding after off-pump coronary artery bypass grafting. Decreasing use of donated blood and reduction of bleeding after orthotopic heart transplantation by use of aprotinin. Postoperative use of aprotinin in cardiac operations: an alternative to its prophylactic use. Aprotinin in coronary operation with cardiopulmonary bypass: does "low-dose" aprotinin inhibit the inflammatory response? Aprotinin versus placebo in major orthopedic surgery: a randomized, double-blinded, dose-ranging study. Postoperative aprotinin: effect on blood loss and transfusion requirements in cardiac operations. Combination of acute preoperative plateletpheresis, cell salvage, and aprotinin minimizes blood loss and requirement during cardiac surgery. Tranexamic acid reduces blood transfusion in total knee arthroplasty even when a blood conservation program is applied. Tranexamic acid does not correct the haemostatic impairment caused by hydroxyethyl starch (200 kDa/0.5) after cardiac surgery. Intravenous tranexamic acid use in myomectomy: a prospective randomized double-blind placebo controlled study. Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial. Tranexamic acid and aprotinin reduce postoperative bleeding and transfusions during primary coronary revascularization. Does aprotinin influence the inflammatory response to cardiopulmonary bypass in patients? The efficacy of antifibrinolytics in the reduction of blood loss during complex adult reconstructive spine surgery. Influence of ultra-low dose Aprotinin on thoracic surgical operations: a prospective randomized trial. [Aprotinin (Antilysin Spofa)--its effect on decreasing hemorrhage in the postoperative period in hip arthroplasty]. Systematic use of aprotinin in cardiac surgery: influence on total homologous exposure and hospital cost. Effect of aprotinin on need for blood transfusion after repeat open-heart surgery. Aprotinin and dipyridamole for the safe reduction of postoperative blood loss. Aprotinin reduces blood loss in patients undergoing elective liver resection. [Clinical comparative studies on effect of tranexamic acid on blood loss associated with total knee arthroplasty]. Prophylactic tranexamic acid and epsilon-aminocaproic acid for primary myocardial revascularization. Effect of tranexamic acid on blood loss reduction after cardiopulmonary bypass. Aprotinin for primary coronary artery bypass grafting: a multicenter trial of three dose regimens. Reduction of blood loss and transfusion requirement by aprotinin in posterior lumbar spine fusion. Tranexamic acid reduces blood loss after cementless total hip arthroplasty-prospective randomized study in 40 cases. A comparison of the effects of tranexamic acid and low-dose aprotinin on blood loss and homologous blood usage in patients undergoing cardiac surgery. A multicenter, double-blind, placebo-controlled trial of aprotinin for reducing blood loss and the requirement for donor-blood transfusion in patients undergoing repeat coronary artery bypass grafting. Recombinant aprotinin in coronary artery bypass graft operations. Reducing perioperative blood loss in patients undergoing total hip arthroplasty. Comparison of the effects of aprotinin and tranexamic acid on blood loss and red blood cell transfusion requirements during the late stages of liver transplantation. Randomized study of aprotinin and DDAVP to reduce postoperative bleeding after cardiopulmonary bypass surgery. Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic acid. Double-blind, randomized clinical trial. Single-dose tranexamic acid reduces postoperative bleeding after coronary surgery in patients treated with aspirin until surgery. Perioperative parenteral tranexamic acid in liver tumor resection: a prospective randomized trial toward a "blood transfusion"-free hepatectomy. Effect of prophylactic epsilon-aminocaproic acid on blood loss and transfusion requirements in patients undergoing first-time coronary artery bypass grafting. A randomized, prospective, double-blind study. High-dose aprotinin reduces blood loss in patients undergoing total hip replacement surgery. Hemostatic effects of tranexamic acid and desmopressin during cardiac surgery. Fibrinolytic inhibitors in off-pump coronary surgery: a prospective, randomized, double-blind TAP study (tranexamic acid, aprotinin, placebo). Aprotinin shows both hemostatic and antithrombotic effects during off-pump coronary artery bypass grafting. Comparison of two doses of aprotinin in patients receiving aspirin before coronary bypass surgery. Operations on the thoracic aorta and hypothermic circulatory arrest: is aprotinin safe? Aprotinin and epsilon aminocaproic acid are effective in reducing blood loss after primary total hip arthroplasty--a prospective randomized double-blind placebo-controlled study. [Comparison of effects of aprotinin and tranexamic acid on blood loss in heart surgery]. Aprotinin decreases blood loss and homologous transfusions in patients undergoing major orthopedic surgery. Leukocyte integrin expression in patients undergoing cardiopulmonary bypass. The efficacy of single-dose aprotinin 2 million KIU in reducing blood loss and its impact on the incidence of deep venous thrombosis in patients undergoing total hip replacement surgery. The effects of aprotinin and steroids on generation of cytokines during coronary artery surgery. Efficacy and safety of aprotinin in aortocoronary bypass and valve replacement operations: a placebo-controlled randomized double-blind study. Aprotinin therapy for reoperative myocardial revascularization: a placebo-controlled study. Tranexamic acid (Cyklokapron) reduces perioperative blood loss associated with total knee arthroplasty. [Comparison between low and high doses of aprotinin in heart surgery]. Single dose aprotinin in routine cardiac surgery. Tranexamic acid reduces postbypass blood use: a double-blinded, prospective, randomized study of 210 patients. The effect of tranexamic acid on reducing blood loss in cementless total hip arthroplasty under epidural anesthesia. The dose-response relationship of tranexamic acid. Does tranexamic acid reduce blood loss in off-pump coronary artery bypass? Aprotinin preserves hemostasis in aspirin-treated patients undergoing cardiopulmonary bypass. Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin versus autologous fresh whole blood transfusion. Hemostatic effects of tranexamic acid in elective thoracic aortic surgery: a prospective, randomized, double-blind, placebo-controlled study.
We evaluated the efficacy of the prophylactic administration of epsilon-aminocaproic acid and tranexamic acid for reducing blood product requirements in orthotopic liver transplantation (OLT) in a prospective, double-blinded study performed in 132 consecutive patients. Patients were randomized to three groups and given one of three drugs prophylactically: tranexamic acid, 10 mg. kg(-1). h(-1); epsilon-aminocaproic acid, 16 mg. kg(-1). h(-1), and placebo (isotonic saline). Perioperative management was standardized. Coagulation tests, thromboelastogram, and blood requirements were recorded during OLT and in the first 24 h. There were no differences in diagnosis, Child score, or preoperative coagulation tests among groups. Administration of packed red blood cells was significantly reduced (P = 0.023) during OLT in the tranexamic acid group, but not in the epsilon-aminocaproic acid group. There were no differences in transfusion requirements after OLT. Thromboembolic events, reoperations, and mortality were similar in the three groups. Prophylactic administration of tranexamic acid, but not epsilon-aminocaproic acid, significantly reduces total packed red blood cell usage during OLT.
                In a randomized study of 132 consecutive patients undergoing liver transplantation, we found that tranexamic acid, but not epsilon-aminocaproic acid, reduced intraoperative total packed red blood cell transfusion. Reduction of homologous blood requirement in cardiac surgery is of increasing interest and may be achieved by various technical and pharmacological means. High-dose aprotinin (about 840 mg, equivalent to 6 million Kallikrein inactivator units), a serine proteinase inhibitor, was administered during open heart surgery to 60 patients refusing homologous blood transfusions or suspected to have an increased risk of bleeding. As a significant decrease in donor blood requirement could be observed, a prospective, randomised double blind study in 80 male patients undergoing primary coronary surgery with high-dose aprotinin administration was performed. Mean blood loss was reduced by 45.9% (652 ml in the treated vs 1204 ml in the untreated group, p less than 0.01) and the mean amount transfused was decreased by 74.2% (242 ml vs 937 ml, p less than 0.01). No homologous blood was needed in 57.9% of the aprotinin-treated patients and in 31.6% of patients not treated with aprotinin. Perioperative bleeding following coronary artery bypass grafting (CABG) is associated with increased blood product usage. Although aprotonin is effective in reducing perioperative blood loss, excessive cost prohibits routine utilization. Epsilon aminocaproic acid (EACA) and tranexamic acid (TA) are inexpensive antifibrinolytic agents, which, when given prophylactically, may reduce blood loss. The present study was undertaken to compare the efficacy of TA and EACA in reducing perioperative blood loss.
                The study population consisted of first-time CABG patients. Patients were allocated in a prospective double-blind fashion: (1) group EACA (loading dose 15 mg/kg, continuous infusion 10 mg/kg per hour for 6 hours, N = 20); (2) group TA (loading dose 15 mg/kg, continuous infusion 1 mg/kg per hour for 6 hours, N = 20); (3) control group (infusion of normal saline for 6 hours, N = 19).
                Treatment groups were similar preoperatively. No significant difference in intraoperative blood loss or perioperative use of blood products was noted. D-dimer concentration was elevated in the control group compared to the EACA and TA groups (p < 0.05). Group TA had less postoperative blood loss than the EACA and control groups at 6 and 12 hours postoperatively (p < 0.05). TA had reduced total blood loss (600 +/- 49 mL) postoperatively compared to EACA (961 +/- 148 mL) and control (1060 +/- 127 mL, p < 0.05).
                TA and EACA effectively inhibited fibrinolytic activity intraoperatively and throughout the first 24 hours postoperatively. TA was more effective in reducing blood loss postoperatively following CABG. This suggests that TA may be beneficial as an effective and inexpensive antifibrinolytic in first-time CABG patients. The efficacy of tranexamic acid (TA) and aprotinin (AP) in reducing blood product requirements in orthotopic liver transplantation (OLT) was compared in a prospective, randomized and double-blind study. One hundred and twenty seven consecutive patients undergoing OLT were enrolled; TA was administered to 64 OLT patients at a dose of 10mg /kg/h and aprotinin was administered to 63 OLT patients at a loading dose of 2 x 10(6) KIU followed by an infusion of 500,000 KIU/h. The portocaval shunt could not be performed in 14 OLT patients in the TA group and in 13 OLT patients in the AP group. However, all OLT patients that received either drug were included in the analysis. Perioperative management was standardized. Hemogram, coagulation tests, and blood product requirements were recorded during OLT and during the first 24 hours. No differences in diagnosis, Child score, preoperative coagulation tests, and intraoperative data were found between groups. No significant differences were observed in hemogram and intraoperative coagulation tests with the exception of activated partial thromboplastin time (aPTT). Similarly, there were no intergroup differences in transfusion requirements. Thromboembolic events, reoperations and mortality were similar in both groups. In conclusion, administration of regular doses of TA and AP during OLT did not result in large differences between the two groups. We have investigated the effect of treatment with tranexamic acid, an inhibitor of fibrinolysis, on blood loss, blood transfusion requirements and blood coagulation in a randomized, double-blind, placebo-controlled study of 42 patients after total knee arthroplasty. Tranexamic acid 15 mg kg-1 (n = 21) or an equivalent volume of normal saline (n = 21) was given 30 min before surgery and subsequently every 8 h for 3 days. Coagulation and fibrinolysis values, blood loss and blood units administered were measured before administration of tranexamic acid, 8 h after the end of surgery and at 24 and 72 h after operation. Coagulation profile was examined (bleeding time, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), plasminogen, beta-thromboglobulin and fibrinogen). Fibrinolysis was evaluated by measurement of concentrations of D-dimer and fibrinogen degradation products (FDP). Total blood loss in the tranexamic acid group was 678 (SD 352) ml compared with 1419 (607) ml in the control group (P < 0.001), and occurred primarily during the first 24 h after surgery. Thirteen patients received 1-5 u. of packed red blood cells in the control group compared with two patients in the tranexamic acid group, who received 3 u. (P < 0.001). Postoperative packed cell volume values were higher in the tranexamic acid group despite fewer blood transfusions. Postoperative concentrations of plasminogen were decreased significantly in the tranexamic acid group (P < 0.001). Platelet count, PT, aPTT, bleeding time, beta-thromboglobulin, fibrinogen and FDP concentrations did not differ between groups, but D-dimer concentrations were increased in the control group. Thromboembolic complications occurred in two patients in the control group compared with none in the tranexamic acid group. The effect of an aprotinin infusion on blood and blood product transfusion during adult primary orthotopic liver transplantation (OLT) was investigated in a prospective, randomized, double-blind study. Sixty-three patients were enrolled; 33 patients were administered an aprotinin regimen of a 1,000,000-KIU loading dose, followed by a 250,000-KIU/h infusion during surgery, and 30 patients were administered equivalent volumes of normal saline. Red blood cell (RBC) and blood product transfusion intraoperatively and for the first 24 hours postoperatively was by protocol. Intraoperative coagulation testing and thromboelastography (TEG; Hemoscope Corp, Skokie, IL) were performed. Intraoperative RBC transfusion was significantly less in the aprotinin group versus controls: median, 5 units (interquartile range [IQR], 3 to 9 units) versus 7 units (IQR, 5 to 16 units; P =.0016). No significant differences were found for intraoperative blood product transfusion or transfusion of RBCs or blood products in the 24-hour postoperative period. No significant differences were observed in intraoperative coagulation testing or TEG parameters. We conclude that aprotinin infusion reduces RBC transfusion requirements in OLT. To assess the effects of ultra-low dose one million kallikrein inhibitor units (KIU) of aprotinin on bleeding and the need for transfusion after cardiac surgery.
                We carried out this randomized clinical trial on 162 cardiac surgery patients in Shahid Madani Hospital, Tabriz, Iran from April 2004 to December 2005. The patients were randomly divided into 2 groups of 81 individuals. In the aprotinin group, 0.5 million KIU infused before and 0.5 million KIU during cardiopulmonary bypass. In the placebo group, 100 ml normal saline was infused as above. The need to use fresh frozen plasma (FFP), packed red blood cells (PRBCs) transfusion during, after operation, the rate of chest tubes drainage at 6, 12 and 24 hours after surgery were measured in 2 groups.
                Chest tubes drainage at 6 hours after surgery was 190 +/- 24 ml in the aprotinin group and 266 +/- 33 ml in the placebo group (p=0.066). The amount of bleeding at 12 and 24 hours was significantly different between 2 groups (p=0.048, p=0.009). The frequency of blood products transfusion in the aprotinin group was 68% and in the placebo group was 75% (p=0.02). The number of PRBCs and FFP units transfused were significantly lower in the aprotinin group (p=0.000, p=0.005). Total amount of blood and products transfusion in the aprotinin group was 2.56 +/- 0.27 units and in placebo group it was 4.37 +/- 0.27 units (p=0.0001).
                Results indicate that the use of one million KIU of aprotinin in cardiac surgery is effective in reducing postoperative bleeding and transfusion requirements. nan The purpose of this study was to evaluate the efficacy and safety of aprotinin in a U.S. population of patients undergoing coronary artery bypass grafting. Early vein graft patency rates were assessed by ultrafast computed tomography. A total of 216 patients at five centers were randomized to receive either high-dose aprotinin or placebo during the operation; 151 patients underwent primary operation, and 65 underwent repeat procedures. Total blood product exposures in the primary group were 2.2 per patient receiving aprotinin as compared with 5.7 per patient receiving placebo (p = 0.010). The repeat group had 0.3 exposures per patient receiving aprotinin as compared with 10.7 per patient receiving placebo (p = < 0.001). Consistent reductions in the percent of patients requiring donor red blood cells and in the number of units of platelets, fresh frozen plasma, and cryoprecipitate required were associated with the use of aprotinin in both primary and repeat groups. Mortality was 5.6% in the aprotinin group and 3.7% in the placebo group (p = 0.517). In the primary group, clinical diagnoses of myocardial infarction were made in 8.9% of patients receiving aprotinin as compared with 5.6% of the patients receiving placebo (p = 0.435). In the repeat group, infarctions occurred in 10.3% of patients receiving aprotinin and 8.3% of patients receiving placebo (p = 1.000). Secondary analysis of electrocardiograms and available enzyme data showed no significant difference in infarction rates between the treatment groups. There was no difference in clinically significant renal dysfunction. The early vein graft patency rates were 92.0% in the aprotinin group and 95.1% in the placebo group (p = 0.248). In this study, aprotinin was effective in reducing bleeding and blood product transfusion rates, and its use was not associated with an increase in complications. An adverse effect on early vein graft patency rates was not demonstrated, but the number of grafts assessed was insufficient for absolute conclusions in this regard. Cardiopulmonary bypass (CPB) is characterized by the systemic release of proinflammatory cytokines, such as tumor necrosis factor-alpha and the interleukins 1 and 6, as well as endogenous antiinflammatory cytokines, including interleukin-10 (IL-10). Glucocorticoids reduce tumor necrosis factor-alpha plasma concentrations while enhancing IL-10 plasma concentrations after CPB. Aprotinin, a serine protease inhibitor used primarily to reduce blood loss after CPB, reduces CPB-induced proinflammatory cytokine tumor necrosis factor-alpha release similarly to glucocorticoids. This study evaluates the effect of full-dose aprotinin on the plasma concentrations of IL-10 after CPB.
                Twenty adults were randomized into a control (group C, n = 10) and a full-dose aprotinin-treated group (group A, n = 10). Plasma levels of IL-10 were measured by enzyme-linked immunosorbent assay technique at baseline (before anesthetic induction), and at 1 and 24 hours after CPB termination.
                A significant (p < 0.05) increase of IL-10 occurred in both groups at 1 and 24 hours after termination of CPB when compared with the same group at baseline. In group A, the increase in IL-10 was significantly greater than in group C (p < 0.05) at 24 hours after CPB.
                These results demonstrate an endogenous antiinflammatory response generated after CPB, characterized by IL-10 release, that is enhanced by aprotinin therapy. This study demonstrates a unique antiinflammatory activity of aprotinin that may be of clinical significance. Low-dose aprotinin in the pump during cardiopulmonary bypass (CPB) has been shown to improve postoperative hemostasis and platelet preservation. This investigation was undertaken to evaluate the effects of mini-dose pump prime only aprotinin (70 mg) on the hemostatic parameters and blood transfusion requirements in patients undergoing on-pump coronary artery bypass surgery (CABG).
                We studied 86 patients who underwent CABG. Forty patients received mini-dose aprotinin (500.000 KIU [70 mg] in the pump), and a control group of 46 did not. D-dimer level, full blood count, postoperative blood loss, and transfusion requirements were analyzed before, after one hour operation and first day after operation.
                Twenty-four-hour postoperative blood loss was significantly reduced in the aprotinin group (188+/- 51.5 ml vs. 818+/- 243.5 ml, [mean +/- standard deviation] p < 0.01). Patients in the aprotinin group also received significantly less banked blood posoperatively than the control group (1.20 +/- 0.52 vs. 3.33 +/- 1.13 Units/per patient (p < 0.04). One hour after operation, and 24 hours after operation D-dimer level was significantly reduced in the aprotinin group (p < 0.008 and p < 0.017, respectively).
                Mini dose pump-prime aprotinin reduces postoperative blood loss, transfusion requirements and yet confers hemostatic improvement through reduced fibrinolysis in patients undergoing routine coronary artery bypass grafting. Aprotinin and tranexamic acid are routinely used to reduce bleeding in cardiac surgery. There is a large difference in agent price and perhaps in efficacy.
                In a prospective, randomized, partially blinded study, 168 cardiac surgery patients at high risk for bleeding received either a full-dose aprotinin infusion, tranexamic acid (10-mg/kg load, 1-mg x kg(-1) x h(-1) infusion), tranexamic acid with pre-cardiopulmonary bypass autologous whole-blood collection (12.5% blood volume) and reinfusion after cardiopulmonary bypass (combined therapy), or saline infusion (placebo group).
                There were complete data in 160 patients. The aprotinin (n = 40) and combined therapy (n = 32) groups (data are median [range]) had similar reductions in blood loss in the first 4 h in the intensive care unit (225 [40-761] and 163 [25-760] ml, respectively; P = 0.014), erythrocyte transfusion requirements in the first 24 h in the intensive care unit (0 [0-3] and 0 [0-3] U, respectively; P = 0.004), and durations of time from end of cardiopulmonary bypass to discharge from the operating room (92 [57-215] and 94 [37, 186] min, respectively; P = 0.01) compared with the placebo group (n = 43). Ten patients in the combined therapy group (30.3%) required transfusion of the autologous blood during cardiopulmonary bypass for anemia.
                The combination therapy of tranexamic acid and intraoperative autologous blood collection provided similar reduction in blood loss and transfusion requirements as aprotinin. Cost analyses revealed that combined therapy and tranexamic acid therapy were the least costly therapies. Aspirin therapy is widely used in the treatment of cardiac disease. It has been recognized as a causative factor for increased bleeding and blood loss after open heart operations.
                To determine whether high-dose aprotinin maintained its efficacy in reducing blood loss in the presence of aspirin pretreatment in patients undergoing aortocoronary bypass, we performed a double blind study on 60 adult patients. Half received high-dose aprotinin (Trasylol) and half placebo.
                Total hemoglobin loss, the primary efficacy variable was reduced from 36.1 +/- 31.4 g (mean +/- SD) to 14.1 +/- 16.0 g (p = 0.002). Blood loss was reduced intraoperatively and total loss was reduced from 837.3 mL +/- 404.9 mL to 368.7 mL +/- 164.3 mL (p < 0.001). The number of patients who did not receive any donor blood products was significantly higher in the aprotinin-treated patients (56.7% versus 23.3%, p = 0.008). Activation of the clotting cascade was significantly less in the treated patients toward the end of cardiopulmonary bypass both by measurement of thrombin-antithrombin III complex (p < 0.0001) and prothrombin fragment 1 + 2 (p < 0.0001). D-Dimer generation was significantly less from the onset of bypass and after reversal of heparin in the aprotinin-treated patients (p < 0.0001).
                High-dose aprotinin was highly effective in reducing bleeding in this high-risk group of patients. Biochemical analyses suggest the mechanism by which aspirin increases blood loss after cardiopulmonary bypass is different from the blood-preserving effects of aprotinin, which is acting as an antifibrinolytic agent. The objective of this study was to assess the effect of tranexamic acid (TA), a synthetic antifibrinolytic, on blood loss and the need for transfusion of blood products following repeat cardiac valve surgery.
                After ethics committee approval, 41 patients scheduled for reoperative valve replacement were enrolled in this randomized, double blind, placebo controlled study. Patients were randomized to receive TA (10 g in 500 ml NSaline) or placebo (NSaline) as an iv bolus over 30 min, after anaesthesia induction and prior to skin incision. Intraoperative blood loss was assessed by estimating blood volume on drapes, weighing surgical sponges, and measuring suction bottle returns. Postoperative blood loss was measured from mediastinal chest tube drainage following surgery. Blood products were transfused according to a standardized protocol.
                Patient demographics were similar for age, sex, cardiopulmonary bypass pump time, cross clamp time, surgical time, preoperative haemoglobin, coagulation profile, and the number of valves replaced during surgery. Tranexamic acid administration reduced intraoperative blood loss [median (range)] from 1656 (575-6270) to 720 ml (355-5616) (P < 0.01) and postoperative blood loss from 1170 (180-4025) to 538 ml (135-1465) (Intent to Treat n = 41, P < 0.01). The total red blood cells transfused (median, range) was reduced from 1500 (0-9300) ml to 480 (0-2850) ml (P < 0.01) in the TA group. In hospital complications and mortality rates were not reduced in the TA group.
                Tranexamic acid reduced blood loss and the need for blood product transfusion and appears to be an effective treatment for patients undergoing reoperative cardiac valvular surgery. The effects of 2-dosage regimens of tranexamic acid (10 mg/kg and 15 mg/kg) on blood loss and transfusion requirement were compared to saline placebo in 60 patients undergoing concurrent bilateral total knee arthroplasty, with additional reinfusion autotransfusion from intraarticular drains. Mean blood loss was 462 mL in 15 mL/kg group, 678 mL in 10 mg/kg group, and 918 mL in controls (P < .01 vs 15 mg/kg). Blood available for autotransfusion was greatest in controls and least in 15 mg/kg group. Combined autologous and allogenic transfusion volumes were similar in the treatment groups and significantly less than controls (P < .01). With use of an autologous reinfusion strategy, the lower dose is sufficient to lead to a lesser allogenic transfusion requirement.
                Copyright © 2011 Elsevier Inc. All rights reserved. Aprotinin has been used to decrease blood loss with complicated cardiac surgery but has not been investigated in extrapleural pneumonectomy, an operation that does not use cardiopulmonary bypass. In this prospective, randomized, placebo-controlled, double-blind trial, the authors investigated whether aprotinin decreased blood loss in patients who underwent this operation.
                After appropriate statistical design and institutional review board approval, eligible patients who were scheduled for extrapleural pneumonectomy were randomized to receive either aprotinin or placebo during the operation. Blood loss and survival data were obtained from electronic medical records and surgical databases.
                Of 20 patients who were enrolled, 16 patients met criteria for blood loss analysis. Four patients were excluded from the blood loss analysis: Three patients were inoperable because of tumor spread and underwent limited surgery, and 1 patient died intraoperatively because of acute, massive hemorrhage. The mean blood loss was 769 mL with aprotinin versus 1832 mL with placebo (P = .05; Wilcoxon test). All 20 patients were included in survival analyses. All 9 patients who received placebo died. In contrast, 7 of 11 patients who received aprotinin remained alive at the time of the current report. Kaplan-Meier survival curves differed significantly between the 2 groups (P = .0004). A Bayesian multivariate survival analysis of 18 patients who had complete data available on 8 prognostic variables indicated a posterior probability of .99 that aprotinin was beneficial.
                Aprotinin decreased blood loss. After accounting for covariate effects, there was a significant comparative benefit with aprotinin in postoperative survival. This finding was unexpected and could not be considered conclusive because of the small size of the current study. A confirmatory study may be warranted.
                (c) 2009 American Cancer Society. Large doses of aprotinin (1,000,000-2,000,000 kallikrein inhibitor units [KIU] initial dose and a 500,000 KIU/h infusion) have been used during orthotopic liver transplantation (OLT) to reduce the incidence and severity of fibrinolysis. This double-blinded study was designed to investigate whether a small-dose infusion of aprotinin (200,000 KIU/h) would control fibrinolysis. A controlled study was undertaken to compare small-dose aprotinin with a placebo in patients undergoing OLT with veno-venous bypass. Forty-four patients were randomized either to the aprotinin group (n = 21), which received an intravenous infusion of 200,000 KIU/h without an initial dose, or to a control group (n = 23), which received normal saline. Coagulation variables, thrombelastograms, and postoperative blood drainage were measured. Blood levels of fibrin degradation products (FDP) were significantly higher in the control group (95% > 20 micrograms/mL) at the end of surgery compared to the aprotinin group (53% > 20 micrograms/mL, P < 0.01). The transfusion of cryoprecipitate units was more in the control group versus the aprotinin (12.6 +/- 12.8 vs 5.7 +/- 7.5; P < 0.04), as was the number of fresh frozen plasma units (6.6 +/- 3.5 vs 3.6 +/- 6.1; P < 0.05). We conclude that an infusion of a small dose of aprotinin can safely control fibrinolysis during liver transplantation with a concomitant reduction in transfusion of blood products. Intraoperative administration of the proteinase inhibitor aprotinin causes reduction in blood loss and homologous blood requirement in patients undergoing cardiac surgery. To ascertain the blood-saving effect of aprotinin and to obtain further information about the mode of action, 40 patients undergoing primary myocardial revascularization were randomly assigned to receive either aprotinin or placebo treatment. Aprotinin was given as a bolus of 2 x 10(6) kallikrein inactivator units (KIU) before surgery followed by a continuous infusion of 5 x 10(5) KIU/h during surgery. Additionally, 2 x 10(6) KIU were added to the pump prime. Strict criteria were used to obtain a homogeneous patient selection. Total blood loss was reduced from 1,431 +/- 760 ml in the control group to 738 +/- 411 ml in the aprotinin group (P less than 0.05) and the homologous blood requirement from 838 +/- 963 ml to 163 +/- 308 ml (P less than 0.05). In the control group, 2.3 +/- 2.2 U of homologous blood or blood products were given, and in the aprotinin group, 0.63 +/- 0.96 U were given (P less than 0.05). Twenty-five percent of patients in the control group and 63% in the aprotinin group did not receive banked blood or homologous blood products. The activated clotting time as an indicator of inhibition of the contact phase of coagulation was significantly increased before heparinization in the aprotinin group (141 +/- 13 s vs. 122 +/- 25 s) and remained significantly increased until heparin was neutralized after cardiopulmonary bypass (CPB).(ABSTRACT TRUNCATED AT 250 WORDS) Aprotinin, a hemostatic agent, regulates fibrinolysis, modulates the intrinsic coagulation pathway, stabilizes platelet function, and exhibits anti-inflammatory properties through inhibition of serine proteases, such as trypsin, plasmin, and kallikrein. Aprotinin has been used successfully for many years in cardiac operations, and there have been preliminary investigations of its use in hip replacement operations. The objectives of this multicenter, randomized, placebo-controlled, double-blind trial were to evaluate the efficacy and safety of aprotinin as a blood-sparing agent in patients undergoing an elective primary unilateral total hip replacement and to examine its effect on the prevalence of deep-vein thrombosis in this population.
                Seventy-three patients received a placebo; seventy-six patients, a low dose of aprotinin (a load of 500,000 kallikrein inhibitor units [KIU]); seventy-five, a medium dose of aprotinin (a load of 1,000,000 KIU, with infusion of 250,000 KIU per hour); and seventy-seven patients, a high dose of aprotinin (a load of 2,000,000 KIU, with infusion of 500,000 KIU per hour). The end points for the determination of efficacy were transfusion requirements and blood loss. Patients received standard prophylaxis against deep-vein thrombosis and underwent compression ultrasonography with color Doppler imaging of the proximal and distal venous systems of both legs to evaluate for the presence of deep-vein thrombosis.
                Aprotinin reduced the percentages of patients who required any form of blood transfusion (47 percent of the patients managed with a placebo needed a transfusion compared with 28 percent of those managed with low-dose aprotinin [p = 0.02],27 percent of those managed with high-dose aprotinin [p = 0.008], and 40 percent of those managed with medium-dose aprotinin [p = 0.5]). Only 6 percent (twelve) of the 212 patients treated with aprotinin required allogeneic blood compared with 15 percent (ten) of the sixty-eight patients treated with the placebo (p = 0.03). Aprotinin decreased the estimated intraoperative blood loss (p = 0.02 for the low-dose group, p = 0.04 for the medium-dose group, and p = 0.1 for the high-dose group), the measured postoperative drainage volume (p = 0.4 for the low-dose group, p = 0.006 for the medium-dose group, and p = 0.000 for the high-dose group), and the mean reduction in the hemoglobin level on the second postoperative day (thirty-four grams per liter for the placebo group, twenty-eight grams per liter for the low-dose group [p = 0.000], twenty-six grams per liter for the medium-dose group [p = 0.000], and twenty-three grams per liter for the high-dose group [p = 0.0001). The rate of deep-vein thrombosis was similar for all groups.
                We concluded that aprotinin is safe and effective for use as a hemostatic agent in primary unilateral total hip replacements. In patients who are at high risk of receiving allogeneic blood, use of aprotinin may be of particular clinical and economic benefit. The effect of the proteinase-inhibitor aprotinin on blood loss and homologous blood requirement in cardiac surgery was investigated. In a prospective study, 902 adult patients were treated with high-dose aprotinin (total greater than 5 x 10(6) kallikrein inactivator units [KIU]; group A), while 882 patients without aprotinin administration served as the controls (group C). Both groups were operated on between January 1987 and October 1989, and included patients with primary coronary artery bypass grafting (n = 525 group C, n = 560 group A), valve replacement (n = 292 group C, n = 264 group A), or combined procedures (n = 65 group C, n = 78 group A), as well as cardiac reoperations (n = 91 group C, n = 110 group A). The average blood loss 36 hours postoperatively in the aprotinin group was 679 +/- 419 mL, compared with 1,038 +/- 671 mL in the control group (P less than 0.05). Total homologous blood requirement was also significantly less in group A (942 +/- 1,630 mL) compared with group C (1,999 +/- 2,283 mL) (P less than 0.05), a reduction of 53%. Serum creatinine concentrations did not show intergroup differences on the first postoperative day (group A, 1.2 +/- 0.7; group C, 1.3 +/- 0.5 mg/dL) or on discharge from the intensive care unit (ICU). Thus, impairment of renal function as a consequence of aprotinin treatment was not observed. Three patients developed signs of mild circulatory depression after injection of aprotinin, which responded promptly to vasopressor therapy.(ABSTRACT TRUNCATED AT 250 WORDS) Aprotinin causes a prolongation of the celite-activated clotting time (CACT), but not of the kaolin-activated clotting time (KACT). Therefore, concern has been raised regarding the reliability of CACT to monitor anticoagulation in the presence of aprotinin. The current study was designed to test the efficacy of aprotinin to improve anticoagulation, and to investigate whether the prolongation of CACT reflects true anticoagulation or is an in vitro artifact. To elucidate this antithrombotic effect of aprotinin, this study was done in patients prone to reduced intraoperative heparin sensitivity.
                In a prospective, randomized, double-blind clinical trial, 30 male patients scheduled for elective primary coronary revascularization and treated with heparin for at least 10 days preoperatively, received either high-dose aprotinin (group A) or placebo (group C). The CACT and KACT were determined, but only CACT was used to control anticoagulation with heparin. Parameters of coagulation that are indicators of thrombin generation and activity (F1+2 prothrombin fragments, thrombin-antithrombin III complex, and fibrin monomers), parameters of fibrinolysis (D-dimers), aprotinin, and heparin plasma concentrations were measured. Postoperative blood loss and allogeneic blood transfused were recorded.
                Total heparin administered was 36,200 units (95% confidence interval: 31,400-41,000; group C) compared with 27,700 (25,500-29,800) units (group A; P < 0.05). Hemostatic activation during cardiopulmonary bypass (CPB) was significantly reduced in group A compared with group C. After 60 min of CPB, all parameters were significantly different (P < 0.05) between the groups (group C vs. group A): F1+2 prothrombin fragments, 9.7 (8.9-11.7) ng/ml versus 7.5 (6.2-8.6) ng/ml; thrombin-anti-thrombin III complex (TAT), 53 (42-68) ng/ml versus 29 (23-38) ng/ml; and fibrin monomers, 23 (12-43) ng/ml versus 8 (3-17) ng/ml. Fibrinolysis was also attenuated; D-dimers at the end of operation were 656 (396-1,089) and 2,710 (1,811-4,055) ng/ml for groups A and C, respectively (P < 0.05). The CACT 5 min after the onset of CPB was 552 (485-627) versus 869 (793-955) s for groups C and A, respectively (P < 0.05), whereas the KACT showed no differences between the groups (569 [481-675] vs. 614 [541-697] s for groups C and A, respectively; P = NS). The 24-h blood loss was 1,496 (1,125-1,995) versus 597 (448-794) ml for groups C and A, respectively (P < 0.05).
                Aprotinin treatment in combination with heparin leads to less thrombin generation during CPB. Aprotinin has anticoagulant properties. Celite-activated ACT is reliable for monitoring anticoagulation in the presence of aprotinin, because the prolonged CACT in the aprotinin group reflects improved anticoagulation. Kaolin-activated ACT does not reflect this effect of aprotinin. To determine whether two low-dose regimens of aprotinin influence platelet function.
                Prospective, randomized, single-blinded trial.
                University teaching hospital performing 600 cardiac operations per year.
                Fifty-nine patients scheduled for cardiac surgery undergoing cardiopulmonary bypass (CPB) of expected duration of 60 minutes or more.
                Patients were randomized into three groups. Group C (control) included 21 patients who did not receive aprotinin. In group A2, 17 patients received 14,286 kallikrein inhibitor units (KIU)/kg (2 mg/kg) of aprotinin before surgery, followed by a continuous infusion of 7,143 KIU/kg/h (1 mg/kg/h) until the end of surgery. In group A4, 19 patients received 28,572 KIU/kg (4 mg/kg) of aprotinin before surgery, followed by the same infusion.
                Postoperative bleeding and transfusion requirements were significantly less in group A4. Changes in platelet number and function were similar in the three groups. Platelet aggregation was assessed in four periods: before CPB (T1), post-CPB (T2), and 2 hours (T3) and 4 hours (T4) after CPB. Platelet aggregation induced by adenosine diphosphate, 1 and 2 micromol/L; ristocetin, 1 mg/mL; and arachadonic acid (AA), 1.4 mmol/L, decreased at T2 (p < 0.001) in all groups, and for the ristocetin and AA groups, remained at less than baseline values at T3 and T4. In five patients from each group, platelet receptors for glycoprotein IIb-IIIa (GPIIb-IIIa) and expression of platelet activation markers, guanosine monophosphate 140 (GMP-140) and lysosomal protein, were measured by flow cytometry before and after CPB. Modifications in the expression of GPIIb-IIIa were always modest and without statistical significance. Platelet activation markers, GMP-140 or lysosomal protein, nearly doubled from baseline to post-CPB only in the A4 group, whereas they remained stable in both other groups (statistically not significant).
                The two regimens of aprotinin, both considered low dosage, did not exert a protective effect on platelet function. Neither dose produced changes in platelet GPIIb-IIIa or platelet activation markers. However, bleeding and transfusion needs were decreased. Epsilon-aminocaproic acid (epsilon-ACA), an antifibrinolytic agent, is used in cardiac surgery to decrease postoperative bleeding. Theoretical concerns exist about the potential for epsilon-ACA to contribute to thrombotic complications. For this reason epsilon-ACA administration is sometimes delayed until after heparinization. This study investigated the impact of the timing of epsilon-ACA administration on its efficacy.
                In this double-blind study, 90 patients undergoing primary coronary artery bypass graft surgery were prospectively randomized to receive either epsilon-ACA commencing prior to skin incision (bolus 150 mg/kg, followed by an infusion at 15 mg x kg(-1) x hr(-1), epsilon-ACA commencing after heparin (same doses), or placebo. All infusions were terminated at the end of cardiopulmonary bypass. Criteria for the transfusion of blood products were standardized. Postoperative chest tube drainage (at 6 h, 12 h, and at chest tube removal) and blood transfusion requirements of the three groups were compared.
                At all time intervals, the placebo group had significantly greater chest tube drainage than either of the two epsilon-ACA groups (P < 0.005). At no time did a significant difference exist between the two epsilon-ACA groups. A trend existed for the placebo group to require more blood products than either epsilon-ACA group.
                Epsilon-ACA produces a reduction in chest tube drainage in patients undergoing primary coronary artery bypass graft surgery. This effect is similar whether the drug is given prior to incision or following anticoagulation. Given the similar hemostatic efficacy and the theoretical potential for thrombotic complications, it may be prudent to administer epsilon-ACA following anticoagulation. The proteinase inhibitor aprotinin is used in open heart surgery to reduce intraoperative and postoperative blood loss and transfusion requirements. To investigate a possible influence on graft patency, a randomized double-blind group comparison study was carried out in male patients elected for primary bypass surgery. One hundred ten (55/55) patients received either placebo treatment or aprotinin according to the Hammersmith scheme (2 Mio KIU as loading dose before sternotomy, followed by an infusion of 0.5 Mio KIU/h until the end of surgery; 2 Mio KIU added to the priming volume additionally). Graft patency was evaluated by angiography in 44 aprotinin and 35 placebo patients between the 18th and 35th days postoperatively. There was no difference in the overall graft occlusion: in the aprotinin group 89.5% (111/124) grafts were found patent compared to 87.2% (89/102) in the placebo group. Of the aprotinin patients 72.7% (32/44) and 71.4% (25/35) of the placebo patients had all grafts patent. Venous grafts were occluded in 16% (7/44) of aprotinin patients and in 29% (10/35) of placebo patients. On the other hand 5/27 patients in the aprotinin group vs 0/27 in the placebo group had occluded internal mammary artery (IMA) grafts (P = 0.0511%). Graft occlusions were not accompanied by signs of myocardial infarction in any case. Fifty-one patients in the aprotinin group and 47 patients in the placebo group were valid for parameters of clinical efficacy: blood loss within 6 h postoperatively was reduced by 58.5% in the aprotinin group (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) We sought to evaluate the effectiveness of tranexamic acid in off-pump coronary artery bypass grafting surgery, either when used in combination with mechanical cell salvage or when used alone.
                One hundred patients were randomized to either 2 g of tranexamic acid as an intravenous bolus before sternotomy or to placebo. Intraoperative and postoperative cell salvage was used in all patients. The primary end point was early postoperative blood loss (within 4 hours). To evaluate the efficacy of tranexamic acid in isolation, we also performed a meta-analysis of 4 randomized trials identified from a systematic literature search. The primary end point of the meta-analysis was red cell transfusion.
                In our randomized trial patients in the tranexamic acid group had a significant reduction in early postoperative blood loss, (median difference, 50 mL; 95% confidence interval, 15-100 mL; P < .01); however, there was no reduction in the frequency of blood component transfusion. Patients in the placebo group received a significantly larger volume of autotransfused red cells (median difference, 120 mL; 95% confidence interval, 0-220 mL; P = .02). The meta-analysis demonstrated a significant reduction in red cell transfusions in patients receiving tranexamic acid compared with those receiving placebo (risk ratio, 0.48; 95% confidence interval, 0.24-0.97; P = .041). There was also a reduction in the frequency of any allogeneic blood component transfusion, as well as a highly significant reduction in postoperative blood loss, in patients receiving tranexamic acid (P < .001).
                Tranexamic acid reduces blood loss and transfusion requirements in off-pump coronary artery bypass grafting surgery. A reduction in allogeneic blood transfusion was not evident in the presence of perioperative cell salvage. These data support the routine use of tranexamic acid in off-pump coronary artery bypass grafting surgery. The administration of tranexamic acid (TA) prior to cardiopulmonary bypass (CPB) has been associated with reduced bleeding during and after cardiac surgery. In a prospective, randomized, controlled, double-blind clinical trial, adult patients undergoing repeat open heart surgery received TA (n = 17) or an equal volume of saline placebo (n = 13). In the TA group, a 20-mg/kg intravenous (IV) initial dose of TA at akin incision was followed by an infusion of 2 mg.kg-1.h-1, which continued for the duration of the surgical procedure. Identical transfusion guidelines were followed in both groups. Routine coagulation tests, D-dimer levels, mediastinal tube drainage, and transfusion requirements were compared. Cumulative postoperative mediastinal tube drainage measured at 24 h was 649 +/- 391 mliter (mean +/- SD) in the TA group compared with 923 +/- 496 mliter in the placebo group (P < 0.01). Forty-eight-and 72-h mediastinal tube drainage were also significantly less in the TA group (P < 0.01). Seven of 17 TA patients received to transfusion of allogeneic blood products compared with 1 of 13 placebo patients (P = 0.047). The incidence and volumes of platelet and fresh frozen plasma transfusion in the TA group were not significantly different in comparison with the placebo group. The perioperative increase in D-dimer levels (post-CPB minus pre-CPB) in the placebo group (median difference = 675 ng/mliter, range 125-1648) was significantly more than in the TA group (median difference = 182 ng/mliter, range -426-1950; P = 0.003). Sternal closure occurred in 41 +/- 21 min in the TA group and 61 +/- 49 min in the placebo group (P = 0.14), and the subjective bleeding score was less in the TA group than in the placebo group (2.38 +/- 0.78 vs 3.08 +/- 1.04; P = 0.045). The data from the current study support the prophylactic use of TA in patients undergoing repeat cardiac surgery. TA administered prior to CPB reduced the incidence of allogeneic transfusions and postoperative mediastinal tube drainage, and improved the subjective assessment of post-CPB hemostasis in a group of patients at moderately high risk for perioperative bleeding. The objective of this study was to study the effect of low-dose tranexamic acid (TA) on postoperative bleeding and coagulation variables after coronary artery bypass grafting operation.
                Fifty patients undergoing primary coronary artery bypass grafting were randomly assigned to receive either placebo (0.9% NaCl; n = 25) or 10 mg/kg TA followed by infusion of 1 mg/kg per hour during the operation (n = 25). Data measured included blood loss, transfusion, reoperation, fibrinogen level, fibrinogen split products, platelet size, and platelet function. Measurements were made after induction of anesthesia, after heparin administration, during patient warming, after skin closure, and 24 hours after operation.
                Patients in the TA study group weighed less. Other demographic characteristics were similar between groups. Postoperative bleeding was less in the TA group (194 +/- 135 mL versus 488 +/- 238 mL, p < 0.001), whereas blood requirement was higher in the control group (1.68 +/- 1 versus 0.52 +/- 0.9 U of packed cells per patient, p < 0.001). The percent of patients exposed to blood products was significantly less in the TA group (36% versus 100%, p < 0.001). Fibrinogen split products were lower in the TA group during bypass (p < 0.001). Fibrinogen levels fell in both groups during cardiopulmonary bypass. Platelet number and function were reduced equally in both groups by cardiopulmonary bypass. Other test results were not different between groups.
                The use of low-dose TA during coronary artery bypass grafting significantly reduced the coagulopathy-induced postoperative bleeding and allogeneic blood products requirement. The low levels of fibrinogen split products during bypass in the study group reflect the inhibiting effect of TA in fibrinolysis. Tranexamic acid had no effect on platelet function during cardiopulmonary bypass. Patients with end-stage liver disease frequently incur large-volume blood loss during liver transplantation associated with mechanical factors, preexisting coagulopathy, and intraoperative fibrinolysis.
                Between April 1992 and May 1994, the authors of this double-blind, randomized, placebo-controlled study examined the effect of high-dose tranexamic acid (maximum of 20 g) on blood loss and blood product requirements in patients undergoing primary isolated orthotopic liver transplantation. Primary outcome measures were volume of blood loss (intraoperative blood loss and postoperative drainage) and erythrocyte, plasma, platelet, and cryoprecipitate use during surgery and the first 24 h of intensive care unit stay.
                Patients receiving tranexamic acid (n = 25) had less intraoperative blood loss (median, 4.3 l; interquartile range, 2.5 to 7.9; P = 0.006) compared with the placebo group (n = 20; median, 8 l; interquartile range, 5 to 15.8), and reduced intraoperative plasma, platelet, and cryoprecipitate requirements. Median perioperative erythrocyte use was 9 units (interquantile range, 4 to 14 units) in patients receiving tranexamic acid and 13 units (interquantile range, 7.5 to 31 units) in controls (P = 0.03). Total perioperative donor exposure was 20.5 units (interquantile range, 16 to 41 units) in patients receiving tranexamic acid and 43.5 units (interquantile range, 29.5 to 79 units) in controls (P = 0.003). Results for postoperative wound drainage were similar. Hospital stay and need for retransplantation were comparable in both groups. No patient in either group showed clinical evidence of hepatic artery or portal venous thrombosis within 1 month of transplantation.
                High-dose tranexamic acid significantly reduces intraoperative blood loss and perioperative donor exposure in patients with end-stage parenchymal liver disease who are undergoing orthotopic liver transplantation, with marked reductions in platelet and cryoprecipitate requirements. The great risk of severe infectious diseases transmission through blood transfusion, has increased during the last years the effort to reduce the bank blood and its derivates use. Many techniques have proposed to achieve this purpose during and post cardiopulmonary bypass: normovolemic hemodilution, perioperative blood autotransfusion, postoperative return of extra corporeal circuit and chest drains blood and the particular use of some drugs. In the last few years several reports have been presented in the literature concerning the reduction of intra and postoperative bleeding in cardiac surgery by high dose Aprotinin administration. A randomized study with the use of this pharmacologic agent is presented: a group of patients was treated with Aprotinin (shared in two subgroups receiving respectively a different dose of the drug) and a control group. The results were highly encouraging both because of the reduction of peri and postoperative bleeding and because of the bank blood use important reduction. Total knee arthroplasty (TKA) is often carried out using a tourniquet and shed blood is collected in drains. Tranexamic acid decreases the external blood loss. Some blood loss may be concealed, and the overall effect of tranexamic acid on the haemoglobin (Hb) balance is not known.
                Patients with osteoarthrosis had unilateral cemented TKA using spinal anaesthesia. In a double-blind fashion, they received either placebo (n=24) or tranexamic acid 10 mg kg(-1) (n=27) i.v. just before tourniquet release and 3 h later. The decrease in circulating Hb on the fifth day after surgery, after correction for Hb transfused, was used to calculate the loss of Hb in grams. This value was then expressed as ml of blood loss.
                The groups had similar characteristics. The median volume of drainage fluid after placebo was 845 (interquartile range 523-990) ml and after tranexamic acid was 385 (331-586) ml (P<0.001). Placebo patients received 2 (0-2) units and tranexamic acid patients 0 (0-0) units of packed red cells (P<0.001). The estimated blood loss was 1426 (1135-1977) ml and 1045 (792-1292) ml, respectively (P<0.001). The hidden loss of blood (calculated as loss minus drainage volume) was 618 (330-1347) ml and 524 (330-9620) ml, respectively (P=0.41). Two patients in each group developed deep vein thrombosis.
                Tranexamic acid decreased total blood loss by nearly 30%, drainage volume by approximately 50% and drastically reduced transfusion. However, concealed loss was only marginally influenced by tranexamic acid and was at least as large as the drainage volume. To assess the relative efficacy of tranexamic acid compared with a control group to decrease bleeding and transfusion requirements in a uniform population undergoing aortic valve replacement.
                Prospective, randomized, double-blind study.
                University hospital.
                Adult cardiac surgery patients (n = 300).
                Patients were randomized into 2 groups to receive either a total of 5 g of tranexamic acid or a saline solution. Bleeding in the postoperative period, transfusions of bank blood products, coagulation profile, intensive care unit stay, and hospital length of stay were recorded.
                Postoperative bleeding in patients treated with tranexamic acid was significantly lower compared with the control group (p < 0.0001). Packed red blood cells and fresh frozen plasma usage were reduced in the tranexamic acid group compared with the control group (p = 0.0095 and p < 0.0001). Only 24.5% of tranexamic acid patients received blood products versus 45% of control patients (p < 0.01). There was no significant difference in hematologic and coagulation profiles after the operation between the groups.
                Tranexamic acid reduces postoperative blood loss and transfusion requirements in elective aortic valve replacement.
                Copyright 2001 by W.B. Saunders Company. Patients having cardiac operations often require blood transfusions. Aprotinin reduces the need for blood transfusions during coronary artery bypass graft operations. To determine the safety and effectiveness of aprotinin in reducing the use of allogeneic blood and postoperative mediastinal chest tube drainage, we studied 212 patients undergoing primary sternotomy for valve replacement or repair.
                This study was multicenter, randomized, prospective, double-blind, and placebo-controlled. Patients received high-dose aprotinin (n = 71), low-dose aprotinin (n = 70), or placebo (n = 71). The study medication was given as a loading dose followed by a continuous infusion and pump prime dose. Heparin administration was standardized. Transfusions, postoperative mediastinal shed blood, and adverse events were tracked.
                Demographic profiles were similar among the treatment groups. Aprotinin did not decrease the percentage of patients receiving transfusions when compared with placebo (high-dose aprotinin, 63%, p = 0.092; low-dose aprotinin, 52%, p = 0.592; placebo, 48%). Aprotinin was associated with a reduction in the volume of mediastinal shed blood (high-dose aprotinin vs placebo, p = 0.002; low-dose aprotinin vs placebo, p = 0.017). Adverse events were equally distributed among the treatment groups except for postoperative renal dysfunction (high-dose aprotinin, 11%; low-dose aprotinin, 7%; placebo, 0%; p = 0.01). A disproportionate number of patients in the high-dose aprotinin group with postoperative renal dysfunction also had diabetes mellitus.
                Aprotinin treatment in this population did not reduce allogeneic blood use, although there were significant reductions in the volume of mediastinal shed blood. Although low-dose aprotinin administered after cardiopulmonary bypass has been reported to reduce mediastinal blood loss and blood product requirements in patients not taking aspirin, it is unknown whether low-dose postoperative aprotinin has any beneficial effects in patients undergoing coronary artery bypass operations who are at high risk of excessive postoperative bleeding and increased transfusion requirements because of aspirin use until just before the operation.
                Fifty-five patients undergoing primary coronary artery operations with cardiopulmonary bypass who continued taking aspirin (150 mg/d) until the day before the operation were enrolled in a prospective, randomized, double-blind trial to receive a single dose of either placebo (n = 29) or 2 x 10(6) kallikrein inhibiting units of aprotinin (n = 26) at the time of sternal skin closure.
                Patients in the aprotinin group had a lower rate (28 +/- 18 vs 43 +/- 21 mL/h [mean +/- standard deviation], P <.005) and total volume of mediastinal drainage (955 +/- 615 vs 1570 +/- 955 mL, P <.007), as well as a shorter duration of mediastinal drain tube insertion (24.4 +/- 13.8 vs 31.3 +/- 16.5 hours, P <.05). In addition, a smaller proportion of patients receiving aprotinin required a blood product (31% vs 62%, P =.03), resulting in a reduction in the use of packed cells by 47% (P =.05), platelets by 77% (P =.01), fresh frozen plasma by 88% (P =.03), and total blood products by 68% (P =.01) in this group.
                These results suggest that postoperative administration of low-dose aprotinin in patients taking aspirin until just before primary coronary artery operations with cardiopulmonary bypass not only reduces the rate and total amount of postoperative mediastinal blood loss but also lowers postoperative blood product use. Thirty-eight patients undergoing a cardiac operation randomly received either tranexamic acid, a potent inhibitor of plasminogen, or placebo in an effort to determine whether prophylactic antifibrinolytic therapy reduces chest tube drainage. Twelve-hour blood loss was 750 +/- 314 (standard deviation) ml in the placebo group and 496 +/- 228 ml in the drug group (p = 0.0057). Fibrin split products were present more frequently in patients in the placebo group (17 of 20 compared with four of 18 in the drug group; p = 0.0002). Tranexamic acid markedly decreased plasminogen availability (112 +/- 104 units in the placebo group versus 36 +/- 18 units in the drug group, p = 0.0058). Plasma fibrinogen concentrations were similar in the placebo and drug groups. Patients in the placebo group received more fresh-frozen plasma and more mediastinal shed blood than those in the drug group. No coagulation-related complication occurred in the group receiving tranexamic acid. We conclude that prophylactic tranexamic acid can be administered safely to inhibit fibrinolysis during cardiac operations, decrease postoperative bleeding, and possibly decrease the frequency of blood product transfusion. Bleeding during the first 24 hours following cardiac surgery using cardio-pulmonary bypass (CPB) is a serious complication. Attempts to modify the degree of postoperative bleeding with pharmacologic therapy have met with limited success. Tranexamic acid, a potent inhibitor of plasminogen, may decrease the amount of mediastinal bleeding following surgery utilizing CPB. We assigned 30 patients who were about to undergo cardiac surgery to a double-blind randomized trial. The treatment group received tranexamic acid, given intravenously as 10 mg/kg over 30 minutes, at the time of skin incision, followed by a 1 mg/kg/hr infusion for 12 hours. The control group received a placebo (saline) of equal volume. Measurements of shed mediastinal blood and transfused homologous blood were made at 6, 12, and 24 hours postoperatively. Mediastinal blood loss in the treatment and control groups was 382 mL versus 594 mL at 6 hours (P = 0.08), 502 mL versus 848 mL at 12 hours (P = 0.04), and 711 mL versus 1160 mL at 24 hours (P = 0.02). The mean transfusion volumes after 24 hours were 356 mL in the treatment group and 528 mL in the placebo group (P = NS). Prophylactic tranexamic acid infusion decreases mediastinal blood loss following cardiopulmonary assisted cardiac surgery. nan High-dose aprotinin is an effective but costly method to reduce transfusions after cardiopulmonary bypass (CPB). Very low doses of aprotinin have been shown to be effective in primary cardiac surgery, but not in patients undergoing procedures associated with the greatest usage of allogeneic blood products after CPB. We evaluated the efficacy of ultra-low-dose aprotinin in this patient population.
                Aprotinin 1 million KIU or placebo was added to the priming solution of the CPB circuit of 52 patients undergoing a reoperation and/or a complex surgical procedure. Dryness of operative field, hemoglobin concentrations, coagulation parameters, chest drainage, and transfusion requirements were compared.
                Total chest drainage was not different between groups, but fewer patients in the aprotinin group required additional protamine postoperatively (35% vs 69% for controls, p = 0.03) and fewer received fresh frozen plasma (FFP; 19% vs 46% for controls, p = 0.04). Red cell transfusion was smaller in the aprotinin group compared to placebo (median 4 and 2 units, respectively, p = 0.04). Transfusion of FFP, platelets, cryoprecipitates was not different between groups. Total number of units transfused tended to be reduced in the aprotinin group compared to control (median 2 and 7 units, respectively, p = 0.06).
                Prophylactic administration of ultra-low-dose aprotinin reduced transfusions in patients undergoing repeat operations or complex procedures. Aprotinin could be used in a more economical manner, even in this patient population at high-risk of receiving allogeneic blood products. The effect of high dose aprotinin (Trasylol) was evaluated in three groups of patients undergoing cardiopulmonary bypass. In a prospective, placebo-controlled, double-blind study, 80 patients having primary aorta-coronary bypass grafting received aprotinin (700 mg approximately) or saline placebo from the beginning of the procedure until skin closure. Standardized anesthetic, perfusion, and surgical techniques were used. The total loss from the thoracic drains was significantly reduced in the aprotinin group as compared with the loss in the placebo group (309 +/- 133 ml versus 573 +/- 166 ml, p less than 0.01; mean +/- standard deviation). There was a threefold difference in the total hemoglobin loss into the chest drains (aprotinin 12.0 +/- 12.6 gm versus placebo 37.7 +/- 18.3 gm). Patients of the aprotinin group received remarkably less bank blood postoperatively: 13 units total compared with 75 units. Of the 40 patients in the aprotinin group, 32 received no bank blood compared with 2 of 37 patients in the placebo group. Venous hemoglobin levels preoperatively, on day 1, and on day 7 postoperatively did not differ between the groups. At day 7 the values were 13.1 +/- 1.4 gm/dl versus 12.5 +/- 1.2 gm/dl in the aprotinin group and the placebo group, respectively. Platelet counts determined at fixed times perioperatively did not differ between the two groups. In contrast, template bleeding time measured in 32 study patients was distinctly different between groups, with a postoperative rise of 6.2 +/- 2.1 minutes in the placebo group opposed to only 1.5 +/- 1.1 minutes in the aprotinin group.(ABSTRACT TRUNCATED AT 250 WORDS) We evaluated the effects of tranexamic acid (TA) administered before and after cardiopulmonary bypass (CPB) in a prospective, randomized, placebo-controlled, double-blind study of adult patients undergoing primary coronary artery bypass grafting surgery. Patients received placebo (n = 30) or TA 15 mg/kg before CPB, followed by a TA infusion of 1 mg x kg(-1) x h(-1) for 5 h (n = 30) or TA 15 mg/kg after CPB, followed by a TA infusion of 1 mg x kg(-1) x h(-1) for 5 h (n = 30). Demographic, medical, surgical, laboratory, mediastinal chest tube drainage (MCTD), hemoglobin loss, transfusion, and outcome data were collected. Allogenic blood product administration was tightly controlled. The demographic, medical, and surgical characteristics were similar in all three groups. The median postoperative MCTD and hemoglobin loss in the pre-CPB TA group (710 mL, 8.6 g) was significantly less (P < 0.001) compared with the control (1202 mL, 44.2 g) and post-CPB TA groups (1020 mL, 23.4 g). The percentage of patients who received no allogenic blood products was 27% for the pre-CPB TA group and 33% for the post-CPB TA group (not significant). These percentages were significantly lower than those in the placebo group (66%, P < 0.001). The median number of allogenic blood products administered to the pre-CPB TA group (0 units) was significantly less compared with the control group (4.5 units). The thromboelastogram and fibrinogen split product levels in the pre-CPB TA group indicated better platelet function and less activation of the fibrinolytic system compared with the other two groups (P < 0.05). There were no intergroup differences in reoperation, myocardial infarction, stroke, infections, or death. These data support the use of pre-CPB TA to decrease patient exposure to postcardiopulmonary bypass allogenic blood products.
                In this randomized, placebo-controlled trial, we investigated the efficacy of tranexamic acid to decrease bleeding and blood transfusions after open-heart operations. Tranexamic acid administered before and during the operation was effective in decreasing both bleeding and transfusions. When tranexamic acid was administered immediately after the operation, it had a minor beneficial effect. Extensive blood loss related to knee arthroplasty is quite normal and many patients require blood transfusions. Surgery and the use of pneumatic tourniquets lead to an increase in the activity of the fibrinolytic system, which in turn may accentuate the blood loss. Drugs that inhibit the fibrinolytic system may thus be used to reduce blood loss. Tranexamic acid (TA) acts by binding to one of the enzymes at the start of the coagulation cascade, so inhibiting the fibrinolytic system. A concern is that this inhibition may have the side effect of increasing thromboembolic disease, a common complication of joint replacement surgery. We aimed to confirm the reductions in blood loss and to assess the impact of TA usage on clinical and sub-clinical DVT.
                We performed a prospective, randomised, double blind, controlled trial, using patients due to undergo primary unilateral total knee arthroplasty. Patients were randomised to receive either 15 mg/kg of tranexamic acid or a similar volume of normal saline at the time of cementing of the prosthesis. Perioperative blood loss was recorded and patients were screened for DVT with duplex ultrasound assessment of both legs on the fifth post-operative day.
                A statistically significant (p=0.006) decrease in blood loss in the early post-operative period was noted in the group receiving tranexamic acid. This was not associated with a significant difference in total blood loss (p=0.55) or in transfusion requirements. There was no of evidence in DVT in either group on duplex ultrasound screening of the lower limbs.
                One injection of 15 mg/kg of tranexamic given at the time of cementing the prosthesis in total knee arthroplasty, before deflation of the tourniquet, significantly decreases the amount of blood loss in the early post-operative period. The treatment was not associated with an increase in thromboembolic complications. Cardiac surgery involving cardiopulmonary bypass (CPB) leads to activation of the hemostatic/inflammatory system. We compared the influence of a half-dose aprotinin regimen on postoperative blood loss and the activation of the hemostatic/inflammatory system during CPB, when used during a heparin-level-based heparin management for cardiac surgery. Two-hundred patients (n = 100 in each group) were enrolled in this randomized prospective study. In Group I only heparin was given according to the results of the Hepcon HMS Plus. In Group II aprotinin was added with a bolus of 1 x 10(6) kallikrein inhibiting units (KIU) for the patient immediately before initiation of CPB, 1 x 10(6) KIU in the priming solution of the CPB, and a continuous infusion of 250,000 KIU/h during CPB. Postoperative blood loss was determined after 12 h. Heparin and antithrombin activity were evaluated by an anti-Xa assay and measurement of antithrombin III activity. Hemostatic activation was evaluated by adenosine diphosphate-stimulated platelet aggregometry and by measurements of the generation/release of beta-thromboglobulin (beta-TG), soluble P-selectin (sPS), thrombin (TAT), prothrombin 1 and 2 fragments (PTF1+2), factor XIIa (FXIIa), plasmin (PAP), and D-dimers. Inflammatory response was evaluated by measuring complement factors 5b-9 (C5b-9), interleukin (IL)-6, and neutrophil elastase (NE). There were no differences in the pre-CPB values or duration of CPB between the two groups. There were no differences in the post-CPB values for platelet count, platelet aggregation, beta-TG, sPS, TAT, PTF1+2, C5b-9, NE, or IL-6. The additional use of aprotinin resulted in a significant decrease of PAP, D-dimers, and 12 h postoperative blood loss, whereas generation of the contact factor XIIa was increased. The administration of aprotinin significantly reduced postoperative blood loss after cardiac surgery and CPB. This most likely has to be attributed to the antifibrinolytic effects of aprotinin. No effects on thrombin generation, platelet activation, inflammatory response, or clinical outcome were noted.
                The use of half-dose aprotinin and heparin-level-based anticoagulation management during cardiopulmonary bypass leads to a significant reduction of postoperative blood loss after cardiac surgery. This effect can most likely be attributed to the antifibrinolytic effects of aprotinin, as we did not observe effects on other variables of activation of the hemostatic/inflammatory system. Heart transplantation is associated with excessive bleeding due to recipient coagulopathy, frequent need for reoperative median sternotomy, and prolonged cardiopulmonary bypass. Aprotinin reduces bleeding and the inflammatory response after cardiopulmonary bypass, but there are concerns about efficacy and side effects.
                To determine the role of aprotinin in primary and reoperative sternotomy heart transplantation, we studied 70 patients undergoing heart transplantation between August 1993 and October 1994. Thirty-eight undergoing primary sternotomy for heart transplantation and receiving no aprotinin were randomized to group A (n = 20); patients in group B (n = 18) received the full recommended dose. Similarly, 32 patients undergoing reoperative heart transplantation were randomized to group C (n = 16), receiving no aprotinin, and to group D (n = 16), receiving aprotinin at the full recommended dose. All patients received the same immunosuppression regimen. Similarities in the groups included recipient age, weight, preoperative hemodynamic indices, creatinine, creatinine clearance, platelet count, hemoglobin, percentage receiving warfarin, prothrombin time, partial thromboplastin time, cardiopulmonary bypass time, and creatinine level at 48 hours.
                There were no significant differences postoperatively between groups A and B. Differences (p < 0.05) 24 hours postoperatively between groups C and D, respectively, included: total blood product requirement (5.9 +/- 3.8 versus 3.6 +/- 2.0 U), total fluid balance (+752 +/- 300 versus -250 +/- 185 mL), chest tube drainage (894 +/- 120 versus 526 +/- 95 mL), alveolar-arterial O2 difference (120.4 +/- 45.9 versus 95.5 +/- 33.5), and pulmonary artery mean pressures (28.2 +/- 4.6 versus 21.1 +/- 3.5 mm Hg).
                Aprotinin decreases bleeding after reoperative heart transplantation without renal dysfunction. Decreased inflammation is manifested as reduced fluid requirement and improved pulmonary and right heart function, which benefit patients during the posttransplantation period. Aprotinin at recommended doses is effective and safe for patients undergoing reoperative heart transplantation. Although the blood-saving effect of aprotinin has been well documented in cardiac surgery and lung transplantation, its use in lung surgery has received less attention. We present our experience with the intraoperative application of aprotinin in lung resections with a predicted high risk of bleeding.
                Thirty-eight patients undergoing major thoracic surgical procedures were randomized into treatment and placebo groups. The treatment group (n=18) received a bolus of 2 x 10(6) kallikrein inhibitor units (KIU) of aprotinin followed by 5 x 10(5) KIU/h during surgery. The placebo group (n=20) received an isotonic saline infusion instead.
                There was no significant difference between the groups concerning diagnosis, co-morbidity, age, sex, height, and weight. The mean intraoperative blood loss in the treatment group was significantly reduced (342 vs. 808 ml, P<0024), postoperative blood loss was also reduced (623 vs. 1282 ml, P<0.0007) and the need for blood transfusion was less (14 vs. 60, n.s.). No severe side effects of aprotinin were registered. Re-thoracotomy was necessary in two patients of the placebo group because of postoperative bleeding.
                Aprotinin reduces the perioperative blood loss and the need for blood transfusion in thoracic surgical procedures in patients with an increased risk of bleeding. As Aspirin (ASA) has proven efficacy in preventing patients with CAD from complications related to cardiovascular diseases, most patients scheduled for CABG are treated with ASA therapy. Consequently, impaired hemostasis is a problem in the management of CABG patients. Clinical studies have shown that Aprotinin can reduce bleeding and the use of blood products by 50% in patients both with and without pre-operative ASA therapy. Concerning the combined effect of peri-operative low-dose ASA therapy and intra-operative high-dose Aprotinin therapy, the gathering of additional and prospective data seemed to be necessary.
                We conducted a double-blind two-centre randomised three-arm study in patients with elective primary CABG surgery. Three groups have been tested, comprising 119 patients in total (group A: ASA + Aprotinin, group B: placebo + Aprotinin, group C: placebo + placebo) to investigate a possible reduction of bleeding in Aprotinin treated patients. For all patients, thromboxane levels were used to identify ASA or placebo treatment.
                The post-operative blood loss is significantly reduced by 21% after Trasylol administration (B vs. C; P = 0.009). The unexpected result of this study has been that the pre-treatment with ASA led to a further reduction of 18% (A vs. C; P < 0.0001). The difference between the two Aprotinin groups (A and B) is significant (P = 0. 01) in favour of ASA pre-treatment. Myocardial infarction (MI) had been diagnosed at levels of 1.8% in total (2/113), 2.6% (1/38) in group B and 3.2% (1/31 ) in group C. An additional blinded evaluation of ECG, enzyme levels and clinical status revealed 'definite, probable and possible' MIs of 5% in group A, compared to 16% in group B and 13% in group C, thus providing no evidence for a higher risk of infarction by Aprotinin treatment. When comparing the ASA group to non-ASA pre-treatment, a strong trend towards a reduction in MI rate becomes obvious, from 15% to 5% in favour of the ASA pre-treatment (P = 0.08). Concerning other peri-operative complications, no statistical difference between the groups could be detected.
                A reduction in post-operative blood loss in primary elective CABG surgery with intra-operative Aprotinin treatment could be confirmed. A low-dose ASA treatment combined with a high-dose aprotinin administration during surgery not only neutralized a potentially higher risk of bleeding, but did in fact reduce the post-operative blood loss. The protective effect of ASA on peri-operative MI has been evident through a reduction of MI rate in ASA treated patients. Desmopressin (DDAVP, 0.3 microgram/kg) has been used routinely after cardiopulmonary bypass, particularly in patients having antiplatelet therapy. Recently epsilon-aminocaproic acid (single dose of 5 g) given before cardiopulmonary bypass has been added to the protocol. One hundred consecutive patients taking desmopressin and epsilon-aminocaproic acid (group A) and another 100 taking desmopressin alone (group B) were analyzed. There was no difference among these two groups in patient age, sex, preoperative history of bleeding and drug consumption, or number of patients for elective, urgent, emergent, redo, and reoperation for bleeding. Results of routine preoperative coagulation studies were within normal limits in both groups. Preoperative hemoglobin level was 13.5 g/dL in group A and 13.8 g/dL in group B (p = 0.12). Estimated blood loss in the operating room was 513 mL for group A and 587 mL for group B (p = 0.07). The total chest drainage at the end of 24 hours was 492 mL in group A and 746 mL in group B (p = 0.0001). Amicar given before cardiopulmonary bypass does not lessen operating room blood loss, but significantly decreases postoperative chest drainage. Group B patients received more fresh frozen plasma (60 U versus 4 U), more platelets (130 U versus 16 U), and more cryoprecipitate (118 U versus 10 U) than group A patients. Adding epsilon-aminocaproic acid could save $206.18 in blood product use per patient, compared with the expense of $24.12 per patient for E-aminocaproic acid administration. The transfusion of allogeneic red blood cells and allogeneic coagulation products is associated with risk to the patient and the depletion of an increasingly scarce resource. This prospective, randomized, double-blind, placebo-controlled trial investigated practices to avoid transfusion in patients undergoing first-time cardiac surgery.
                Patients were randomized to one of three treatment groups: an aprotinin group, a tranexamic acid group, and a control group receiving normal saline. Intra-operative cell salvage was used for all patients. The primary outcomes were the number of patients exposed to allogeneic red blood cells, allogeneic coagulation products or any allogeneic transfusion (allogeneic red blood cells and/or allogeneic coagulation products).
                Patients were 2.5 times more likely to receive any allogeneic transfusion in the tranexamic group than in the aprotinin group (21 patients out of 60 compared with nine out of 60, respectively). The relative risk of any allogeneic transfusion comparing aprotinin with tranexamic acid was 0.43 (95% confidence interval 0.21-0.86; P=0.019). Patients in the control group were four times more likely to receive any allogeneic transfusion when compared with the aprotinin group (37 patients out of 60 compared with nine out of 60, respectively). The relative risk of any allogeneic transfusion comparing aprotinin with control was 0.24 (95% confidence interval 0.13-0.46; P<0.001).
                When used in addition to intra-operative cell salvage, aprotinin is the most efficacious pharmacological therapy for reducing patient exposure to any allogeneic transfusion during first-time cardiac surgery. Aprotinin reduces blood loss after cardiopulmonary bypass, but may sensitize recipients and is expensive. Tranexamic acid, a synthetic antifibrinolytic, has less disadvantages, but opinions differ regarding its efficacy. We studied three groups of patients undergoing cardiopulmonary bypass for coronary disease: recipients of aprotinin (total dose 4.2 x 10(6) kallikrein inhibiting units, n = 14), recipients of tranexamic acid (total dose 20 mg/kg body weight, n = 15), and nonmedicated controls (n = 14) during 24 hours after cardiopulmonary bypass. Compared with controls, aprotinin reduced blood loss, the number of patients requiring transfusions, and the mean number of transfused red cell units (all with p < 0.05), whereas the recipients of tranexamic acid did not differ either from aprotinin recipients or from controls. Aprotinin and tranexamic acid both mitigated the early postoperative reduction of adenosine diphosphate-induced platelet aggregation seen in the controls (p < 0.05). Postoperative increases of plasma concentrations of the prothrombin activation fragment F1 + 2 and the thrombin-antithrombin III complex showed an activation of intravascular coagulation, without any intergroup differences. The balance between concentrations of tissue plasminogen activator and the type 1 plasminogen activator inhibitor disclosed an activation of fibrinolysis, without differences between the groups. The concentrations of D-dimer, a breakdown product of cross-linked fibrin, remained at baseline in the recipients of aprotinin and tranexamic acid but tripled in the controls (p < 0.05). By contrast, the plasma antiplasmin activity was equally depressed in the tranexamic acid and the control groups but decreased less in the recipients of aprotinin (p < 0.05). This discrepancy may reflect the different modes of action of the two agents, which may make aprotinin more efficacious than tranexamic acid in the "nonfibrinolytic" act of protecting platelet function against attack by plasmin during cardiopulmonary bypass. Surgery for abdominal aneurysm is associated with substantial blood loss. In cardiac surgery, aprotinin, a fibrinolysis inhibitor, has shown to reduce blood loss significantly. Our aim was to assess the effect of aprotinin, when administered during elective surgery of infrarenal abdominal aneurysm, on coagulation, blood loss, and morbidity. A double-blind randomized trial was performed on 35 consecutive patients. They were randomized to either an aprotinin or a placebo group. The aprotinin group received 2,000,000 kallikrein inhibiting units (KIU) of aprotinin (500,000 KIU in 50 mL NaCl 0.9%) as a starting dose, followed by 500,000 KIU per hour during the operation. The placebo group received equal amounts of only NaCl 0.9%. During the operation and 24 hr thereafter, blood samples were taken to assess coagulation factors. Blood loss was measured in suction devices and swabs. All patients were followed until their discharge from the hospital. Statistical analysis was performed by independent t-test or Mann-Whitney U-test and chi-squared test. There was no significant difference in the amount of blood loss or the amount of blood products administered between the two groups. Morbidity and mortality were also comparable. In both groups, consumption of clotting factors could be detected, indicating activation of the coagulation cascade. However, in the aprotinin group, the alpha2-antiplasmin level was raised during surgery, indicating inhibition of fibrinolysis. Administration of aprotinin during elective operations for infrarenal aortic aneurysm induces inhibition of fibrinolysis. However, it does not significantly reduce blood loss or the need for blood products. In this prospective, placebo-controlled, double-blind, randomized clinical trial, we investigated the effect of a single preoperative bolus dose of tranexamic acid (15 mg/kg) on perioperative blood losses and packed cell transfusion requirements in patients scheduled for primary unilateral total hip replacement surgery for degenerative osteoarthrosis.
                40 patients were randomized to receive either 15 mg/kg tranexamic acid (TA group) or an equal volume of saline (placebo group) given as a single slow intravenous bolus injection 15 minutes before incision. We recorded per- and postoperative blood losses and transfusion requirements up to 24 hours postoperatively. The patients were screened for deep venous thrombosis with bilateral compression ultrasonography using colour Doppler imaging on the tenth postoperative day.
                Peroperative blood loss was not significantly different between the two treatment groups (TA group : 423 ml, placebo group 516 ml ; p = 0.093). Postoperative blood loss up to 24 hrs, and total blood loss were significantly less in the TA group : 352 vs 524 ml (p = 0.013), and 801 vs 1038 ml (p = 0.013), respectively. Packed red blood cell transfusion requirements were significantly lower in the TA group (1/20 patients, total 2 units) compared to the placebo group (6/20 patients, total 13 units). Compression ultrasonography on the 10th postoperative day was positive for deep venous thrombosis in 3 patients in the TA group (17 patients screened) and negative in all patients of the placebo group (18 patients screened).
                Tranexamic acid 15 mg/kg given as a single preoperative bolus dose reduces postoperative and total blood loss, and packed cell transfusion requirements in primary total hip replacement surgery. This prospective randomized study examined the effects of aprotinin during total hip arthroplasty (THA). Fifty patients who were enrolled in the study received aprotinin or normal saline. Mean intraoperative blood loss was reduced from 1496 mL in the control group to 1073 mL in the aprotinin group. The mean transfusion unit was 1.56 in the aprotinin group and 3.8 in the control group. A high-dose regimen of aprotinin 5-6 million KIU is effective in reducing bleeding and the need for homologous blood products (HBP) associated with cardiopulmonary bypass (CPB). These high doses aim at achieving plasmin and plasma kallikrein concentrations which in vitro are inhibitory but, theoretically, smaller doses could suffice in vivo. Also, aprotinin is an expensive drug, so efficiency requires using the smallest effective dose. Therefore, the efficacy of prophylactic aprotinin 1 million KIU (the maximal dose approved currently) was evaluated in a patient population at high risk of bleeding and of being transfused. Forty-one patients undergoing reoperation or a complex surgical procedure were included in a prospective, randomized, placebo-controlled, double-blind study. Before skin incision, a bolus of 200,000 KIU aprotinin was administered in 20 min, followed by an infusion of 100,000 KIU.hr-1 over eight hours. Control patients received an equal volume of saline. Dryness of the operative field, chest drainage, transfusion of HBP, haemoglobin concentrations, and coagulation variables (including bleeding time) were compared. There were no differences between aprotinin and placebo-treated patients for all clinical and laboratory variables. The apparent ineffectiveness of aprotinin may be explained by the use of an insufficient dose, by a different protocol of administration (e.g., no bolus in CPB prime), or by the inability of aprotinin to decrease bleeding and transfusions any further. Also, the number of patients studied does not exclude the possibility of a Type II error.(ABSTRACT TRUNCATED AT 250 WORDS) We performed a prospective, randomized, double-blind study on 40 patients scheduled for primary total hip arthroplasty due to arthrosis or osteonecrosis to determine the effect of tranexamic acid on per- and postoperative blood losses and on the number of blood transfusions needed.
                40 patients were randomized to tranexamic acid (10 mg/kg given as a bolus intravenous injection, followed by a continuous infusion of 1 mg/kg/hour for 10 hours) or placebo (20 mL saline given intravenously) 15 minutes before the incision. We recorded the peroperative and postoperative blood losses at removal of the drain 24 hours after the operation and the number of blood transfusions.
                Patients receiving tranexamic acid had a mean peroperative blood loss of 480 mL versus 622 mL in patients receiving placebo (p = 0.3), a postoperative blood loss of 334 mL versus 609 mL (p = 0.001), a total blood loss of 814 mL versus 1231 mL (p = 0.001) and a total need for 4 blood transfusions versus 25 (p = 0.04). No patient in either group had symptoms of deep venous thrombosis, pulmonary embolism or prolonged wound drainage.
                Transemic acid is effective in reducing the postoperative blood loss, the total blood loss and the need for blood transfusion in primary total hip arthroplasty. Cardiopulmonary bypass (CPB) increases risk of postoperative bleeding and need for transfusion. The aim of this study was to evaluate the effects of aprotinin, epsilon aminocaproic acid and tranexamic acid on coagulation patterns and need for banked blood transfusion. Ninety-six consecutive patients who underwent coronary artery bypass surgery were randomly assigned to 4 groups (24 patients each). The following parameters were monitored before, during and after CPB: activated lotting time, hemoglobin, prothrombin time, activated prothromboplastin time, fibrinogen, antithrombin III, xDP, Factor VIII, Thrombin-Antithrombin Complex and plasminogen. Analysis of postoperative bleeding and need for transfusion showed that the aprotinin group had significantly lower mediastinal bleeding. Transfused patients were 2, 4, 12 and 18 respectively in the aprotinin, epsilon aminocaproic acid, tranexamic acid and placebo treated group. In conclusion the use of protease inhibitors significantly reduces postoperative bleeding and transfusion. The aprotinin-treated group had the lower need for transfusion. Postoperative alterations in platelet function induced by cardiopulmonary bypass (CPB) are of importance. The effect on platelet aggregation of three different techniques for reducing blood consumption was studied in 30 patients undergoing elective aortocoronary bypass grafting from the beginning of anesthesia until the 1st postoperative day. The patients were randomly divided into three groups, in which 1) a cell separator was used during and after CPB; 2) a hemofiltration device was used; and 3) high-dose aprotinin was used in order to reduce the need of homologous blood. A fourth group undergoing neurosurgery procedures served as a control. Platelet aggregation induced by adenosine diphosphate (concentration 0.25, 0.50, 1.0, and 2.0 microM), collagen (4 microliters/ml), and epinephrine (25 microM) was determined by the turbidimetric method. Platelet aggregation was not significantly changed in the control group, indicating that the operation itself did not impair platelet function. At the end of the operation (after retransfusion of the salvaged pump blood), the maximum aggregation and maximum gradient of aggregation induced by all three inductors were most reduced (significantly) in the cell-separator patients. On the 1st postoperative day, platelet aggregation in the hemofiltration patients and the patients treated with aprotinin had normalized. Aggregation of patients pretreated with high-dose aprotinin was not different from that of the hemofiltration patients throughout the investigation. Blood loss was significantly highest in the cell-separator group (770 +/- 400 ml on the 1st postoperative day) but was not different between the hemofiltration (390 +/- 230 ml) and the aprotinin-treated patients (260 +/- 160 ml).(ABSTRACT TRUNCATED AT 250 WORDS) The aim was to determine whether the administration of aprotinin can cause deleterious effects on renal function in cardiac surgery with cardiopulmonary bypass (CPB).
                Sixty consecutive patients with normal preoperative renal function undergoing elective coronary artery bypass surgery with CPB using the same anaesthetic; CPB and surgical protocols were randomized into three groups. Patients received placebo (Group 1), low-dose aprotinin (Group 2) or high-dose aprotinin (Group 3). Renal parameters measured were plasma creatinine, alpha1-microglobulin and beta-glucosaminidase (beta-NAG) excretion. Measurements were performed before surgery, during CPB and 24 and 72 h, and 7 and 40 days postoperatively.
                In the three groups, alpha1-microglobulin and beta-NAG excretions significantly increased during CPB, at 24 and 72 h, and 7 days postoperatively (P < 0.05) and had returned to preoperative levels at postoperative day 40. Plasma creatinine levels were within normal values at times recorded. In Groups 2 and 3, alpha1-microglobulin excretion during CPB was significantly higher than in Group 1 (P < 0.001), and 24h after surgery it still remained significantly higher in Group 3 compared to Groups 1 and 2 (P < 0.05).
                Aprotinin caused a significant increase in alpha1-microglobulin excretion but not in beta-NAG excretion during CPB, which may be interpreted as a greater renal tubular overload without tubular damage. This effect persisted for 24 h after surgery when high-dose aprotinin doses had been administered. Creatinine plasma levels were not sensitive to detect these prolonged renal effects in our study. The serine protease antagonist, aprotinin, reduces perioperative blood loss in cardiac surgery and orthotopic liver transplantation. A pilot study suggested that the drug may also reduce bleeding during infrarenal aortic replacement; the aim was to confirm or refute this observation with a prospective, randomized, double-blind, placebo-controlled trial.
                Some 136 patients were randomized to receive either aprotinin, given as a loading dose of 2 x 10(6) kallikrein inactivator (KI) units followed by 0.5 x 10(6) KI units/h or equal volumes of 0.9 per cent saline. After 80 patients had been randomized the infusion dose was doubled to ensure that plasma levels were similar to those seen in successful cardiac studies. Blood loss, coagulation and haematological parameters were recorded throughout surgery and for 7 days afterwards. Blood was transfused to maintain the haemoglobin level at 100 g/l.
                Four patients were withdrawn after randomization when found at laparotomy to be unsuitable for the planned reconstruction. The 30-day mortality rate was 4.5 per cent, with no excess complications in either group. Blood loss collected on swabs was reduced from 480 ml in placebo-treated patients to 379 ml with aprotinin (P = 0.014). Blood loss into suction drains in the first 24 h after operation was reduced from 295 to 205 ml in aprotinin-treated patients (P = 0.002). However, no significant reduction was found in intraoperative or total blood loss, or transfusion requirement.
                The small reduction in blood loss in patients treated with aprotinin demonstrated in this study does not support its use in routine elective aortic surgery. Patients undergoing primary myocardial revascularization were randomized to one of three drug regimens (low-dose aprotinin, epsilon-aminocaproic Acid or tranexamic Acid) to determine which drug regimen would most effectively reduce post-operative bleeding and the need for blood products. All patients had received 325 mg of aspirin within 48 h before operation. All three drug regimens reduced the requirements for blood products and postoperative bleeding after coronary artery bypass operations. There was, however, no significant difference between drug regimens. This study examined whether differential effects of 2 agents commonly used for hemostatic purposes during cardiac surgery, aprotinin and epsilon-aminocaproic acid (EACA), exist with respect to elevations in proinflammatory interleukins (ILs) and matrix metalloproteinases (MMPs) in patients undergoing coronary artery bypass surgery. Sixty patients were prospectively randomized to receive either aprotinin (1 x 10 KIU; n = 30) or EACA (5 g IV; n = 30), and blood samples were obtained for IL and MMP levels just before induction of anesthesia (Baseline), 10 minutes after separation from cardiopulmonary bypass (Post), and 6 hours after surgery (6 hours). IL-6 was increased at Post in the EACA group and increased further at 6 hours. In the aprotinin group, IL-6 was significantly increased only at 6 hours. MMP subtypes associated with inflammation, MMP-8, and MMP-9 were increased in the EACA group at Post and remained elevated at 6 hours. Thus, differential effects on IL and MMP release occurred between aprotinin and EACA, indicative of different mechanisms of action independent of hemostatic effects. Nowadays in many European heart centers the activation of the fibrinolytic system, always occurring during cardiopulmonary bypass, is routinely reduced by high-dose application of the proteinase inhibitor aprotinin (total of > 4 million KIU). In this study parameters of myocardial ischemic injury were investigated with the aim of identifying further benefits of aprotinin, particularly the protection of the myocardium during the ischemic period of aortic crossclamping. Forty patients with coronary artery disease who underwent aorta-coronary bypass grafting were randomly and in a double-blind fashion divided into two groups, one that received high-dose aprotinin therapy and one that received only saline solution. Markers such as troponin T, with high specificity for detection of myocardial ischemia and infarction, and markers with more general specificity such as creatine kinase, its isoenzyme, and lactate dehydrogenase showed significantly increased values after ischemia in both groups. In patients who received high-dose aprotinin therapy 3 days after cardiopulmonary bypass all parameters measured showed significantly lower levels compared with those in the control group. Therefore we can presume that the application of high-dose aprotinin provides myocardial protection from perioperative ischemic injury. Extracorporeal circulation induces a systemic inflammatory response, which may adversely affect organ function. One manifestation of this response is increased fibrinolysis. Antifibrinolytic drugs such as aprotinin and epsilon-aminocaproic acid have been effective in reducing fibrinolysis and blood loss after extracorporeal circulation; however, the effects of antifibrinolytic drugs on proinflammatory and anti-inflammatory mediators are not known. This study examined the effects of aprotinin and epsilon-aminocaproic acid on plasma levels of proinflammatory [interleukin-6 (IL-6)] and anti-inflammatory [interleukin-10 (IL-10)] cytokines during and after extracorporeal circulation.
                Seventy-two patients undergoing coronary artery bypass grafting with extracorporeal circulation were randomly assigned in a double-blind study to receive high-dose aprotinin, epsilon-aminocaproic acid, or saline placebo. Plasma levels of IL-6 and IL-10 were measured at 5 time points before, during, and after extracorporeal circulation. In all 3 groups, both IL-6 and IL-10 rose significantly after institution of extracorporeal circulation and remained elevated through the first postoperative day. Compared with saline, aprotinin significantly reduced IL-10 (P=0.02) and peak IL-6 (P=0.02) after extracorporeal circulation. In contrast, none of the reductions in IL-6 and IL-10 by epsilon-aminocaproic acid achieved statistical significance. Both aprotinin and epsilon-aminocaproic acid decreased blood loss compared with saline, but there was no significant difference in the number of patients receiving blood products among the treatment groups.
                These data suggest that aprotinin and epsilon-aminocaproic acid differ in their effects on the inflammatory response to extracorporeal circulation. Aprotinin but not epsilon-aminocaproic acid appears to attenuate the rise in the proinflammatory and anti-inflammatory cytokines IL-6 and IL-10. Further studies will be required to determine if these cytokine alterations translate to changes in clinical outcomes. To determine the effect on aorta-coronary bypass grafts of high-dose aprotinin, a drug known to be effective in reducing bleeding after all forms of heart operations, a prospective double-blind study was performed. Graft patency was assessed noninvasively 7 to 12 days (median 9 days) postoperatively in 90 patients. In the aprotinin group, 38 of 43 patients had all grafts patent compared with 43 of 47 in the placebo group. In each group, respectively, 126 of 131 grafts versus 134 of 138 grafts were patent. Neither difference was statistically significant (p > 0.05). Blood loss and homologous blood use were significantly reduced in the aprotinin-treated patients. In this study, high-dose aprotinin did not result in early saphenous vein graft occlusion after aorta-coronary bypass operations. This is further evidence that aprotinin reduces hemostatic derangement during cardiopulmonary bypass without creating a "prothrombotic" situation. Numerous methods of controlling bleeding during total hip arthroplasty have been used. Thromboplastic agents have been used with some success, but the resultant fibrin layer interposed between the bone and cement weakens the interface. Topical freezing saline and hypotensive anesthesia have proved to be the most effective to date. The goal of this randomized, double blind, controlled study is to determine the effect of a single bolus dose of tranexamic acid, administered at the time of anesthesia, on bleeding during primary total hip arthroplasty. Fifty patients were randomized to receive either 10 mg/kg of tranexamic acid or a similar volume of normal saline as a preoperative bolus. Patients were not given pharmacologic thrombotic prophylaxis until 48 hours after surgery. The goal was to measure blood loss from the femoral canal at the time of surgery. An estimate of the internal and external blood loss during and after surgery was performed, and the transfusion requirement was recorded. No significant difference was found between the groups in terms of blood loss from the femoral canal, the perioperative bleeding, and postoperative hemoglobin. In the group that received tranexamic acid, a greater number of patients required transfusion than in the placebo group. The results of this study do not support the routine use of tranexamic acid in primary total hip arthroplasty. Cytokines are implicated in the pathogenesis of the "whole-body inflammatory response" that may complicate the period after cardiopulmonary bypass (CPB). Low-Dose aprotinin in the pump during CPB has been shown to improve postoperative hemostasis and platelet preservation. We tested the hypothesis that low-dose aprotinin influences the inflammatory reaction (in terms of cytokine release) after CPB.
                In a prospective, randomized study, 36 patients undergoing elective coronary artery bypass grafting were investigated. Nineteen patients received low-dose aprotinin (2 x 10(6) KIU (280 mg] in the pump), and a control group of 19 did not. Complement activation, cytokine production, leukocyte elastase release. D-dimer level, full blood count, postoperative blood loss, and transfusion requirements were analyzed before, during, and after after CPB.
                Interleukin-1 beta was not detected in either group, whereas traces of tumor necrosis factor-alpha were infrequently observed. Plasma elastase, interleukin-6, interleukin-8, and neutrophil count increased (p < 0.001) during and after CPB compared with the baseline levels, reaching a peak at 2 hours after protamine administration in both groups before returning toward baseline at 24 hours. Proinflammatory cytokine markers did not differ significantly (p > 0.1) between the groups throughout the study period. The C5b-9 level increased (p < 0.001) in both groups perioperatively, reaching its peak 15 minutes after protamine. Twenty-four-hour postoperative blood loss was significantly (p < 0.001) reduced in the aprotinin group in association with markedly reduced D-dimer levels (p < 0.001). Patients in the aprotinin group also received significantly less banked blood postoperatively than the control group (p < 0.01).
                Low-dose aprotinin fails to modify proinflammatory cytokine release, yet confers hemostatic improvement through reduced fibrinolysis in patients undergoing routine coronary artery bypass grafting. Until recently, aprotinin was the only antifibrinolytic drug with a licensed indication in cardiac surgery in the United States. The most popular alternative, epsilon-aminocaproic acid (EACA), has not been adequately compared with aprotinin. We undertook this study to test the hypothesis that EACA, when dosed appropriately, is not inferior to aprotinin at reducing fibrinolysis and blood loss.
                Seventy-eight patients scheduled for primary, isolated coronary artery bypass graft surgery were randomly assigned to receive "full Hammersmith" dose aprotinin, high dose EACA (100 mg/kg initial loading dose, 5 g in the pump prime solution, 30 mg x kg(-1) x h(-1) maintenance infusion) or equal volumes of a saline-placebo in a double-blind trial. Reductions in peak D-dimer formation (a measure of fibrinolysis) and 24-h chest tube drainage (CTD) were the primary end points by which noninferiority of EACA was tested. The noninferiority limit was set at a 30% increase in peak D-dimer formation (a difference of 250 microg/mL) and 24-h CTD (a difference of 350 mL) relative to aprotinin.
                The between-group differences (EACA versus aprotinin) in peak D-dimer formation (-3.58 microg/L, 95% CI -203 to 195 microg/L) and 24-h CTD (67 mL, 95% CI -90 to 230 mL) were within the predetermined noninferiority margins (250 microg/mL and 350 mL, respectively) and satisfied the criteria for noninferiority. Compared with saline, significant between-group reductions in peak D-dimer formation were observed using EACA (589 microg/L, 95% CI 399-788 microg/L; P < 0.0001) and aprotinin (585 microg/L, 95% CI 393-778 microg/L; P < 0.0001). Similar reductions in 24 h CTD were also seen using EACA (239 mL, 95% CI 50-415 mL; P < 0.05) and aprotinin (323 mL, 95% CI 105-485 mL; P < 0.05) compared with saline. Plasma EACA levels were maintained well above a target of 260 microg/mL.
                When dosed in a pharmacologically guided manner, EACA is not inferior to aprotinin in reducing fibrinolysis and blood loss in patients undergoing primary, isolated coronary artery bypass surgery. To determine if the use of an antifibrinolytic agent (epsilon aminocaproic acid [EACA]) decreased perioperative and postoperative blood loss in patients who underwent total hip arthroplasty (THA).
                A prospective, double-blind, randomized, controlled clinical trial.
                A university-affiliated tertiary care hospital with a large joint arthroplasty population.
                Fifty-five patients who were scheduled for a primary THA.
                Patients were randomly assigned to 2 groups to receive either EACA or saline placebo perioperatively. Preoperatively, the groups were similar with respect to gender, mean age, mean hemoglobin level, operative time and prosthesis type.
                Blood loss from the start of surgery until the Hemovac drain was removed, and the transfusion rate and hemoglobin levels.
                Mean (and standard error) total blood loss for patients receiving EACA was 867 (207) mL and for patients receiving placebo was 1198 (544) mL (p < 0.025). Four patients in the EACA group received 7 units of packed red blood cells and 7 patients in the saline group required 12 units.
                Patients receiving the placebo sustained greater total blood loss than EACA patients and were more likely to require blood transfusion. In the current climate of concern over blood transfusions during surgery, EACA administration can reduce blood loss and consequently transfusion and transfusion-related risk. A projected increase in total hip arthroplasties, shortfalls in blood availability, and awareness of complications of transfusion make blood management in orthopaedic surgery important. In a multicenter, randomized, double-blind, placebo-controlled study, we hypothesized use of aprotinin would reduce blood transfusions (any and allogeneic) and blood loss in total hip arthroplasty. Using an intent-to-treat approach, we recruited 393 patients stratified by preoperative autologous blood donation or none and then randomized them to receive aprotinin (176 patients receiving a 10,000 kallikrein inhibitor units [KIU] test dose, 2 million KIU load, 0.5 million KIU per hour) or placebo (177 patients). We assessed patients at baseline; postoperative days 1, 2, 3, and 7 (or discharge); and 6 +/- 2 weeks. Primary efficacy was percentage of patients having blood transfusion through day 7 or discharge. We based safety on reported adverse events. Aprotinin reduced transfusions by 46% (30 of 176 versus 56 of 177 patients). Aprotinin reduced the total number of any blood units and the number of allogeneic blood units transfused relative to placebo (48 versus 109 units and 30 versus 72 units, respectively). Serious complications were similar in the two groups (placebo, 11%; aprotinin, 10%). Our data suggest full-dose aprotinin is safe and effective in decreasing blood transfusion in total hip arthroplasty. Intraoperatively administered, tranexamic acid (TA) does not reduce bleeding in total hip replacement (THR). Therefore, its prophylactic use was attempted in the present study because this has been shown to be more effective in cardiac surgery. We investigated 40 patients undergoing THR in a prospective, randomized, double-blinded study. Twenty patients received TA given in two bolus doses of 10 mg/kg each, the first just before surgical incision and the second 3 h later. In addition, a continuous infusion of TA, 1.0 mg. kg(-1). h(-1) for 10 h, was given after the first bolus dose. The remaining 20 patients formed a control group. Both groups used preoperative autologous blood donation and intraoperative autotransfusion. Intraoperative bleeding was significantly less (P: = 0.001) in the TA group compared with the control group (630 +/- 220 mL vs 850 +/- 260 mL). Postoperative drainage bleeding was correspondingly less (P: = 0.001) (520 +/- 280 vs 920 +/- 410 mL). Up to 10 h postoperatively, plasma D-dimer concentration was halved in the TA group compared with the control group. One patient in each group had an ultrasound-verified late deep vein thrombosis. In conclusion, we found TA, administrated before surgical incision, to be efficient in reducing bleeding during THR. Implications: In a prospective, double-blinded study of 40 patients undergoing total hip replacement, the preoperative administration of tranexamic acid reduced bleeding by 35%, probably by decreasing induced fibrinolysis. Whether tranexamic acid therapy can replace predonation of autologous blood or intraoperative autotransfusion requires further study. In this study we compared the clinical efficiency, safety, and economic benefit of low-dose aprotinin with epsilon aminocaproic acid (EACA) in reducing bleeding after cardiopulmonary bypass operation.
                In a double-blind, randomized study, 100 patients received low-dose aprotinin (2 x 10(6) kallikrein inhibitor units) or EACA (20 g). The surgical procedure was single- or double-valve replacement with or without coronary artery bypass grafts.
                Mediastinal chest drainage and transfusion requirements with both therapies were similar. There were no urgent reoperations to secure hemostasis in either group. Similar levels of D-dimer with both therapies indicate a similar inhibition of fibrinolysis. Release of troponin I was less in the low-dose aprotinin group 1 and 4 hours after bypass, although electrocardiographic measurements did not reflect this difference. Levels of S-100beta and neuron-specific enolase were similar with both therapies, confirming that there was no difference in the occurrence of any adverse neurologic events in either group.
                Low-dose aprotinin and EACA showed similar effects on the reduction of intraoperative and postoperative bleeding. The lower cost of EACA with no change in safety outcome suggests it is the preferred treatment. Sixty consecutive patients undergoing elective open-heart surgery were prospectively enrolled in a study to compare the efficacy of 3 different antifibrinolytic drugs to reduce postoperative bleeding and to reduce homologous blood requirements in combination with blood-saving techniques and restrictive indications for blood transfusion. The patients were randomized to 1 of 4 intraoperative treatment regimens: 1) control (no antifibrinolytic therapy); 2) epsilon-aminocaproic acid (10 g IV at induction of anesthesia, followed by infusion of 2 g/h for 5 hours); 3) tranexamic acid (10 mg/kg IV within 30 minutes after induction of anesthesia, followed by infusion of 1 mg/kg per hour for 10 hours); or 4) high-dose aprotinin (2 million KIU IV at induction of anesthesia and 2 million KIU added to the extracorporeal circuit, followed by infusion of 500 thousand KIU/h during surgery). Hemoconcentration and reinfusion of blood drained from the operative field and the extracorporeal circuit after operation were used in all patients. Indications for blood transfusion were hypotension, tachycardia, or both, with hemoglobin values < 8.5 g/dL; or severe anemia with hemoglobin values < 7 g/dL. Compared with the blood loss in the control group, patients receiving aprotinin and epsilon-aminocaproic acid showed significantly less postoperative blood loss at 1 hour (control, 128 +/- 94 mL; aprotinin, 54 +/- 47 mL, p = 0.01; and epsilon-aminocaproic acid, 69 +/- 35 mL, p = 0.03); this trend continued at 24 hours after operation (control, 724 +/- 280 mL; aprotinin, 344 +/- 106 mL, p < 0.0001; and epsilon-aminocaproic acid, 509 +/- 148 mL, p = 0.01). Aprotinin was significantly more efficient than epsilon-aminocaproic acid (p=0.002). Tranexamic acid did not have a statistically significant effect on blood loss. Homologous blood requirements were not significantly different among the groups; postoperative hematologic values and coagulation times were also comparable. Despite the efficacy of aprotinin and epsilon-aminocaproic acid shown in the present study, the blood requirements were not significantly different from those that are found when transfusions are restricted, autotransfusions are used, and blood from the operative field and extracorporeal circuit is concentrated and reinfused. Therefore, intraoperative antifibrinolysis may not be indicated in routine cardiac surgery when other blood-saving techniques are adopted. nan In addition to blood-sparing effects, aprotinin may have cardioprotective and anti-inflammatory effects during cardiopulmonary bypass-assisted cardiac surgery. In this study, the authors examined whether aprotinin had cardioprotective and/or anti-inflammatory effects in patients undergoing off-pump coronary artery bypass grafting.
                A prospective randomized clinical trial.
                University hospital.
                Fifty patients were randomized to control (n = 25) or aprotinin treatment (n = 25) groups.
                Aprotinin was given as a loading dose (2 x 10(6) KIU) followed by a continuous infusion at 5 x 10(5) KIU/h until skin closure.
                Blood samples for cardiac troponin I; interleukin-6, interleukin-8, and interleukin-10; tumor necrosis factor alpha; and elastase were taken after anesthesia induction, completion of revascularization, and 6 hours, 12 hours, and 24 hours after revascularization. Blood samples were taken to assess for apoptosis in polymorphonuclear cells. Baseline plasma levels for cardiac troponin I did not differ between groups but were significantly lower in aprotinin-treated patients at the time of revascularization (p = 0.03) and 6 hours (p = 0.004) and 24 hours (p = 0.03) later. Aprotinin significantly reduced apoptosis in polymorphonuclear cells compared with control-treated patients (p = 0.04). There were no differences in plasma cytokine or elastase levels between groups.
                The authors conclude that aprotinin reduces perioperative cardiac troponin I release and attenuates apoptosis in polymorphonuclear cells but has no significant effects on plasma cytokine levels in patients undergoing off-pump coronary artery bypass graft surgery. Tranexamic acid has been suggested to be as effective as aprotinin in reducing blood loss and transfusion requirements after cardiac surgery. Previous studies directly comparing both antifibrinolytics focus on high-risk cardiac surgery patients only or suffer from methodological problems. We wanted to compare the effectiveness of tranexamic acid versus aprotinin in reducing postoperative blood loss and transfusion requirements in the patient group representing the majority of cardiac surgery patients: low- and intermediate-risk patients.
                We conducted a non-sponsored, double-blind, randomised, placebo-controlled trial in which 298 patients scheduled for low- or intermediate-risk (mean logistic EuroSCORE 4.1) first-time heart surgery with use of cardiopulmonary bypass were randomised to receive either tranexamic acid, high-dose aprotinin, or placebo. All patients had preoperative normal renal function. End points of the study were monitored from the time of surgery until patient discharge. This trial was executed between June 2004 and October 2006.
                Both antifibrinolytics significantly reduced blood loss and transfusion requirements when compared with placebo. Aprotinin was about twice as effective as tranexamic acid in reducing total postoperative blood loss (estimated median difference 155 ml, 95% confidence interval (CI) 60-260; p < 0.001). Accordingly, aprotinin reduced packed red blood cell transfusions more than tranexamic acid, although the difference did not reach statistical significance. Only aprotinin significantly reduced the proportion of transfused patients when compared with placebo (mean difference -20.9%, 95% CI 7.3-33.5; p = 0.013), and only aprotinin completely abolished bleeding-related re-explorations (mean difference 6.8%, 95% CI 1.6-13.4%; p = 0.004). Neither antifibrinolytic agent increased the incidence of mortality (mean difference tranexamic acid -0.4%, 95% CI -4.6 to 4.4; p = 0.79, mean difference aprotinin -1.3%, 95% CI -6.2 to 3.5; p = 0.62) or other serious adverse events when compared with placebo.
                Aprotinin has clinically significant advantages over tranexamic acid in patients with normal renal function scheduled for low- or intermediate-risk cardiac surgery. The recommended dose of aprotinin has been shown to reduce blood loss and need for blood transfusions, but the cost precludes its routine use. This study was designed to determine whether a less expensive, ultra-low dose of aprotinin is effective when used in coronary artery bypass grafting with left internal mammary artery.
                Patients (n = 202) were randomized to receive either placebo or aprotinin, 0.5 million KIU before incision and 0.5 million KIU during initiation of cardiopulmonary bypass. Differences in quantity of blood transfused were analyzed. Further groups were analyzed to account for the effect of aspirin. Multivariable analysis was performed to determine risk factors for transfusion. Direct costs of blood products and aprotinin were tabulated for each group.
                There was an important reduction in the proportion of patients transfused, and number of blood units transfused when aprotinin was given before coronary artery bypass grafting. These differences were even more important in patients on aspirin preoperatively. Independent predictors for increased number of transfusions were aspirin continued before operation, smaller body surface area, and the use of placebo instead of ultra-low dose aprotinin. There was no difference in morbidity between treatment groups. There was a reduction in direct costs associated with the use of aprotinin.
                These data support the routine use of aprotinin 1 million KIU in coronary artery bypass grafting with left internal mammary artery to reduce cost and transfusion requirements. Microvascular bleeding after Cardiopulmonary bypass (CPB) is mainly due to consumption of clotting factors, platelets damage, and hyperfibrinolysis. Aprotinin, the only antifibrinolytic drug effective in preserving platelets, is no longer available; an alternative regimen based on pure antifibrinolytic drugs has been proposed, since hyperfibrinolysis is known to contribute both to clot lysis and platelet dysfunction. In this study the efficacy of two antifibrinolytic drugs, Tranexamic acid (TA) and epsilon-aminocaproic acid (EACA), was tested in patients undergoing cardiopulmonary bypass (CPB), for primary myocardial revascularization.
                Forty-eight consecutive patients were randomized to receive prophylactically equipotent doses of EACA (group A) or TA (Group B). Platelet count, prothrombin time, fibrin digestion products, blood loss and transfusion requirements recorded after 6 and 24 hours from the end of surgery were compared.
                The two groups were comparable for length of CPB and numbers of grafts; no significant difference was observed in the coagulation parameters considered. Blood losses were less in group B (TA) than in group A (EACA), both at 6 and 24 hours after surgery; homologous blood transfused was also less in group B, but no difference was statistically significant. No adverse effect was observed.
                In coronary patients, TA and EACA exhibit the same effects on blood loss and requirements after CPB; either drug can be safely used in cardiac surgery. To study the efficacy of aprotinin in reducing whole blood loss after cardiac surgery with extracorporeal circulation.
                Two groups of patients undergoing cardiac surgery with extracorporeal circulation were studied. Group I (n = 51) received 2 x 10(6) KIU (kallikrein inhibiting units) of aprotinin upon anesthetic induction, a similar dose in the extracorporeal circulation priming pump, and a maintenance dose of 500,000 KIU/h until removal from the operating theater. Group II (n = 51) was the control group. Patients that had previously undergone surgery with extracorporeal circulation were excluded, as were those being treated with anti-coagulants or anti-aggregants. Data recorded were blood volume, transfusions needed in the first 24 h, and blood derivatives used throughout the hospital stay. Postoperative kidney function was also determined. The occurrence of acute myocardial infarction in patients undergoing myocardial revascularization was also noted.
                Group I required a mean of 2.40 U of concentrated red blood per patient during the first postoperative day, as opposed to a mean of 4.3 U in group II (p < 0.001). Blood loss through drains was also less in group I than in group II (431.82 vs 895.29 ml; p < 0.001). Total blood needed during the hospital stay was 3.50 units per patient in group I vs 5.40 U in group II (p < 0.001). Urea and creatinine were similar in the two groups before and after surgery (p = NS), and there were no significant differences in the number of cases of acute myocardial infarction in the two groups (3 in group I and 2 in group II).
                Administration of high doses of aprotinin is an effective technique for reducing the need for whole blood in patients requiring extracorporeal circulation during surgery. The technique does not compromise kidney function or increase the risk of perioperative acute myocardial infarction. Epsilon-aminocaproic acid is a plasmin inhibitor that potentially reduces perioperative bleeding when administered prophylactically to cardiac surgery patients. To evaluate the efficacy of epsilon-aminocaproic acid, a prospective placebo-controlled trial was conducted in patients undergoing primary coronary artery bypass grafting surgery.
                One hundred patients were randomly assigned to receive either epsilon-aminocaproic acid (100 mg/kg before skin incision followed by 1 g/hour continuous infusion until chest closure, 10 g in cardiopulmonary bypass circuit) or placebo, and the efficacy of epsilon-aminocaproic acid was evaluated by the reduction in postoperative thoracic-drainage volume and in donor-blood transfusion up to postoperative day 12.
                Postoperative thoracic-drainage volume was significantly lower in the epsilon-aminocaproic acid group compared with the placebo group (epsilon-aminocaproic acid, 649 +/- 261 mL; versus placebo, 940 +/- 626 mL; p=0.003). There were no significant differences between the epsilon-aminocaproic acid and placebo groups in the percentage of patients requiring donor red blood cell transfusions (epsilon-aminocaproic acid, 24%; versus placebo, 18%; p=0.62) or in the number of units of donor red blood cells transfused (epsilon-aminocaproic acid, 2.2 +/- 0.8 U; versus placebo, 1.9 +/- 0.8 U; p=0.29). Epsilon-aminocaproic acid did not reduce the risk of donor red blood cell transfusions compared with placebo (odds ratio: 1.2, 95% confidence interval; 0.4 to 3.2, p=0.63).
                Prophylactic administration of epsilon-aminocaproic acid reduces postoperative thoracic-drainage volume by 30%, but it may not be potent enough to reduce the requirement and the risk for donor blood transfusion in cardiac surgery patients. This information is useful for deciding on a therapy for hemostasis in cardiac surgery. We examined the effects of aprotinin on graft patency, prevalence of myocardial infarction, and blood loss in patients undergoing primary coronary surgery with cardiopulmonary bypass.
                Patients from 13 international sites were randomized to receive intraoperative aprotinin (n = 436) or placebo (n = 434). Graft angiography was obtained a mean of 10.8 days after the operation. Electrocardiograms, cardiac enzymes, and blood loss and replacement were evaluated.
                In 796 assessable patients, aprotinin reduced thoracic drainage volume by 43% (P < .0001) and requirement for red blood cell administration by 49% (P < .0001). Among 703 patients with assessable saphenous vein grafts, occlusions occurred in 15.4% of aprotinin-treated patients and 10.9% of patients receiving placebo (P = .03). After we had adjusted for risk factors associated with vein graft occlusion, the aprotinin versus placebo risk ratio decreased from 1.7 to 1.05 (90% confidence interval, 0.6 to 1.8). These factors included female gender, lack of prior aspirin therapy, small and poor distal vessel quality, and possibly use of aprotinin-treated blood as excised vein perfusate. At United States sites, patients had characteristics more favorable for graft patency, and occlusions occurred in 9.4% of the aprotinin group and 9.5% of the placebo group (P = .72). At Danish and Israeli sites, where patients had more adverse characteristics, occlusions occurred in 23.0% of aprotinin- and 12.4% of placebo-treated patients (P = .01). Aprotinin did not affect the occurrence of myocardial infarction (aprotinin: 2.9%; placebo: 3.8%) or mortality (aprotinin: 1.4%; placebo: 1.6%).
                In this study, the probability of early vein graft occlusion was increased by aprotinin, but this outcome was promoted by multiple risk factors for graft occlusion. Aprotinin has been reported to reduce bleeding in cardiac surgery patients. Its mechanisms of action on coagulation have not been fully elucidated. In a prospectively randomized study of 40 patients undergoing elective aortocoronary bypass grafting, the influence of high-dose aprotinin (2 million IU of aprotinin before CPB, 500,000 IU/h until the end of operation, 2 million IU added to the prime) (N = 20) on endothelial-related coagulation was compared to a nontreated control group (N = 20). Thrombomodulin (TM), protein C and (free) protein S as well as thrombin/antithrombin-III (TAT) plasma concentrations were measured by enzyme-linked immunosorbent assays (ELISA) before the aprotinin infusion, before cardiopulmonary bypass (CPB), during CPB and after CPB, at the end of surgery, 5 hours after CPB, and on the first postoperative day. All standard coagulation parameters (AT-III and fibrinogen plasma levels, platelet count, partial thromboplastin time) did not differ between the two groups. At baseline, TM plasma levels were within the normal range (< 40 ng/mL) and similar in both groups. During CPB, TM plasma concentrations decreased similarly in both groups (aprotinin: 18 +/- 6 ng/mL, control: 17 +/- 7 ng/mL) followed by a comparable increase in the postbypass period until the first postoperative day (aprotinin: 60 +/- 10 ng/mL, control: 53 +/- 11 ng/mL). Protein C and (free) protein S plasma levels also showed no differences between the two groups. On the first postoperative day, baseline values for protein C and protein S had not yet been reached.(ABSTRACT TRUNCATED AT 250 WORDS) nan The antifibrinolytic efficacy of a high-dose regimen of epsilon-aminocaproic acid (epsilon-ACA) was compared with aprotinin in first-time coronary operations.
                In a prospective, double-blinded, randomized study, 20 patients received high-dose epsilon-ACA (10 g both as a loading and cardiopulmonary bypass priming dose, 2.5 g/h until 4 hours after protamine), and another 20 patients received aprotinin (2 x 10(6) KIU [280 mg] for loading and priming, 0.5 x 10(6) KIU/h [70 mg/h]). Ten untreated patients served as controls.
                Both agents reduced postoperative levels of thrombin/antithrombin III complexes, D-dimers, fibrin degradation products, free plasma hemoglobin (epsilon-ACA versus aprotinin, p = not significant; p < 0.05 versus controls), and amount of retransfused autologous blood (p < 0.001). Epsilon-ACA increased, aprotinin suppressed antiplasmin-plasmin complex generation (epsilon-ACA versus controls, p < 0.02; epsilon-ACA versus AP, p < 0.0001). For 4 hours after discontinuation, more chest drainage occurred with epsilon-ACA than aprotinin (137 +/- 90 mL versus 62 +/- 29 mL; means +/- standard deviation; p < 0.02). Cumulative 12-hour drainage was similar for aprotinin (391 +/- 220 mL) and epsilon-ACA (582 +/- 274 mL), but higher without inhibitor (1,091 +/- 541 mL; p < 0.001 versus drugs). Postoperatively, aprotinin was associated with the lowest autologous retransfusion incidence and highest hematocrits (p < 0.01 versus epsilon-ACA). Homologous transfusion exposures did not differ.
                In first-time coronary operations, higher postoperative hematocrit and less shed blood retransfusion constitute only subtle advantages of aprotinin over high-dose epsilon-ACA. Aprotinin reduces blood loss in operations done with cardiopulmonary bypass, whereas the use of desmopressin remains controversial. We compared aprotinin, desmopressin, and placebo in a double-blind, randomized trial to evaluate bleeding and transfusion requirements.
                One hundred forty-nine patients (48 received aprotinin, 50 desmopressin, 51 placebo) were included. Blood loss and transfusion requirements were recorded and levels of Factor VIII coagulant activity, von Willebrand's factor, thrombin-antithrombin complexes, and D-dimer were measured. Overall blood loss was 195 +/- 146 ml/m2 in the aprotinin group, 400 +/- 192 ml/m2 in the desmopressin group, and 489 +/- 361 ml/m2 in the placebo group (95% confidence intervals: difference between desmopressin and aprotinin 98 to 312 ml/m2, p < 0.001; difference between placebo and aprotinin 190 to 398 ml/m2, p < 0.001). Twenty-six percent of patients treated with aprotinin, 66% of those treated with desmopressin, and 56% of those treated with placebo were given transfusion (95% confidence intervals: difference between aprotinin versus placebo plus desmopressin 51% to 71%, p < 0.001). Fibrinolytic activation throughout cardiopulmonary bypass was markedly higher with placebo or desmopressin administration. D-dimer level correlated with overall blood loss in patients receiving desmopressin or placebo, but not in those receiving aprotinin.
                Aprotinin administration reduces blood loss and transfusion requirements in cardiopulmonary bypass. This benefit may be explained by a lower activation of fibrinolysis. To assess the blood-sparing efficacy of tranexamic acid (TA) administered orally or via a variable IV infusion, 80 healthy patients undergoing elective total knee replacement were studied according to a prospective, controlled, randomized, single-blinded study design. Patients were allocated to one of four treatment groups. In group TA-long, 30 min before deflation of the limb tourniquet, an IV bolus dose of TA 15 mg/kg was administered over 30 min. Thereafter, a constant IV infusion of 10 mg . kg(-1) . h(-1) was administered until 12 h after final deflation of the limb tourniquet. In group TA-short, a similar regimen was followed; however, the constant IV infusion was discontinued 2 h after final deflation of the limb tourniquet (time of discharge from the postanesthesia care unit). Thereafter, oral TA 1 g was administered after 6 and 12 h. In group TA-oral, 60 min before surgery an oral dose of TA 1 g was administered. After surgery, a similar dose of TA was administered every 6 h for the next 18 h. In the control group, TA was not administered. At patient discharge, postoperative allogeneic blood administration was significantly more in group Control when compared with each of the three TA treatment groups. Because oral drug administration is simple and does not require specific infusion equipment, the authors suggest that oral TA is a superior blood-sparing strategy compared with IV drug administration. Two groups of patients were prospectively studied to evaluate the hemostatic effects of high-dose aprotinin in open heart operations. Group A patients (n = 22) received aprotinin during the entire surgical procedure. Group B patients (n = 12) served as controls. The groups were homogeneous for base variables and for cardiopulmonary bypass duration. Postoperative bleeding was lower in group A (mean, 486 mL) than in group B (830 mL) (p less than 0.01). The need for banked blood decreased by approximately half in the aprotinin patients (mean: group A, 213 mL; group B, 409 mL). Hemoglobin levels were similar in the two groups (postoperative day 7: group A, 11.29 g/100 mL; group B, 11.26 g/100 mL; NS). Platelet count decreased at the end of operation in both groups (99,000 and 95,000/mL, respectively; NS) and then increased beyond baseline levels before discharge. No complications were observed that could be attributed to aprotinin. In conclusion, we believe that the use of high-dose aprotinin is safe and effective. It decreases blood loss and reduces the need for banked blood in cardiac operations, particularly in select groups of patients (eg, those undergoing reoperation, Jehovah's Witnesses, those with renal failure). The effect of aprotinin (2,000,000 IU as a bolus +500,000 JU/h until the end of the operation) on transfusion requirements and coagulation parameters in orthotopic liver transplantation (study group: n = 9; placebo group: n = 9) was investigated in a randomised, double-blind study. Coagulation parameters were monitored intraoperatively using a mobile laboratory. In contrast to the published results, no effect on transfusion requirements could be demonstrated. However, aprotinin showed a positive effect on some coagulation parameters in the reperfusion phase. The mechanism appeared to be inhibition of the contact activation of the intrinsic system with less thrombin generation in the study group. This study was designed to evaluate the hemostatic effect of tranexamic acid in off-pump coronary artery bypass surgery.
                A prospective, randomized, double-blind, placebo-controlled study.
                The Department of Anesthesiology and Cardiac Surgery, Medical Sciences University.
                One hundred eight patients undergoing off-pump coronary artery bypass surgery were enrolled into the study. Eight patients were withdrawn, and 100 patients were divided into 2 groups.
                Fifty patients received tranexamic acid (bolus 1 g before skin incision and followed by maintenance dose of 400 mg/h during surgery), and 50 patients received saline.
                Hematologic parameters, volume of blood loss, blood transfusion, and other clinical data were recorded throughout the perioperative period. Twenty-four-hour postoperative blood loss was significantly less in the tranexamic acid group compared with the control group (471 +/- 182 v 844 +/- 303). Patients in the tranexamic acid group received significantly less allogeneic blood (8 v 31 units).
                Bleeding and hemorrhagic complications and the consequent need for allogeneic transfusion are still major problems after off-pump coronary artery bypass surgery. Tranexamic acid appears to be effective in reducing postoperative bleeding and the need for allogeneic blood products. Antifibrinolytic drugs including aprotinin and tranexamic acid are currently used in cardiac surgery to reduce postoperative bleeding and transfusion requirements, and may have different effects on platelets. We therefore evaluated platelet function after cardiopulmonary bypass (CPB) and cardiac surgery to determine the effect of either aprotinin or tranexamic acid.
                In a prospective, randomized study, 50 patients scheduled for elective cardiac surgery with CPB were evaluated. Patients received high-dose aprotinin (n = 25) or tranexamic acid (n = 25) as antifibrinolytic drugs. Coagulation and platelet function were assessed preoperatively, after CPB, 3 and 24 h after surgery using modified thrombelastography and whole blood aggregometry.
                Impaired coagulation after CPB occurred in both groups compared with preoperative data (P < 0.01). In contrast to modified thrombelastography, thrombin receptor-mediated aggregometry after CPB was significantly decreased only in those patients receiving tranexamic acid until the end of the study period in comparison to the aprotinin group (P < 0.05). Aprotinin-treated patients showed significantly less chest tube drainage (575 mL +/- 228 vs 1033 mL +/- 647, P < 0.05) and need for postoperative transfusion requirements (P < 0.01) compared with the tranexamic acid group.
                Platelet function measured by whole blood aggregometry is better preserved by aprotinin than tranexamic acid and may be responsible for producing less bleeding within the first 24 h after CPB. We investigated consecutive patients undergoing primary total hip replacement surgery who were randomly assigned into two groups; those who received a blinded solution of aprotinin 2 million KIU (kallikrein inactivation units) (n = 11) and those who received an equivalent volume of normal saline placebo (n = 10) throughout the surgical procedure. Anesthesia and surgical techniques were standardized. All patients received spinal anesthesia combined with general anesthesia. There was no significant difference in blood loss during operation between the two groups. However, postoperative blood loss in the aprotinin group (284 +/- 155g, mean +/- SD) was significantly less compared with that in the control group (723 +/- 334g). Total blood loss in the aprotinin group (820 +/- 255g) was also significantly less than in control group (1265 +/- 389g). We conclude that the use of aprotinin 2 million KIU during total hip replacement results in significantly less perioperative blood loss, especially during the postoperative period. Patients undergoing cardiac surgery with moderate hypothermic cardiopulmonary bypass (CPB) were allocated randomly to receive either saline (control group, n = 29) or a high-dose regimen of aprotinin (aprotinin group, n = 28). In both groups, CPB was associated with similar and transient increases in effective renal plasma flow (+54% in controls and +48% in aprotinin-treated patients) and in fractional excretion of sodium and potassium, but glomerular filtration rate remained unchanged. Plasma and urinary ratios of 6-keto-PGF1 alpha to thromboxane B2 (TxB2) increased significantly, indicating systemic and renal release of vasodilatory prostaglandins. Osmolar clearance correlated with urinary excretion of cyclic GMP (r = 0.79 and 0.86 in the control and aprotinin groups, respectively) and 6-keto-PGF1 alpha (r = 0.63 and 0.69 in the control and aprotinin groups, respectively). Compared with preoperative values, plasma atrial natriuretic peptide increased after weaning from CPB (+71% and +93% in the control and aprotinin groups, respectively). Aprotinin had no apparent adverse effect on renal function and it did not alter mechanisms involving prostanoids and atrial natriuretic peptide during cardiac surgery. The perioperative blood coagulation and fibrinolysis system in patients who underwent aortic surgery under deep hypothermic circulatory arrest with or without aprotinin usage was investigated.
                Of 112 patients who underwent aortic surgery between December 1993 and April 1995, 60 had repair under deep hypothermic circulatory arrest. Thirty-nine patients had 2 million U aprotinin in pump priming and had no additional aprotinin. There were 20 patients with aortic dissections and 17 with atherosclerotic aneurysms. Twenty-two patients had left thoracotomy, and 17 had midsternotomy. Surgery consisted of replacement of the ascending aorta in 9 patients, total arch replacement in 11, distal arch replacement in 11, replacement of the descending aorta in 3, and replacement of thoracoabdominal aorta in 5. The control group was 21 patients who underwent operation under deep hypothermic circulatory arrest and retrograde cerebral perfusion but without aprotinin. Blood coagulation and fibrinolysis tests, consisting of activated clotting time, prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, plasminogen, alpha 2-plasmin inhibitor, thrombin-antithrombin complex, plasmin inhibitor complex, fibrin degenerative products, and D-dimer complex, were performed at various stages of surgery, before heparin administration, after heparin, 60 minutes and 120 minutes after beginning of the extracorporeal circulation, 1 hour after protamine administration, and 6 hours after protamine. Statistical analysis was performed with Student's t test, chi 2 test, and ANOVA. The amount of bleeding after perfusion was less in the aprotinin group, and bleeding during first 24 hours in the intensive care unit was less. Blood examination revealed that prothrombin time was higher after cessation of cardiopulmonary bypass in the aprotinin group. Thrombin-antithrombin III complex and alpha 2-plasmin inhibitor were higher during and after bypass in the aprotinin group. There was no difference in activated clotting time, activated partial thromboplastin time, fibrinogen, antithrombin III, plasminogen, plasmin inhibitor complex, fibrin degenerative products, and D-dimer complex.
                Clinical advantages of hemostatic effects of low-dose aprotinin and no apparent deleterious effects were demonstrated in patients who underwent aortic surgery under deep hypothermic circulatory arrest with retrograde cerebral perfusion. However, blood coagulation and fibrinolytic studies revealed subclinical hypercoagulation. Therefore, and adequate dose of heparin is required during deep hypothermic circulatory arrest. Low-dose aprotinin inhibits hyperfibrinolysis in cardiac surgery. However, excessive postoperative bleeding and increased fibrinolysis may occur despite low dose-aprotinin administration. We investigated (i) whether fibrinolytic activity significantly rises under low-dose aprotinin administration, and (ii) whether this is associated with excessive postoperative bleeding (> or = 1000 ml/24 h). In a prospective single-blind trial, 120 consecutive patients were randomized to receive 280 mg aprotinin or no aprotinin before skin incision. D-dimer levels increased significantly to the end of surgery, reaching higher levels in the control group. The risk for excessive bleeding was lower in the aprotinin group (12 versus 37%, = 0.001). Fifteen minutes after heparin reversal, patients were at risk for excessive bleeding, when enhanced fibrinolysis was documented (aprotinin group, D-dimer > or = 1.0 micro g/ml, odds ratio = 9.1, = 0.047; control group, D-dimer > or = 3.0 micro g/ml, odds ratio = 4.6, = 0.014). Ninety-seven per cent of the aprotinin group and 81% of control group patients had no excessive bleeding when the D-dimer plasma level was below these values. We conclude that (i) fibrinolytic activity significantly rises under low-dose aprotinin administration, and (ii) plasma D-dimer levels at end of surgery may help to identify patients who are unlikely to develop excessive postoperative bleeding. Total arterial grafting is increasingly preferred in coronary artery bypass grafting, but it increases blood loss. Aprotinin (Trasylol; Bayer Corp, Leverkusen, Germany) reduces blood loss in cardiac surgery but has not been subjected to a randomized trial in total arterial grafting.
                A single-center, randomized, double blind, placebo-controlled trial of aprotinin administration in total arterial grafting was performed. The primary outcome variable was postoperative blood loss, and the secondary outcome variable was the number of units of donor blood or coagulant products transfused. The incidence of myocardial injury was determined from serial measurements of cardiac troponin T and creatine kinase-MB and renal injury from serum creatinine.
                The placebo group (n = 34) and aprotinin group (n = 36) were similar with respect to all preoperative and intraoperative comparisons. One patient in each group underwent reexploration for bleeding. Open-label aprotinin was administered to 9 patients in the placebo group (26%) and to 2 patients in the aprotinin group (6%). There was a highly significant reduction in the median (interquartile range) blood loss in the aprotinin group compared with the placebo group (785 mL [590-1025 mL] vs 1525 mL [1175-1920 mL], respectively). Similarly, the aprotinin group demonstrated a marked reduction in the need for blood transfusion (77% vs 39%; P =.0001), the mean number of transfused blood units (2.6 vs 0.8, P <.001), and the number of patients requiring coagulant products (24% vs 3%; P <.001). There was no difference in myocardial injury in the 2 groups. Four patients in the aprotinin group had persistently elevated creatinine levels in the postoperative period (3 of whom had elevated preoperative creatinine levels and perioperative complications).
                Aprotinin significantly reduces blood loss and the need for blood component transfusion in patients undergoing total arterial grafting without increasing the risk of myocardial injury. Aprotinin should be considered routinely in patients undergoing total arterial grafting but cautiously in patients with an elevated preoperative creatinine level. We studied 99 patients who were undergoing total knee arthroplasty (TKA) to determine the optimum protocol for the administration of tranexamic acid (TNA) in order to reduce blood loss. It decreased by more than 40% after the administration of TNA. The haemostatic effect was greatest when TNA was given preoperatively and on deflation of the tourniquet. There was no increase in the incidence of adverse affects in the patients receiving TNA, compared with a control group. We conclude that two injections of TNA, one given preoperatively and one on deflation of the tourniquet, significantly reduce blood loss without increasing the risk of thromboembolic complications. Various dosages of aprotinin have proven to be effective in reducing blood loss and allogeneic transfusion requirements in cardiopulmonary bypass surgery, despite the controversy surrounding the precise hemostatic mechanisms of this drug. The aim of our prospective, randomized, double-blind study was to assess differences in blood loss and transfusion requirements and the effect of two dosages of aprotinin on hemostatic activation.
                Patients undergoing coronary artery bypass grafting received high-dose aprotinin (n=28), pump-prime-only (PPO) aprotinin (n=28), or placebo (n=28).
                The high-dose and the PPO groups had a significantly lower blood loss (985 mL [95%CI 845-1,102] and 1,255 mL, [95% CI 1,025-1,406], respectively) than the placebo group (1,416 mL, 95%CI 1,248-1,612]. Transfusion requirements were lower in the aprotinin-treated groups than in the patients receiving placebo (21 units and 15 units in the high and low-dose groups vs 59 units in placebo group). As far as concerns parameters of thrombin generation, the aprotinin groups showed a significant reduction of F1+2 prothrombin fragment but not of thrombin-antithrombin complexes. There were higher levels of natural anticoagulants, i.e. antithrombin, protein C and protein S, in the high-dose aprotinin group. As regards fibrinolysis parameters, D-dimer was lower in the aprotinin groups, and the levels of alpha2-antiplasmin and plasmin-alpha2-antiplasmin complexes were raised. In summary, both dosages of aprotinin were equally effective in reducing blood loss and transfusion requirements. There was a lower activation of coagulation and fibrinolysis in cardiopulmonary bypass patients treated with aprotinin: the levels of natural anticoagulants were less decreased in the high-dose group. No differences in thrombotic complications were observed between aprotinin groups.
                Our study shows that both dosages of aprotinin are safe and effective in reducing transfusion requirements. Considering the difference in cost of using a low-dose or high-dose schedule, the former should be recommended for patients undergoing cardiopulmonary bypass surgery. This study was designed to determine the benefit of aprotinin therapy in reducing bleeding during and after cardiopulmonary bypass in patients with preoperative platelet dysfunction. Platelet function involvement in the mechanism by which aprotinin acts was also investigated.
                In a double-blind, randomized study, patients received high-dose aprotinin (n = 54) or placebo (n = 52). Whole blood aggregation was measured preoperatively. Platelet function and activation in both groups were assessed intraoperatively and postoperatively at five times.
                Aprotinin significantly reduced perioperative bleeding and postoperative blood transfusion. Placebo-treated patients with reduced preoperative platelet aggregation bled more postoperatively, but aprotinin reduced the bleeding in patients with normal or reduced platelet function to similar levels. Any cardiopulmonary bypass-induced changes in platelet aggregation, platelet activation as measured by P-selectin expression, and von Willebrand factor antigen and function were similar in aprotinin-treated and placebo-treated groups.
                The mechanism by which aprotinin reduced bleeding was independent of any effect on platelet function. However, aprotinin produced a greater reduction in bleeding among patients whose condition was hemostatically compromised by preoperative platelet dysfunction. Despite recent rediscovery of beating heart cardiac surgical techniques, extracorporeal circulation remains appropriate for most heart operations. To minimize deleterious effects of cardiopulmonary bypass, antiinflammatory strategies have evolved.
                Four state-of-the-art strategies were studied in a prospective, randomized, preoperatively risk stratified, 400-patient study comprising primary (n = 358), reoperative (n = 42), coronary (n = 307), valve (n = 27), ascending aortic (n = 9), and combined operations (n = 23). Groups were as follows: standard, roller pump, membrane oxygenator, methylprednisolone (n = 112); aprotinin, standard plus aprotinin (n = 109); leukocyte depletion, standard plus a leukocyte filtration strategy (n = 112); and heparin-bonded circuitry, centrifugal pumping with surface modification (n = 67).
                Analysis of variance, linear and logistic regression, and Pearson correlation were applied. Actual mortality (2.3%) was less than half the risk stratification predicted mortality (5.7%). The treatment strategies effectively attenuated markers of the inflammatory response to extracorporeal circulation. Compared with the other groups the heparin-bonded circuit had highly significantly decreased complement activation (p = 0.00001), leukocyte filtration blunted postpump leukocytosis (p = 0.043), and the aprotinin group had less fibrinolysis (p = 0.011). Primary end points, length of stay, and hospital charges, were positively correlated with operation type, age, pump time, body surface area, stroke, pulmonary sequelae, predicted risk for stroke, predicted risk for mortality, and risk strata/treatment group interaction (p = 0.0001). In low-risk patients, leukocyte filtration reduced length of stay by 1 day (p = 0.02) and mean charges by $2,000 to $6,000 (p = 0.05). For high-risk patients, aprotinin reduced mean length of stay up to 10 fewer days (p = 0.02) and mean charges by $6,000 to $48,000 (p = 0.0007).
                These pharmacologic and mechanical strategies significantly attenuated the inflammatory response to extracorporeal circulation. This translated variably into improved patient outcomes. The increased cost of treatment was offset for selected strategies through the added value of significantly reduced risk. This prospective randomized double-blind trial evaluates the efficacy of tranexamic acid (TA) to decrease blood losses and red blood cell transfusions in patients undergoing primary unilateral total hip replacement (THR).
                Forty ASA class I to III patients received either iv TA 10 mg.kg(-1) bolus before surgery plus a 1 mg.kg(-1).hr(-1) infusion until wound closure (Group TA) or a placebo (Group P). Red blood cell transfusions were administered according to a standardized protocol.
                One patient of Group P was excluded because of an erroneous diagnosis at enrollment. Total measured blood losses (Group TA: 1308 +/- 462 mL vs Group P: 1469 +/- 405 mL), preoperative hemoglobin levels (Group TA: 130.4 +/- 12.5 g.L(-1) vs Group P: 131.4 +/- 12.8 vs g.L(-1)), and seven-day postoperative hemoglobin values (Group TA: 97.8 +/- 11.8 g.L(-1) vs Group P: 102.9 +/- 12.2 g.L(-1)) were similar. Autologous whole blood was available in five patients of Group P and seven patients of Group TA. Fewer patients in Group TA required red blood cells (Group TA: 6/20 vs Group P: 13/19; P = 0.026) and allogenic red blood cell transfusions (Group TA: 0/20 vs Group P: 8/19; P = 0.0012). The median number of transfused unit per patient was also significantly less in patients of Group TA (0 unit) than in Group P (2 units; P = 0.03).
                TA did not change measured blood losses but reduced red blood cell transfusion requirements in patients undergoing primary unilateral THR. To rule out the effect of high-dose aprotinin in respect to the balance of proinflammatory and anti-inflammatory mediators induced by cardiopulmonary bypass (CPB).
                Randomized, double-blind, placebo-controlled study.
                University-affiliated cardiac center.
                Twenty patients scheduled for coronary artery bypass graft surgery.
                In group A patients (n = 10), high-dose aprotinin was administered (2 x 106 KIU pre-CPB, 2 x 10(6) KIU in prime, 500,000 KIU/hr during CPB). In group C patients (n = 10), placebo was used instead. Proinflammatory interleukin (IL)-6, anti-inflammatory IL-1-receptor antagonist, and clinical parameters were measured 8 times perioperatively. The values are presented as mean +/- SEM.
                Four hours after CPB, IL-6 concentration reached the maximum value, being significantly lower in group A patients as compared with group C patients (615 +/- 62 pg/mL v 1,409 +/- 253 pg/mL; p = 0.019). On the first postoperative day, the concentration of IL-6 in group A patients remained lower (219 +/- 24 pg/mL v 526 +/- 123 pg/mL; p = 0.015). In contrast, IL-1-receptor antagonist concentration was higher in group A patients as compared with group C patients after CPB (13,857 +/- 4,264 pg/mL v 5,675 +/- 1,832 pg/mL; p = 0.03). Total postoperative blood loss was lower in group A patients as compared with group C patients (648 +/- 64 mL v 1,284 +/- 183 mL; p = 0.002).
                High-dose aprotinin treatment reduced the inflammatory reaction and postoperative blood loss. The anti-inflammatory reaction was significantly enhanced in these patients, which suggests that the physiologic reaction of the organism to reduce the deleterious effects from CPB is more pronounced by using high-dose aprotinin. Cognitive deficit after coronary artery bypass surgery (CABG) has a high prevalence and is persistent. Meta-analysis of clinical trials demonstrates a decreased incidence of stroke after CABG when aprotinin is administrated perioperatively. We hypothesized that aprotinin administration would decrease the incidence of cognitive deficit after CABG.
                Thirty-six ASA III-IV patients undergoing elective CABG were included in a prospective, randomized, single-blinded pilot study. Eighteen patients received aprotinin 2 x 10(6) KIU (loading dose), 2 x 10(6) KIU (added to circuit prime) and a continuous infusion of 5 x 10(5) KIU.hr(-1). A battery of cognitive tests was administered to patients and spouses (n = 18) the day before surgery, four days and six weeks postoperatively.
                Four days postoperatively new cognitive deficit (defined by a change in one or more cognitive domains using the Reliable Change Index method) was present in ten (58%) patients in the aprotinin group compared to 17 (94%) in the placebo group [95% confidence interval (CI) 0.10-0.62, P = 0.005); (P = 0.01)]. Six weeks postoperatively, four (23%) patients in the aprotinin group had cognitive deficit compared to ten (55%) in the placebo group (95% CI 0.80-0.16, P = 0.005); (P = 0.05).
                In this prospective pilot study, the incidence of cognitive deficit after CABG and cardiopulmonary bypass is decreased by the administration of high-dose aprotinin. To examine pump-prime aprotinin action on coagulation and fibrinolysis in patients undergoing primary coronary revascularization.
                A prospective randomized study.
                A university hospital.
                Forty-three patients were randomly assigned to either group A, 21 patients treated with 2 x 10(6) kallikrein inhibitor units (KIU) of aprotinin in the cardiopulmonary bypass (CPB) prime, or group B, 22 patients, untreated.
                Patients, scheduled for elective coronary surgery, were treated with 2 x 10(6) KIU of aprotinin in the CPB prime. Markers of coagulation and fibrinolysis were evaluated.
                Surgical times, number of reopenings, and allogeneic blood requirements were collected for each patient. Blood samples were obtained before and after surgery for assessing coagulation (prothrombin time [PT], activated partial thromboplastin time [aPTT], ethanol test, factor VII, antithrombin III [AT III], thrombin-antithrombin III complex [TAT], fragment 1.2 of prothrombin [F1.2]) and fibrinolysis (fibrin degradation products [FOP], plasmin-antiplasmin complexes [PAP], D-dimers) markers variations. In group A surgical times were faster, there were fewer reopenings (0 v 3), and fewer blood transfusions (1 patient v 4 patients). The two groups did not differ for PT, aPTT, and fibrinogen measurements. Postoperative FDP (measurable in more patients of group B at the end of the operation), PAP, and D-dimers postoperatory levels (less increased in aprotinin group) show the antifibrinolytic properties of the drug. Regarding the coagulation markers, factor VII decreased, whereas TAT and F1.2 increased, all to a lesser extent in the aprotinin group compared with the untreated patients, at the end of operation.
                Pump-prime aprotinin minimized, even if not completely inhibited, the activation of coagulation and fibrinolysis during CPB, possibly ensuring a less complicated and safer postoperative recovery. It seemed to allow the maintenance of a correct balance of hemostatic systems, avoiding the risk of thrombotic phenomena. Effects of aprotinin in off-pump coronary artery bypass (OPCAB) surgery have not yet been described. This study analyses hemostasiologic changes and potential benefit in OPCAB patients treated with aprotinin.
                In a prospective, double-blind, randomized study 47 patients undergoing OPCAB surgery were investigated. Patients received either aprotinin (2 x 10(6) KIU loading dose and 0.5 x 10(6) KIU/h during surgery, n=22) or saline solution (control, n=25). Activated clotting time was adjusted to a target of 250 s intraoperatively. Blood samples were taken up to 18h postoperatively: complete hematologic and hemostasiologic parameters including fibrinopeptide A (FPA) and D-dimer in a subgroup of 31 patients were analyzed. Blood loss, blood transfusion and other clinical data were collected.
                Both groups showed comparable demographic and intraoperative variables. Forty-one (87%) patients of the whole study group received aspirin within 7 days prior to surgery. Number of grafts per patient were comparable (2.9+/-1.0 [mean+/-SD] in the aprotinin group and 2.8+/-1.2 in control, P=0.83). Blood loss during the first 18 h in intensive care unit was significantly reduced in patients treated with aprotinin (median [25th-75th percentiles]: 500 [395-755] ml vs. 930 [800-1170] ml, P<0.001). Postoperatively only two patients (10%) in the aprotinin group received packed red blood cells, whereas eight (35%) in the control group (P=0.07). Perioperatively FPA levels reflecting thrombin generation were elevated in both groups. The increase in D-dimer levels after surgery was significantly inhibited in the aprotinin group (P<0.001). Early clinical outcome was similar in both groups.
                Aprotinin significantly reduces blood loss in patients undergoing OPCAB surgery. Inhibition of enhanced fibrinolysis can be observed. FPA generation during and after OPCAB surgery seems not to be influenced by aprotinin. In patients with coronary artery disease, continuation of aspirin may reduce the incidence of unstable angina and preoperative myocardial infarction before surgery, but the risk of perioperative bleeding may be increased.
                The efficacy of aprotinin and tranexamic acid (TXA) was examined in a prospective, randomized, double-blind trial involving 56 patients scheduled for coronary artery bypass grafting and who received aspirin 100 mg/day until the day of the operation. Group I received high-dose aprotinin whereas group II received 10 g of tranexamic acid (TXA) over 20 minutes before sternotomy. Heparinization during cardiopulmonary bypass was controlled with HDTT (high-dose thrombin time) to eliminate interference of aprotinin on ACT (celite activated clotting time). Postoperative blood loss and transfusion requirements were registered during the first 24 hours.
                The demographics, coagulation, and intraoperative parameters were similar in both groups. Postoperative blood loss (aprotinin 840 mL /24 hours, TXA 880 mL/24 hours, p = 0.481), and transfusion requirements (2.18 units/patient in the aprotinin group, 2.11 units/patient in the TXA group) were not remarkably different between the two regimen protocols. No perioperative myocardial infarction, pulmonary embolism, cerebrovascular event, or other thrombotic events were observed.
                In this trial, we were not able to demonstrate any difference in postoperative bleeding in patients pretreated with aspirin after high-dose aprotinin or TXA. From a practical point of view, TXA is safe, less expensive than aprotinin, and easy to handle, and can be recommended in patients pretreated with aspirin to improve postoperative hemostasis. Intraoperative hyperfibrinolysis contributes to bleeding during adult orthotopic liver transplantation. We aimed to find out whether aprotinin, a potent antifibrinolytic agent, reduces blood loss and transfusion requirements.
                We did a randomised, double-blind, placebo-controlled trial in which six liver-transplant centres participated. Patients undergoing primary liver transplantation were randomly assigned intraoperative high-dose aprotinin, regular-dose aprotinin, or placebo. Primary endpoints were intraoperative blood loss and transfusion requirements. Secondary endpoints were perioperative fluid requirements, postoperative blood transfusions, complications, and mortality.
                137 patients received high-dose aprotinin (n=46), regular-dose aprotinin (n=43), or placebo (n=48). Intraoperative blood loss was significantly lower in the aprotinin-treated patients, with a reduction of 60% in the high-dose group and 44% in the regular-dose group, compared with the placebo group (p=0.03). Total amount of red blood cell (homologous and autologous) transfusion requirements was 37% lower in the high-dose group and 20% lower in the regular-dose group, than in the placebo group (p=0.02). Thromboembolic events occurred in two patients in the high-dose group, none in the regular-dose group, and in two patients in the placebo group (p=0.39). Mortality at 30 days did not differ between the three groups (6.5%, 4.7%, and 8.3%; p=0.79).
                Intraoperative use of aprotinin in adult patients undergoing orthotopic liver transplantation significantly reduces blood-transfusion requirements and should be routinely used in patients without contraindications. Tranexamic acid has been found to reduce blood loss and the need for blood transfusions in knee arthroplasty. In hip arthroplasty, the benefit of tranexamic acid is not as clear.
                In a randomized, double-blind study, 39 patients with primary cemented hip arthroplasty for osteoarthritis were divided into two groups; one receiving tranexamic acid and the other not receiving it. Tranexamic acid was given in a dose of 10 mg/kg before the operation and twice thereafter, at 8-hour intervals.
                Total blood loss was smaller in the tranexamic acid group than in the control group. No thromboembolic complications were noticed. Tranexamic acid appears to be an effective and economic drug for reduction of blood loss in cemented primary hip arthroplasty for osteoarthritis. Perioperative use of tranexamic acid (TA), a synthetic antifibrinolytic drug, decreases perioperative blood loss, and the proportion of patients receiving blood transfusion in cardiac surgery, but the results may vary in different clinical settings. The primary objective of the present study was to determine the efficacy of TA to decrease chest tube drainage and the proportion of patients requiring perioperative allogeneic transfusions following primary, elective, on-pump coronary artery bypass grafting (CABG) in patients with a low baseline risk of postoperative bleeding.
                In a double-blinded, prospective, placebo-controlled study, 46 patients were randomized into two groups. One group received TA 1.5 g as a bolus, followed by a constant infusion of 200 mg/h until 1.5 g. The other group received placebo (0.9% saline). Among exclusion criteria were treatment with acetylsalicylic acid, non-steroidal anti-inflammatory drugs or other platelet inhibitors within 7 days before surgery.
                Preoperative demographics, biochemical and surgical characteristics were comparable between groups. At 6 h postoperatively, there was a trend towards a greater blood loss (median and interquartile range) in the placebo group (710 and 460-950 ml) compared to the TA group (400 and 350-550 ml), but the difference did not reach statistical significance. Neither were transfusion rates and the amount of autotransfused shed mediastinal blood different between the groups postoperatively. Postoperative d-dimer concentrations were significantly higher in the placebo group compared to the TA group (P < 0.001) This difference could not be explained by differences in the amount of autotransfused shed mediastinal blood alone. Plasma concentrations of beta-thromboglobulin and platelet factor 4 were significantly increased postoperatively in both groups, but without any intergroup differences. Seven patients (15%), one in the TA group and six in the placebo group, were reoperated due to excessive bleeding. Surgical correctable bleeding was found in all except two patients from the placebo group.
                An antifibrinolytic effect following prophylactic use of TA in elective, primary CABG among patients with a low risk of postoperative bleeding, did not result in any significant decrease in postoperative bleeding compared to a placebo group. The application of a pneumatic tourniquet in orthopedic procedures enhances local fibrinolysis. Consequently, a short-term antifibrinolytic therapy may be indicated in this clinical situation to reduce postoperative blood loss. The purpose of this prospective double-blind study was to investigate the effect of tranexamic acid (TA) on blood loss associated with total knee arthroplasty (TKA). Seventy-five patients scheduled for 77 TKAs were randomized to receive either TA (n = 39) or equal volume of normal saline (NS, n = 38). Before deflation of the tourniquet, 15 mg/kg of TA was given intravenously followed by two 10-mg/kg additional doses. Perioperative blood loss gathered in surgical gauzes, suction reservoirs, and postoperative drainage system was measured. The number of transfusions given during hospitalization was registered. Total blood loss (mean +/- SD) was 689 +/- 289 mL in the TA group and 1509 +/- 643 mL in the NS group (P < 0.0001). The mean number of transfused red cell units in the TA group was 1.0 +/- 1.2 compared to 3.1 +/- 1.6 in the NS group (P < 0.0001). Twenty-two patients in the TA group and four patients in the NS group were treated without transfusion (P < 0.00003). Two patients in the TA group and three in the NS group had a deep venous thrombosis, including a fatal case of pulmonary embolism in the NS group. We conclude that short-term TA therapy significantly reduces TKA-associated blood loss and transfusion requirements without increasing thromboembolic complications. To investigate the effects of aprotinin on red cell (RC) immune function in the patients undergoing cardiopulmonary bypass (CPB), 20 patients who received valve replacement procedure were prospectively studied. The patients were randomly assigned to aprotinin group and control group. Red blood cell C3b receptor ratio (RC3bRR), red blood cell immune-component ratio (RICR), plasma C3, C4, CH50 and IgG level were determined before operation, at the end of CPB and 1st, 3rd, 7th postoperative days. Our results showed that: (1) The blood requirement was reduced in aprotinin group. (2) After bypass, plasma C3, C4, CH50 was maintained in aprotinin group, while they declined in control group. (3) Plasma level IgG fell in both groups, but at 7th postoperative day it recovered in aprotinin group while the level stayed at low level in control group. (4) The RC3bRR and RICR was mildly inhibited in aprotinin group. It is concluded that the impairment of RC immune function caused by CPB can be mitigated by aprotinin, which may be related to the effects of aprotinin in blood sparing, restriction of complement activation, and reduction of blood requirement which could mitigate the non-specific inflammatory reaction. We have studied the effect of aprotinin on blood loss and subsequent blood transfusion in 17 patients undergoing knee replacement surgery. Patients receiving aprotinin (total dose 2,000,000 kallikrein inhibiting units) received fewer units of blood than control patients (P < 0.05), although there was no significant difference in blood loss between the two groups. The study was stopped when one patient in the aprotinin group needed an above-knee amputation because of ischaemia secondary to arteriovenous thrombosis after knee replacement surgery. Although the patient had peripheral vascular disease which could have accounted for the thrombosis, the role of aprotinin under tourniquet conditions is unclear. Evaluation of the effect of aprotinin on heparin monitoring tests, on heparin doses, and on perioperative blood loss in patients undergoing coronary artery bypass grafting.
                Randomized, prospective open study.
                The study was performed in the departments of Anaesthesiology and Haematology of the Erasme University Hospital, Brussels.
                Twenty-six patients undergoing primary coronary artery bypass grafting.
                Twelve patients received aprotinin, and 14 received no treatment.
                Aprotinin significantly reduced blood loss during coronary artery bypass surgery and was associated with a slight reduction in the amount of heparin administered. Activated coagulation time and activated partial thromboplastin time were prolonged by the addition of aprotinin. Activated coagulation time and activated partial thromboplastin time were poorly correlated with heparin assays. On the other hand, two other clotting tests designed to monitor heparin therapy, namely Titrarine (Stago, Asnière, France) and Heptest (Haemachem, St. Louis, MO), gave very good correlation with amidolytic heparin assays and can be used during extracorporeal circulation. Thrombin time showed a good correlation with amidolytic heparin assays after protamine administration and can be useful to detect residual heparin after heparin neutralization by protamine. Fibrinolysis has been recognized as an important cause of intraoperative bleeding during orthotopic liver transplantation (OLT). Several investigators have used prophylactic administration of aprotinin in patients to inhibit fibrinolysis and to decrease transfusion requirements, morbidity, and mortality. Nevertheless, the role of aprotinin in this situation is not yet clear. The goal of this study was to determine the effects of prophylactic administration of aprotinin on intraoperative bleeding and blood requirements, and on hemostatic changes during OLT. Eighty consecutive patients were included in a double-blind, prospective study and were randomized in two groups. In group A (n = 39), an initial dose of 2 x 10(6) kallikrein inactivator units (KIU) of aprotinin was administered in the induction of anesthesia followed by infusion of 5 x 10(5) KIU/h until the end of the procedure. The control group (n = 41) received an identical volume of saline solution. The majority of the operations were performed with vena cava preservation (piggy-back technique) without venovenous bypass. During the anhepatic phase, a significant increase in levels of tissue plasminogen activator, thrombin-antithrombin complexes (TAT) and D-dimers (DD) was noted in both groups. A significant increment of TAT was observed in group A during reperfusion. The remaining hemostatic parameters were similar in both groups. Intraoperative requirements of packed red cells, fresh-frozen plasma (FFP), platelets, and cryoprecipitate were similar in the two groups. Our results suggest that prophylactic administration of aprotinin is not useful in reducing bleeding and blood product requirements during OLT. To assess the influence of tourniquet inflation-deflation as well as desmopressin and tranexamic acid (TA) administration on prothrombin fragment 1.2, fibrinogen, plasmin antiplasmin complex, and D-dimer concentrations during total knee replacement.
                Randomized, placebo-controlled study.
                Large referral hospital.
                30 ASA physical status I, II, and III patients undergoing total knee replacement.
                Patients were randomized to one of three treatment groups. Patients received either tranexamic acid, desmopressin, or an equal volume of saline, intravenously.
                Cubital blood was drawn immediately before induction of anesthesia, 1 hour after tourniquet application, and 2 and 15 minutes after tourniquet deflation. Fibrinogen and D-dimer levels were measured using the Clauss Method and latex agglutination, respectively. Plasmin antiplasmin complex and prothrombin fragment 1.2 levels were measured by enzyme-linked immunosorbent assay (ELISA). All assays were performed in duplicate, and intra-assay variability was documented. No statistically significant difference in fibrinogen, D-dimer, plasmin antiplasmin complex, or prothrombin fragment 1.2 levels was demonstrated among the groups. Similarly, within each group there were no statistically significant differences in the variables studied. However, despite the lack of statistical significance, when compared with their levels during tourniquet application, an increase in D-dimer and plasmin antiplasmin complex levels was observed in all three groups at 2 and 15 minutes after tourniquet release. In contrast, no increase in prothrombin fragment 1.2 generation was noted. Significantly more allogeneic blood was transfused in the Control and Desmopressin Groups when compared with the tranexamic acid group (p< 0.02).
                No evidence of tourniquet-induced fibrinolysis or thrombin generation was demonstrated in the systemic circulation. Desmopressin and tranexamic acid had no significant effect on the variables measured. Bleeding remains a major complication and a major determinant in the prognosis of open-heart surgery. Coagulopathy related to cardiopulmonary bypass (CPB) seems to be the culprit. Since homologous blood transfusion in many occasions is not only responsible for mobidity and mortality but also increases medical costs. Therefore, the application of autologous blood transfusion including components such as PRBC, FFP and platelets concentrate is inevitable and comes in its stead. To reduce the use of homologous plasma and platelets transfusion in open-heart surgery, we designed a study to utilize the combination of autologous platelet rich plasma (PRP) and epsilon aminocaproic acid (EACA) to evaluate its effects on blood loss and blood component transfusion in open-heart patients.
                Sixty patients who received elective cardiac surgery were randomly divided into 3 groups: 1. Control group; 2. EACA group (150 mg/kg, i.v. before CPB); 3. PRP-EACA group (PRP 10 ml/kg harvested with a plasma saver followed by i.v. EACA 150 mg/kg). Anesthesia was uniform in all patients. Coagulation profile was evaluated by thromboelastography (TEG) during the operation. Blood loss during operation and the amount of drainage from the chest tubes in the postoperative period were recorded and compared between groups.
                Patients who were given EACA injection before CPB saw less blood loss perioperatively and received less transfusion of blood components. TEG analysis showed that patients who received EACA injection had a better coagulation profile and the platelet function was also better after CPB. However, no additive effect can be attained from combination of autologous PRP transfusion and EACA injection.
                With Pre-CPB EACA as protection, reduction of both blood loss and blood transfusion could be realized in open-heart surgery. Off-pump coronary artery bypass (OPCAB) surgery is associated with a hypercoagulable state in which the platelet thrombin receptor, protease-activated receptor-1 (PAR-1), helps propagate a thrombin burst within saphenous vein grafts. Aprotinin, used in cardiothoracic surgery mainly for its antifibrinolytic properties, also spares platelet PAR-1 activation due to thrombin. We hypothesized that this PAR-1 antagonistic property provides an antithrombotic benefit during OPCAB surgery.
                Patients were randomly assigned to receive saline (n = 38) or a modified full-dose regimen of aprotinin (n = 37) IV during OPCAB surgery. Blood sampled perioperatively from the coronary sinus, skin wounds, and systemic circulation was analyzed to test coagulation and platelet function. Major adverse cardiovascular events were monitored by obtaining troponin I at 24 h (myocardial infarction), predischarge computed tomography angiography (vein graft thrombosis), and by clinical examination for stroke.
                Coronary sinus blood obtained immediately after OPCAB surgery showed significantly less activation in the aprotinin group, as judged by reduced formation of platelet-leukocyte conjugates (P < 0.02) and platelet-derived microparticles (P < 0.05). The aprotinin group showed inhibition of platelet aggregation induced by thrombin (P = 0.007) but not adenosine diphosphate. Thrombin generation, defined by F1.2 levels, was significantly reduced by aprotinin in the coronary sinus but not in skin wound incisions. Major adverse cardiovascular events were significantly reduced in aprotinin-treated patients (5.4% vs 29.7%, P < 0.05). Aprotinin also demonstrated antifibrinolytic properties through diminished red blood cell transfusion (P < 0.04) and reduced blood loss postoperatively (603 +/- 330 vs 810 +/- 415 mL, P < 0.004).
                This study demonstrates that aprotinin protects patients undergoing OPCAB surgery from a hypercoagulable state by diminishing thrombin-induced platelet activation and thrombin generation within saphenous vein grafts, while maintaining systemic hemostatic and antifibrinolytic benefits. These results support further investigation of aprotinin and other PAR-1 antagonists in OPCAB surgery. Sixty patients (four groups of 15 patients) were entered in a randomized, controlled study to compare the efficacy of prophylactic treatment with dipyridamole, tranexamic acid, and aprotinin to reduce bleeding after elective coronary artery bypass grafting. Only patients with a preoperative platelet count of less than 246 x 10(9)/L were selected because a previous study showed that these individuals are at risk for increased postoperative bleeding. Compared to control subjects, postoperative blood loss 6 hours after operation was significantly reduced by tranexamic acid (674 +/- 411 versus 352 +/- 150 mL; p < 0.05) and by aprotinin (270 +/- 174 mL; p < 0.01). Dipyridamole did not reduce postoperative blood loss and was associated with complications in 3 patients. We conclude that hemostasis after cardiac operations can be improved with tranexamic acid and aprotinin. Dipyridamole appeared to be ineffective. To determine whether aprotinin can provide a significant improvement of hemostasis in cardiopulmonary bypass using a membrane oxygenator, we tested this drug in a prospective, randomized, double-blind, placebo-controlled clinical trial. The subjects were 80 male patients undergoing cardiopulmonary bypass for coronary artery bypass grafting. Forty patients received aprotinin and 40 patients served as placebo controls. Aprotinin (4 x 10(6) KIU) was given as a continuous infusion, starting before operation and continuing until after cardiopulmonary bypass; additionally, 2 x 10(6) KIU aprotinin was added to the pump prime. Intraoperative and postoperative bleeding, respectively two thirds and one third of the total perioperative blood loss, were both significantly reduced in the aprotinin-treated group (p less than 0.01). The total average perioperative blood loss, corrected to a hemoglobin concentration of 7 mmol/L, was 550 mL in the aprotinin-treated patients versus 900 mL in the control patients. This reduction in blood loss, furthermore, significantly decreased the amount of postoperative blood transfusions (p less than 0.05) and increased the percentage of patients who did not receive postoperative donor blood from 42% to 68%. Aprotinin increased the activated clotting time significantly during cardiopulmonary bypass, which led to a reduction in heparin usage. The improved hemostasis during operation, despite the prolonged activated clotting time, might even abolish the need for heparin conversion with protamine at the end of cardiopulmonary bypass, thus allowing retransfusion through cardiotomy suction to be continued, which saves the blood that is currently lost with vacuum suction. High-dose aprotinin reduces bleeding after cardiac surgery, but has also evoked concern with regard to potential side effects and hospital costs. To evaluate the effects of reduced-dose aprotinin on blood loss and need for blood transfusion, 40 patients undergoing myocardial revascularization were studied (double-blind, placebo-controlled). Postoperative bleeding was reduced by 40% and erythrocyte infusion by 85% in the group given 3 x 10(6) KIU aprotinin (1 x 10(6) as a loading dose before cardiopulmonary bypass, 1 x 10(6) in the priming volume and 2.5 x 10(5)/hour intraoperatively) Aprotinin concentrations during the operation were monitored and maintained above the required level. There were no adverse effects of the drug. Hospital expenditure on blood products was reduced by 51% when aprotinin was used. Our study suggests that aprotinin in reduced dosage diminishes bleeding and requirements for blood products, and that it should be given before, during and after cardiopulmonary bypass. We have investigated in a prospective,randomised placebo-controlled study the effect of high-dose aprotinin on blood loss in patients admitted for major surgery (revision arthroplasty of the hip or knee, or for resection of a soft-tissue sarcoma). The mean intraoperative blood loss was reduced from 1957 ml in the control group to 736 ml in the aprotinin group (p = 0.002). The mean requirement for intraoperative homologous blood transfusion in the aprotinin group was 1.4 units (95% CI 0.2 to 2.7) and 3.1 units (95% CI 1.7 to 4.6) in the control group (p = 0.033). The mean length of hospital stay was reduced from 27.8 days in the control group to 17.6 days in the aprotinin group which was not statistically significant. The intraoperative use of aprotinin in major orthopaedic operations significantly reduced blood loss and the required amount of packed cells. It may result in in the length of hospital stay and costs. Aprotinin and epsilon-aminocaproic acid are routinely used to reduce bleeding during cardiac surgery. The marked difference in average wholesale cost between these two drug therapies (aprotinin, $1,080 vs. epsilon-aminocaproic acid, $11) has generated significant controversy regarding their relative efficacies and costs.
                In a multicenter, randomized, prospective, blinded trial, patients having repeated cardiac surgery received either a high-dose regimen of aprotinin (total dose, 6 x 10(6) kallikrein inactivator units) or epsilon-aminocaproic acid (total dose, 270 mg/kg).
                Two hundred four patients were studied. Overall (data are median [25th-75th percentiles]), aprotinin-treated patients had less postoperative thoracic drainage (511 ml [383-805 ml] vs. 655 ml [464-1,045 ml]; P = 0.016) and received fewer platelet transfusions (0 [range, 0-1] vs. 1 [range, 0-2]; P = 0.036). The surgical field was more likely to be considered free of bleeding in aprotinin-treated patients (44% vs. 26%; P = 0.012). No differences, however, were seen in allogeneic erythrocyte transfusions or in the time required for chest closure. Overall, direct and indirect bleeding-related costs were greater in aprotinin- than in epsilon-aminocaproic acid-treated patients ($1,813 [$1,476-2,605] vs. $1,088 [range, $511-2,057]; P = 0.0001). This difference in cost per case varied in magnitude among sites but not in direction.
                Aprotinin was more effective than epsilon-aminocaproic acid at decreasing bleeding and platelet transfusions. Epsilon-aminocaproic acid, however, was the more cost-effective therapy over a broad range of estimates for bleeding-related costs in patients undergoing repeated cardiac surgery. A cost-benefit analysis using the lower cost of half-dose aprotinin ($540) still resulted in a significant cost advantage using epsilon-aminocaproic therapy (P = 0.022). Patients with heart disease are frequently maintained on a regimen of aspirin because of its ability to decrease thrombotic complications and reduce the prevalence of unstable angina and myocardial infarction. Aspirin-induced platelet acetylation also increases bleeding caused by impairment of platelet function during cardiac surgery.
                Between October 1990 and November 1991 this double-blind, randomized, placebo-controlled, parallel group interventional study examined the efficacy of high-dose aprotinin administration (up to 7 million KIU) to decrease blood loss and transfusion requirements in patients receiving aspirin within 48 hours of undergoing coronary bypass or valvular heart operations. Primary outcome measures in this study were total volume of blood loss (intraoperative blood loss plus postoperative chest tube drainage) and volume of transfusion during hospitalization.
                Patients treated with aprotinin (n = 29) had significantly lower total blood loss (1409 +/- 232 ml versus 2765 +/- 248 ml; p = 0.0002), intraoperative blood loss (503 +/- 53 ml versus 1055 +/- 199 ml; p = 0.0001), postoperative blood loss (906 +/- 204 ml versus 1710 +/- 202 ml; p = 0.0074), and prevalence of transfusion (59% versus 88% of patients; p = 0.016) than the placebo group (n = 25). The prevalence of complications including myocardial infarction was similar in the two groups.
                High-dose aprotinin significantly reduces blood loss and red blood cell transfusions in patients receiving aspirin who undergo cardiac operations. To verify whether low-dose aprotinin reduces blood loss and blood product usage in patients with clopidogrel exposure within 5 days before off-pump coronary artery bypass, 51 patients with clopidogrel exposure were randomized in a double-blind fashion to receive low-dose aprotinin (25 patients), or placebo (26 patients). The baseline characteristics and number of distal anastomoses in the patients in each group were comparable. Time between the last dose of clopidogrel and start of the operation was similar in both groups, as was mean left ventricular ejection fraction. Chest tube drainage, blood product usage, and reoperation rate were significantly higher in the placebo group. In patients with unstable angina and recent clopidogrel exposure who are undergoing off-pump coronary artery bypass, intraoperative administration of low-dose aprotinin is recommended to reduce blood loss and transfusion requirements. This study compared the transfusion rates of patients treated with heparin-bonded circuits with the transfusion rates of patients treated with standard bypass circuits with and without -aminocaproic acid (EACA).
                Prospective double-blind (drugs), open trial (cardiopulmonary bypass circuits).
                University medical center.
                Seventy-one patients undergoing elective am admission coronary artery bypass graft surgery.
                Patients were randomized to receive either heparin-coated cardiopulmonary bypass circuits (HBCPB), nonheparin-coated cardiopulmonary bypass circuits and EACA (EACPB), or nonheparin-coated bypass circuits and placebo (control). Patients were transfused if their hematocrit was <18% while on cardiopulmonary bypass or <25% at any time after the cardiopulmonary bypass period. The rate and number of transfused packed red blood cells (pRBCs), platelets, fresh frozen plasma, and cryoprecipitate were measured. A Fisher exact test showed that the transfusion rate was as follows: the HBCPB group (5.0%), the EACPB group (18.2%), and the control group (36%), (p = 0.034).
                The heparin-bonded cardiopulmonary bypass-treated patients in this study received fewer pRBCs than did the control group. A nonsignificant reduction in the pRBC transfusion rate was found between those with heparin-bonded bypass circuits and those with standard circuits who received epsilon-aminocaproic acid. The effects of aprotinin combined with heparin-bonded bypass circuits and reduced systemic heparinization on haemostasis and inflammatory reactions were measured in patients with elective CABG operation. Patients were randomized to be operated on either without aprotinin (NOAPRO, n=15) or with aprotinin (APRO, n=15) at a low dose of 2 Mio KIU in the priming volume. Activated clotting time was adjusted to 400 +/- 50 s during cardiopulmonary bypass (CPB). Haemostasis (fibrinopeptide A (FPA), thrombin-antithrombin complex (TAT), D-Dimer, plasmin-antiplasmin (PAP), plasminogen-activator inhibitor (PAI)), inflammatory reaction (lactoferrin, IL-6, sTNF-IIR, SC5b-9) and clinical data were evaluated perioperatively. Perioperative clinical and laboratory data including mediastinal drainage volume, postoperative morbidity and mortality were comparable for patients in both groups. FPA was elevated in the APRO group during CPB (P=0.001), D-Dimer in the NOAPRO group after CPB (P=0.002). No differences were seen for TAT, PAP or PAI between the groups. Lactoferrin was elevated in NOAPRO at the end of CPB (P=0.01) and after heparin reversal with protamine sulphate (P=0.02). No intergroup differences were seen for IL-6, sTNF-IIR or SC5b-9 between the groups. In association with reduced heparinization, pump prime aprotinin retains its antifibrinolytic effect in modified bypass equipment with a heparin surface besides an anti-inflammatory effect in terms of inhibition of leukocyte activation. However, thrombin activation may be increased with aprotinin. We therefore recommend sufficient systemic heparinization despite heparin surface modification of bypass equipment. Spinal reconstructive surgery in adults can be associated with significant blood loss, often requiring allogeneic blood transfusion. The objective of this randomized, prospective, double-blind, multicenter study was to evaluate the efficacy of tranexamic acid (TXA) in reducing perioperative blood loss and transfusion in adult patients having elective posterior thoracic/lumbar instrumented spinal fusion surgery.
                One hundred fifty-one adult patients were randomized to receive either a bolus of 10 mg/kg IV of TXA after induction followed by a maintenance infusion of 1 mg/kg/hr of TXA, or an equivalent volume of placebo (normal saline). The primary outcome was the total perioperative estimated and calculated blood loss intraoperatively and 24 h postoperatively. Secondary outcomes were incidence of allogeneic blood exposure, and duration of hospital stay.
                Four patients were withdrawn for identifiable surgical bleeding, therefore 147 patients were included in the analysis. The total estimated and calculated perioperative blood loss was approximately 25% and 30% lower in patients given TXA versus placebo (1592 +/- 1315 mL vs 2138 +/- 1607 mL, P = 0.026; 3079 +/- 2558 vs 4363 +/- 3030, P = 0.017), respectively. There was no difference in the amounts of blood products transfused, and length of stay between the two groups. TXA, surgical duration, and number of vertebrae fused were independent factors related to perioperative blood loss. Predictors for the need for allogeneic red blood cell transfusion were ASA classification, surgical duration and number of levels fused.
                TXA significantly reduced the estimated and calculated total amount of perioperative blood loss in adult patients having elective posterior thoracic/lumbar instrumented spinal fusion surgery. A blood transfusion is a costly transplantation of tissue that may endanger the health for the recipient. Blood transfusions are common after total hip arthroplasty. The total saving potential is substantial if the blood loss could be reduced. Studies on the use of tranexamic acid have shown interesting results, but its benefits in total hip arthroplasty have not yet been resolved.
                100 patients receiving a total hip arthroplasty (THA) got a single injection of tranexamic acid (15 mg/kg) or placebo intravenously before the start of the operation. The study was double-blind and randomized. Total blood loss was calculated from the hemoglobin (Hb) balance. Volume and Hb concentration of the drainage was measured 24 h after the operation. Intraoperative blood loss was estimated volumetrically and visually.
                The patients who received tranexamic acid (TA) bled less. The total blood loss was on average 0.97 L in the TA group and 1.3 L in the placebo group (p < 0.001). 8/47 (0.2) in the TA group were given blood transfusion versus 23/53 (0.4) in the placebo group (p = 0.009). Drainage volume and drainage Hb concentration were less in the TA group (p < 0.001 and p = 0.001). No thromboembolic complications occurred.
                Considering the cost of blood and tranexamic acid only, use of the drug would save EUR 47 Euro per patient. We recommend a preoperative single dose of tranexamic acid for standard use in THA. To evaluate the effects of minimal-dose aprotinin in patients undergoing coronary artery bypass grafting, we conducted a prospective randomized study.
                A total of 167 patients were randomized to receive no aprotinin treatment (control, n = 57), minimal-dose aprotinin (1.0 x 10(6) KIU; n = 55), or low-dose aprotinin (2.7 +/- 0.5 x 10(6) KIU; n = 55). Blood loss and transfusion requirements, parameters of clotting and fibrinolysis, renal function, and early graft patency rates were assessed.
                Postoperative blood loss and transfusion requirements were significantly (p = 0.01) lower in both the minimal-dose and low-dose groups than in the control group. The increase in D-dimer level after cardiopulmonary bypass was significantly (p < 0.05) less marked in the low-dose group than in the control group. The alpha 2-plasmin inhibitor and plasminogen activator inhibitor-1 levels were significantly (p < 0.05) greater in the minimal-dose and low-dose groups than in the control group after bypass, suggesting the prevention of fibrinolysis by both aprotinin doses. No statistically significant differences in postoperative renal function and early vein graft patency rates were noted (control group, 93.8%; minimal-dose group, 95.5%; low-dose group, 92.3%; p = 0.25).
                Aprotinin was not associated with a significant increase in the prevalence of renal dysfunction or early vein graft occlusion. Minimal-dose aprotinin inhibited enhanced fibrinolytic activity and reduced blood loss and transfusion requirements after bypass equivalently to low-dose aprotinin. The dose of 1 x 10(6) KIU added to the pump prime may be acceptably effective in reducing blood loss in patients undergoing primary coronary operations. Extensive blood loss in total knee replacement (TKR) surgery is well known and is associated with a high transfusion rate of allogenic blood. Tranexamic acid (TXA) has been shown to reduce blood loss by 50% in this patient group, but only in cases with a perioperative loss of 1400-1800 ml. This study was performed to see if TXA offers any advantages in knee replacement surgery with blood loss at 800 ml.
                Thirty consecutive patients scheduled for TKR in spinal anesthesia with the use of a tourniquet, were randomized to TXA or non-TXA. Tranexamic acid 10 mg kg-1 was given at conclusion of surgery and again 3 h later. Blood loss was registered.
                Total blood loss was at all times significantly lower in the TXA group compared to the non-TXA group (409.7+/-174.9 ml vs. 761.7+/-313.1 ml; P<0.001). There were no differences in coagulation parameters. No patients in the TXA group had a blood transfusion vs. 13% in the non-TXA group (NS). No complications were registered in the two groups.
                We conclude that TXA significantly reduces blood loss after total knee replacement surgery. Aprotinin (AP) reduces blood loss and transfusions after cardiopulmonary bypass (CPB), but may sensitise patients and is expensive. Tranexamic acid (TA) has less side-effects, but data regarding its efficacy are controversial. The aim of our prospective, randomised, double-blind study was to compare the impact of AP vs. TA on drainage blood loss and transfusion requirements in patients undergoing first time CABG on CPB.
                One hundred and twenty adult patients were randomised to receive either high-dose AP according to Hammersmith or a total of 2 g TA. Perioperative blood products were transfused in a standardised fashion. Blood loss was measured up to 24 h. Demographic and clinical patient data were collected until hospital discharge.
                The data from 118 patients (TA: n = 58, AP: n = 60) who completed the study according to protocol were analysed. Blood loss at 24 h postoperation in TA patients was significantly higher (896 +/- 354 ml) as compared to AP patients (756 +/- 347 ml; p = 0.03). TA patients received 1.5 +/- 1.5 units of red blood cells (AP: 1.5 +/- 1.7, p = 1.0), 1.3 +/- 2.0 units of fresh frozen plasma (AP: 1.0 +/- 2.0, p = 0.38) and 0.5 +/- 1.4 units of platelets (AP: 0.2 +/- 0.7, p = 0.15). Clinical data, including perioperative myocardial infarction rate, acute renal failure, mechanical ventilation, hospital stay and mortality, were not significantly different between either group.
                Our data show a difference in blood loss between TA and high-dose AP. Although statistically significant, it has little clinical relevance, because perioperative transfusion requirements were similar for both groups. Thus, TA appears to be a cost-effective alternative to AP in primary CABG patients. Studies have shown that aprotinin and tranexamic acid can reduce postoperative blood loss after cardiac operation. However, which drug is more efficacious in a higher risk surgical group of patients, has yet to be defined in a randomized study.
                With informed consent, 80 patients undergoing elective high transfusion risk cardiac procedures (repeat sternotomy, multiple valve, combined procedures, or aortic arch operation) were randomized in a double-blind fashion, to receive either high dose aprotinin or tranexamic acid. Patient and operative characteristics, chest tube drainage and transfusion requirements were recorded.
                There was no significant difference between the 2 treatment groups with respect to age, cardiopulmonary bypass time, complications (myocardial infarction, stroke, death), chest tube drainage (6, 12, or 24 hours), blood transfusions up to 24 hours postoperatively, total allogeneic blood transfusions for entire hospital stay, or induction/postoperative hemoglobin levels. However, multiple regression analysis revealed a positive relationship between cardiopulmonary bypass time and 24 hour blood loss in the tranexamic acid group (p = 0.001), unlike the aprotinin group where 24 hour blood loss is independent of cardiopulmonary bypass time (p = 0.423).
                Overall, there was no significant difference in blood loss, or transfusion requirements, when patients received either aprotinin or tranexamic acid for high transfusion risk cardiac operation. Aprotinin, when given as an infusion in a high-dose regimen, was able to negate the usual positive effect of cardiopulmonary bypass time on chest tube blood loss. To determine a possible phase of hypercoagulability after the use of high-dose aprotinin, a prospective randomized double-blind study was performed. Twenty patients undergoing aortocoronary bypass surgery were investigated, a placebo group P (n = 10) was compared to an aprotinin group A (n = 10). Examining parameters of thrombin activation and fibrinolysis, we found during extracorporeal circulation--under continuous aprotinin infusion--a significant inhibition of thrombin activation and fibrinolysis in the aprotinin group (thrombin-antithrombin-III-complexes: 95 +/- 23 micrograms/l, d-dimers: 448 +/- 60 ng/ml, plasminogen activity: 33 +/- 3%, plasminogen activator inhibitor: 98 +/- 14 U/ml) compared to the placebo group (thrombin-antithrombin-III-complexes: 143 +/- 13 micrograms/l, d-dimers: 2755 +/- 430 ng/ml, plasminogen activity: 125 +/- 15%, plasminogen activator inhibitor: 10 +/- 4 U/ml). In contrast, after stopping the aprotinin infusion--from the end of extracorporeal circulation until the morning of the first postoperative day--strong thrombin activation took place in the aprotinin group (d-dimers increased from 472 +/- 90 to 1607 +/- 140 ng/ml), while in the placebo group a decrease could be registered. At this time, the fibrinolysis was still reduced in the aprotinin group (plasminogen activity: 48 +/- 6% vs 85 +/- 16% in the placebo group). In conclusion, interference with the thrombohemorrhagic balance induces hypercoagulability after the use of high-dose aprotinin, with elevated levels of thrombin-antithrombin-III-complexes, d-dimers, and plasminogen and a decreased level of plasminogen activator inhibitor. In our opinion, it is necessary to prevent this counter-regulation.(ABSTRACT TRUNCATED AT 250 WORDS) We performed a randomized double-blind study on the effect of tranexamic acid on postoperative blood loss and blood transfusions in 39 primary THR operations. Tranexamic acid was given at the end of the operation and 3 hours later. Ultrasound examination 1 week later was performed to measure the occurrence of deep hematomas. In contrast to previous findings in knee arthroplasty, the administration of tranexamic acid failed to give a significant reduction in the postoperative blood loss. This lack of effect was possibly related to the fact that the drug was administered too late. In 11 of the 20 patients receiving tranexamic acid, blood transfusion was not necessary, this being the case in 4/19 in the placebo group (p = 0.05). The occurrence of postoperative deep venous thromboses was similar in the tranexamic acid and placebo groups. To determine whether 500,000 KIU aprotinin is effective to reduce blood loss in coronary artery bypass grafting (CABG) and to evaluate the effects of this regimen on hematologic parameters.
                Forty-four patients scheduled for primary CABG were randomly assigned to the aprotinin (n = 24) or control group (n = 20). In aprotinin group, aprotinin was administered in two equal doses (before skin incision and added to the pump prime). Ventilation time, intensive care unit stay, mediastinal tube drainage, hospitalization, transfusion requirements, and postoperative morbidities and mortality were noted. Hematologic markers of fibrinolytic activity and complement activation were also measured pre- and postoperatively.
                Although less mediastinal drainage occurred in aprotinin group, the difference was not statistically significant. Other postoperative variables like transfusion requirements, morbidities, and mortality were also found to be similar between groups. Among hematologic parameters, only postoperative levels of alpha2-antiplasmin and plasminogen activator inhibitor-1 were significantly higher in aprotinin group.
                Although plasmin inhibitors begin to rise at this very low aprotinin dosage, it is not advisable to use this aprotinin regimen in CABG patients. Tranexamic acid was used to reduce postoperative drainage and allogenic blood transfusion requirements in patients undergoing on-pump primary coronary bypass surgery. Over 12 months, 222 patients participated in this prospective, randomized, placebo-controlled, double-blind study conducted at a tertiary center. Half of the patients were randomly allocated to receive tranexamic acid as a bolus (10 mg x kg(-1)) prior to sternotomy, followed by an infusion (1 mg x kg(-1) x hr(-1)) up to the time of starting of protamine. The other 111 patients received a saline bolus and infusion. Postoperative drainage and transfusion requirements were measured in all patients. Markers of graft patency, hemostasis, hemodynamic stability, and fibrinolysis were evaluated. Chest closure time, renal function parameters, allergic reactions, incidence of stroke, re-exploration, and hospital mortality were also noted. Postoperative drainage was significantly less and blood conservation considerably better when tranexamic acid was used. Post-bypass hemostasis was achieved faster, fibrinolysis was less, and there was no evidence of increased incidence of graft occlusion in the group given tranexamic acid. Cardiopulmonary bypass (CPB) initiates a whole-body inflammatory response where complement and neutrophil activation and cytokine release play an important role. This prospective trial examined the effects of both heparin-coated circuits and aprotinin on the inflammatory processes during CPB, with respect to cytokine release and neutrophil activation.
                Two hundred patients undergoing cardiac surgery were randomized in four groups of 50 patients each: heparin-coated circuit with aprotinin (HCO-A) or without aprotinin (HCO) administration, and uncoated circuit with aprotinin (C-A) or without aprotinin administration (C). In groups receiving aprotinin, a high-dose regimen was given. In all groups, high initial doses of heparin were used (3 mg/kg intravenously). Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-8, and myeloperoxidase and elastase levels were measured in plasma samples taken before, during, and after CPB.
                In all groups, the TNF-alpha, IL-6, and IL-8 levels reached a maximum after protamine administration. After 24 hours, they remained significantly elevated (IL-6 and IL-8) or returned to baseline values (TNF-alpha). A similar pattern was observed with myeloperoxidase and elastase levels. No significant intergroup differences were observed.
                CPB is associated with cytokine release and neutrophil activation, which are not attenuated by the use of heparin-coated circuits or by the administration of aprotinin. Aprotinin and heparin-coated circuits do not show additive effects. Antifibrinolytics are widely used in cardiac surgery to reduce bleeding. Allogeneic blood transfusion, even in primary cardiac operations with low blood loss, is still high. In the present study we evaluated the impact of tranexamic acid compared to aprotinin on the transfusion incidence in cardiac surgical patients with low risk of bleeding.
                This prospective, randomized, double-blind study included 220 patients undergoing primary coronary artery revascularization (coronary artery bypass grafting [CABG]) or aortic valve replacement (AVR). Randomized in blocks of 20, patients received either tranexamic acid (approximately 6 g) or full-dose aprotinin (approximately 5-6 x 10(6) Kallikrein Inhibiting Units). Transfusion was guided by a strict transfusion algorithm. Molecular markers of hemostasis were determined to assess differences in the mode of action of the two drugs. Primary end-points were the incidence of allogeneic red cell transfusion and 24-h postoperative blood loss. Data were analyzed according to the intention-to-treat principle and compared using the chi(2) and Mann-Whitney U-test.
                Two-hundred-twenty patients were enrolled (CABG: 134, AVR: 86). In the aprotinin Group 47% of patients received allogeneic blood during the hospital stay as compared to 61% in the tranexamic acid group (P = 0.036). Aprotinin conferred a 23% reduction in allogeneic transfusion risk (RR 0.77, 95% CI 0.53-0.88). Overall, no significant difference in postoperative bleeding was observed, although 24-h blood loss was reduced in aprotinin-treated CABG patients (500, 350-750 mL vs 650, 475-875 mL (median, 25th-75th percentile); P = 0.039). Despite the lower transfusion rate, the hemoglobin concentration on the first postoperative day was higher in the aprotinin group (11.3, 9.9-12.1 vs 10.6, 9.9-11.6 mg/dL; P = 0.023). The fibrinolytic activity at the end of operation determined by D-Dimer was comparable in both groups. (0.15, 0.11-0.17 mg/L [aprotinin] versus 0.18, 0.12-0.24 mg/L [tranexamic acid]). The activated partial thromboplastin time was prolonged up to 4 h postoperatively in the aprotinin group, while the heparin requirement was reduced: 19% of the patients in the aprotinin group and 45% in the tranexamic acid group received at least one additional bolus heparin during cardiopulmonary bypass (P < 0.001). Troponin T levels postoperatively and on postoperative day 1 were significantly higher in the tranexamic acid group (P = 0.017). No differences in renal, cardiac, or mortality outcomes were observed.
                Considering the rate of transfusion of red blood cells, tranexamic acid was slightly inferior in patients undergoing CABG, but there was no difference in patients receiving AVR. Tranexamic acid seems to be less effective in operations with increased bleeding such as CABG. Clinical benefit depends on specific patient and institution characteristics (ClinicalTrials.gov NCT00396760). Excessive bleeding during and after cardiac surgery with cardiopulmonary bypass is a real problem in this kind of surgery. The use of prophylactic high doses of aprotinin (APROT) reduces blood loss in this context but this treatment is expensive. Some investigators have advocated that epsilon-aminocaproic acid (EACA), a cheaper antifibrinolytic drug, could reduce blood loss in cardiac surgery. The goal of this prospective study was to determine if EACA is as effective as APROT for this clinical condition. Sixty patients undergoing elective surgery for cardiac disease were randomly allocated to one of the two groups. Drugs were administered after induction of anesthesia at a dose of 2.10(6) UIK in the APROT group or 5 g in the EACA group. The same dose was added to the priming of the cardiopulmonary bypass circuit. Until the skin closure the patients received 5.10(5) UIK/h of APROT or 2 g/h of EACA. Bleeding during and after surgery was not different between the two groups. No complication, directly due to the treatment administered, was observed. EACA seems to be as effective as APROT to reduce intra and post cardiac surgery blood loss. EACA has the advantage of being cheaper (treatment is approximately 200 times cheaper), therefore allowing a wider use. Excessive blood loss, as a result of augmented postoperative drainage, is considered one of the most serious cardiosurgical complications. The compounding constitutive anemia seems particularly harmful for patients with coronary artery disease. Aprotinin (Trasylol), a non-specific serine protease inhibitor, is successfully used to reduce excessive postoperative bleeding in such patients. The aim of our study was to verify the hypothesis whether aprotinin used during cardiopulmonary bypass procedure affects hemostatic parameters, which might be crucial for the elevated risk of thromboembolic complications.
                The group of 54 patients subjected to coronary artery surgical treatment included 30 patients, who were given intraoperatively 3 million KIU aprotinin each, and 24 subjects non-treated with aprotinin. Aliquots of blood were withdrawn at several time intervals, until the 5th day after the operation. Whole blood platelet activation and reactivity (the expressions of P-selectin and glycoprotein Ib) were monitored by means of flow cytometry. In addition, several plasma parameters, like PAI-1, t-PA, D-dimers, prothrombin fragment F1 + 2, fibrinogen, ATIII activity, troponin I and CK-MB, as well as platelet count were determined at each time point.
                In this study we confirmed the essential advantage of the use of aprotinin: both the postoperative blood drainage and the blood units to be transfused postoperatively to cardiosurgical patients were vastly reduced in the aprotinin-treated subjects. The enhanced overall frequency of perioperative myocardial infarction events was not attributed to this group of patients, nor the non Q-wave infarctions were observed more often in patients treated with aprotinin. In these patients, fibrinolysis parameters tended to be depressed (with increased PAI-1 dominating over elevated t-PA) on the first day after the operation, and no significant differences with regard to fibrinogen, prothrombin fragment F1 + 2, troponin I and platelet count. There was a continuous rise in D-dimers in all the postoperative patients, which lasted until the third day and tended to reach plateau at the 5th day after the operation. We failed to reveal the preventive effects of aprotinin on platelet function: both platelet activation and reactivity remained apparently unchanged. Overall, our results rather support the reasoning on the advantageous effects of low doses of aprotinin. The use of this inhibitor reduces the risk of postoperative undesirable bleeding and results in a decreased postoperative drainage and reduced transfused blood units. On the other hand, however, a higher incidence of perioperative Q-wave infarction in the aprotinin-treated patients, although purely apparent and not statistically significant, might question the unlimited safety of the use of aprotinin in cardiovascular operations. Tranexamic acid (TA) reduces blood loss in coronary artery surgery with cardiopulmonary bypass. The present prospective study was designed to investigate its hemostatic effect in off-pump coronary artery bypass (OPCAB).
                Seventy-six patients undergoing elective OPCAB were randomized into two groups, received TA (0.75 g loading dose before surgery and 250 mg/h during surgery, gross dose: 1.5 g, n=36) and saline solution (control, n=40), respectively. Perioperative blood samples were collected. Hematochemical parameters including platelet adhesion rate, D-dimer and fibrinopeptide-A (FPA) were analysis. Volume of blood loss, blood transfusion and other clinical data were recorded throughout the perioperative period.
                Cumulative blood loss was significantly reduced in the TA group as compared to the controls postoperatively (6 hrs (median [25th-75th]): TA: 200.0 [140.0-230.0] ml, Control: 225.0 [200.0-347.5.0] ml, p=0.009; 24 hrs: TA: 440.0 [270.0-605.0] ml, Control: 655.0 [500.0-920.0] ml, p<0.001). Number of patients received blood transfusion in each group was similar. Levels of D-dimer rose significantly after surgery, and were significantly lower in the TA group than that in controls. Platelet adhesion rate and FPA levels remained at baseline levels after the operation in two groups. Early clinical outcomes were similar between groups.
                The results indicated that tranexamic acid limits fibrinolysis and reduces blood loss after off-pump coronary artery bypass surgery. One hundred sixty-five patients undergoing primary myocardial revascularization were prospectively entered into a randomized, double-blind, placebo-controlled study, in a single institution, in order to determine the influence of high- and low-dose aprotinin application on early coronary artery bypass graft patency. All patients were operated on by the same team and the three treatment groups were comparable in all demographic data and surgical variables. Postoperative chest tube drainage and transfusion requirements were significantly reduced in patients receiving high or low doses of aprotinin. In all patients vein and internal mammary artery graft patency was assessed by control coronary angiograms 4 to 15 days (median 8.2 days) postoperatively. In the high-dose aprotinin group, 140 of 142 vein grafts and in the low-dose aprotinin group all of the 128 vein grafts were patent compared with 138 of 139 in the placebo group. The difference was not statistically significant (P > 0.05). All pedicled internal mammary artery grafts were patent in the three treatment groups. The prevalence of perioperative myocardial infarction was evaluated by serial creatine kinase-myocardial band (CK-MB) isoenzyme measurements and by electrocardiographic recordings. No additional changes that could be attributed to aprotinin were observed. In conclusion, these results suggest that perioperative myocardial infraction secondary to aprotinin-induced native coronary artery or conduit thrombosis is not increased by aprotinin in patients undergoing primary myocardial revascularization. To evaluate the effect of low-dose aprotinin during cardiopulmonary bypass on platelet function and clinical hemostasis, 30 patients undergoing various cardiopulmonary bypass procedures employing bubble oxygenators were randomized to receive either low-dose aprotinin (2 x 10(6) KIU in the cardiopulmonary bypass priming solution, 15 patients [group A]) or placebo (15 patients [group B]). Blood samples were collected before and after cardiopulmonary bypass to assess platelet count and aggregation on extracellular matrix, which was studied by a scanning electron microscope. On a scale of 1 to 4 preoperative mean platelet aggregation grades were similar in both groups (3.8 +/- 0.5 and 3.5 +/- 0.5 for groups A and B, respectively). Postoperatively, platelet aggregation on extracellular matrix decreased slightly in group A (2.8 +/- 1.3; p < 0.01) and significantly in group B (1.3 +/- 0.5; p < 0.001). Eleven of the 15 patients in group A remained in aggregation grade 3 or 4 compared with none of the group B patients. Platelet count was similar in both groups preoperatively and postoperatively. Total 24-hour postoperative bleeding and blood requirement were lower in the aprotinin group (487 +/- 121 mL and 2.3 +/- 1.0 units) than in the placebo group (752 +/- 404 mL and 6.8 +/- 5.1 units; p < 0.01). These results show that the use of low-dose aprotinin during cardiopulmonary bypass provides improved postoperative hemostasis, which might be related to the protection of the platelet aggregating capacity. Aprotinin is a pharmacological agent which, when given in high doses during cardiopulmonary bypass (CPB), seems to reduce postoperative blood loss significantly and thereby reduces the need for blood transfusion. This study was undertaken to confirm these claims and to show that there was also decreased peroperative bleeding and a shorter operation time. The immediate postoperative clinical course was also assessed. The study was a prospective, randomised double-blind trial versus placebo in 60 coronary patients undergoing at least 2 aorto-coronary bypass grafts for the first time within a 3 month period. During surgery after stopping the CPB the blood loss recorded by aspiration was 49 +/- 61 ml in the aprotinin group and 90 +/- 84 ml in the placebo group (p less than 0.05). The quality of haemostasis in the operated area evaluated independently by the anaesthetist was judged to be excellent in 30 patients in the aprotinin group compared with only 19 in the placebo group (p less than 0.001). The time between coming off CPB and skin closure was significantly shorter in the aprotinin group (42 +/- 10 min versus 49 +/- 12 min) and the dose of protamine injected at the end of the operation was 19 +/- 38 mg in the aprotinin group compared to 43 +/- 46 mg in the placebo group (p less than 0.05). The blood loss recorded over 48 hours in the intensive care unit was nearly three times less in the aprotinin group (380 +/- 125 ml) than with placebo (852 +/- 523 ml).(ABSTRACT TRUNCATED AT 250 WORDS) Cardiopulmonary bypass (CPB) is associated with activation of humoral systems, which results in the release of proteases. These proteases may affect platelets and stimulate granulocytes. In the present study, the protease inhibitor aprotinin was given in high doses to 11 patients to achieve plasma concentrations of more than 150 kallikrein inactivator units per milliliter during CPB. At such concentrations, kallikrein and plasmin are effectively inhibited. This treatment resulted in platelet preservation during CPB. Platelet numbers were virtually unaffected, and thromboxane release was prevented in the aprotinin-treated group in contrast to the control group. Postoperatively, hemostasis was significantly better preserved after aprotinin treatment (blood loss of 357 ml in the treated group versus 674 ml in the untreated group; p less than 0.01). Since tissue-plasminogen activator activity was similar in both groups, the improved hemostasis most likely should be attributed to platelet preservation. Furthermore, aprotinin lessened neutrophilic elastase release, which might contribute to decreased pulmonary dysfunction in patients at risk. The serine proteinase inhibitor aprotinin significantly reduces postoperative blood loss in patients requiring cardiac surgery using cardiopulmonary bypass. This study compared two low-dose regimens with administration of high-dose aprotinin and a control protocol to determine whether the dose of aprotinin could be greatly decreased but still maintain efficacy after primary cardiac surgery. Some 100 patients were randomly assigned to one of four groups: control group (0.9 per cent saline placebo, n = 25); high-dose group (aprotinin 2 x 10(6) kallikrein inactivator (KI) units intravenous patient bolus and 0.5 x 10(6) KI units h-1 plus 2 x 10(6) KI units into pump prime, n = 25); prime group (aprotinin 2 x 10(6) KI units added to the pump prime, n = 24); and patient group (aprotinin 10(6) KI units intravenous patient bolus plus 10(6) KI units added to the pump prime, n = 26). Only patients from the high-dose and patient groups had reduced intraoperative blood loss, but patients from all three aprotinin-treated groups demonstrated a significant decrease in median postoperative blood loss compared with the control group (high-dose 350 ml, prime 420 ml, patient 340 ml versus control 780 ml; P < 0.001). There was an even greater reduction in measured median postoperative haemoglobin loss within the chest drains in the treated compared with the control patients (high-dose 15 g, prime 24 g, patient 14 g versus control 47 g; P < 0.001). These decreases were statistically the same for all the treated groups; it is possible to lower the dose of aprotinin to approximately one-third of the currently recommended dosage and still obtain significantly reduced postoperative blood loss in primary cardiac surgery. Bleeding and inflammation are major complications of extracorporeal circulation. Off-pump coronary artery bypass grafting may reduce the rate of complications, but it can only be applied in selected cases. Pilot studies have shown a potential benefit from the use of antifibrinolytic drugs, but efficacy in randomized double-blind studies evaluating off- and on-pump coronary artery bypass grafting has not been proved.
                We enrolled 102 patients scheduled for on-pump (n = 51) or off-pump (n = 51) coronary artery bypass grafting. Patients were separately double-blind randomly assigned to treatment with tranexamic acid (1 g as 20-minute bolus before skin incision, followed by continuous infusion of 400 mg/h, with 500 mg added to priming in patients undergoing on-pump coronary artery bypass grafting) or placebo (saline solution of equivalent volume). Bleeding in the first 24 postoperative hours was the primary outcome. Requirement for allogeneic transfusions, thrombotic complications, outcomes, and monitoring of coagulation, fibrinolysis, and inflammation were also recorded.
                Tranexamic acid reduced total postoperative bleeding by 43% in patients undergoing on-pump coronary artery bypass grafting and by 27% in those undergoing off-pump coronary artery bypass grafting (P <.0001), with 80% reduction in bleeding exceeding 600 mL (P <.001), 58% reduction in the requirement for all allogeneic transfusions (P =.07), and no apparent effect on thrombotic complications or outcome. This was associated with a reduction in plasma D-dimer levels (P <.0001), to a greater degree in patients undergoing on-pump coronary artery bypass grafting (P <.0001), and interleukin 6 levels (P <.0001), to a greater degree in patients undergoing off-pump coronary artery bypass grafting (P <.001).
                By affecting fibrinolysis, tranexamic acid significantly reduces bleeding both in off- and on-pump coronary artery bypass grafting and may modulate inflammation in these surgical settings. The effects of epsilon-aminocaproic acid (EACA) and tranexamic acid (TA) on bleeding and allogeneic transfusions, and the cost of pharmacological and transfusional treatment were compared to aprotinin (AP).
                We randomized 210 patients subjected to elective cardiac surgery. Of these, 68 patients received EACA (a bolus of 5 g, an infusion of 2 g/h, and 2.5 g in the priming), 72 patients received TA (a bolus of 1 g, an infusion of 400 mg/h, and 500 mg in the priming), and 70 patients received AP (a bolus of 280 mg, an infusion of 70 mg/h, and 280 mg in the priming). Postoperative blood loss and homologous transfusions were collected and the cost of pharmacological treatment and homologous transfusions were calculated.
                Bleeding but not allogeneic transfusions was significantly higher in the EACA group (467+/-234 versus TA, 311+/-231 versus AP, 283+/-233; p < 0.001). Costs of pharmacological and transfusional treatment were significantly lower in the TA group ($58.10+/-$105.10) versus the EACA group ($100.70+/-$158.60) versus the AP group ($432.60+/-$118.70) (p < 0.0001).
                Compared to AP, TA has the same effects on bleeding and transfusions, but with a significant reduction of costs. Patients treated with EACA showed a significantly higher postoperative bleeding with an increased trend of transfusion requirement. We evaluated the hemostatic effects of tranexamic acid, a synthetic antifibrinolytic drug, in patients undergoing beating-heart coronary surgery.
                Forty consecutive patients were in a double-blind manner, prospectively randomized into two groups: 20 patients received tranexamic acid (bolus of 1 g before skin incision, followed by continuous infusion of 400 mg/hr during surgery), and 20 patients received saline. As primary outcomes, bleeding and allogeneic transfusions were considered. D-dimer and fibrinogen plasma levels were also evaluated to monitor the activation of fibrinolysis. Major postoperative thrombotic events, as a potential consequence of antifibrinolytic treatment, were recorded.
                The treatment group had significantly lower postoperative bleeding (median [25th to 75th percentiles]: 400 mL [337 to 490 mL] vs 650 ml [550 to 862 mL], p < 0.0001), lower need for allogeneic blood products (1,200 vs 5,300 mL, p < 0.001), and lower postoperative D-dimer plasma levels. No postoperative thrombotic complications were observed in either group.
                In this initial series of patients undergoing off-pump coronary surgery, tranexamic acid appears to be effective in reducing postoperative bleeding and the need for allogeneic blood products. Since excessive fibrinolysis during cardiac surgery is frequently associated with abnormal perioperative bleeding, many authors have advocated prophylactic use of antifibrinolytic drugs to prevent hemorrhagic disorders. We compared the effects of tranexamic acid (a synthetic antifibrinolytic drug) with aprotinin (a natural derivative product with antifibrinolytic properties) on perioperative bleeding and the need for allogeneic transfusions.
                In a single-center prospective randomized unblinded trial, 1040 consecutive patients undergoing primary, elective cardiac operations with cardiopulmonary bypass received either high-dose aprotinin or tranexamic acid. The aprotinin group (518 patients) received 280 mg in 20 minutes before the skin incision, 280 mg in the priming solution of the extracorporeal circuit, and a continuous infusion of 70 mg/h throughout the operation. The tranexamic acid group (522 patients) received 1 g in 20 minutes before the skin incision, 500 mg in the priming solution of the extracorporeal circuit, and a continuous infusion of 400 mg/h during the operation. Postoperative bleeding, perioperative transfusions, and hematologic variables were evaluated at fixed times. Postoperative thrombotic complications, intubation time, intensive care unit stay, and hospital stay were recorded.
                Postoperative bleeding was similar in the 2 groups: aprotinin 250 mL (150-400 mL) versus tranexamic acid 300 mL (200-450 mL) (median and 25th-75th quartiles), median difference of 50 mL (95% confidence intervals, 0-50 mL). The number of transfusions and the outcome did not differ.
                Tranexamic acid and aprotinin show similar clinical effects on bleeding and allogeneic transfusion in patients undergoing primary elective heart operations. Since tranexamic acid is about 100 times cheaper than aprotinin, its use is preferable in this type of patient. A randomized, placebo-controlled, double-blind trial (n= 15 in each group) showed that patients given aprotinin intravenously (200 ml, [2000000 kallikrein inactivator units] before the operation and then 50 ml per h until the end of the operation) during simultaneous maxillary Le Fort 1 and mandibular sagittal split osteotomies, lost 52% less blood than controls (calculated by subtracting the volume of saline irrigant used from the volume of blood collected in the aspirator bottle and surgical drains). Patients given aprotinin lost a mean (SD) of 473 (190) ml compared with 986 (356) ml in controls. They also required significantly less transfused blood (1 was given 2 units in the aprotinin group compared with 9 given a mean of 1.5 units (range 1-4) in the control group). There were no complications attributable to this drug.
                Copyright 2001 The British Association of Oral and Maxillofacial Surgeons. Aprotinin has been reported to reduce blood loss and transfusion requirements in patients having major orthopedic operations. Data on whether epsilon amino-caproic acid (EACA) is effective in this population are sparse.
                Sixty-nine adults with malignancy scheduled for either pelvic, extremity or spine surgery during general anesthesia entered this randomized, double-blind, placebo-controlled trial, and received either intravenous aprotinin (n = 23), bolus of 2 x 10(6) kallikrein inactivator units (KIU), followed by an infusion of 5 x 10(5) KIU/h, or EACA (n = 22), bolus of 150 mg/kg, followed by a 15 mg/kg/h infusion or saline placebo (n = 24) during surgery. Our goal was to determine whether prophylactic EACA or aprotinin therapy would reduce perioperative blood loss (intraoperative + first 48h) >30% when compared to placebo.
                The mean age of the study population was 52 +/- 17 yr. The groups did not differ in age, duration of surgery, perioperative blood loss or number of packed erythrocyte units transfused. When compared to the placebo group, the two treated groups had a significantly lower D-Dimer level immediately after surgery, P < 0.01.
                Under the conditions of this study, we were unable to find a clinical benefit to using aprotinin or EACA to reduce perioperative blood loss or transfusion requirements during major orthopedic surgery in cancer patients. To determine the effects of prophylactic treatment with EACA for blood loss after cardipulmonary bypass surgery, 350 consecutive patients undergoing open-heart surgery were studied. One hundred seventy patients received an initial dose of 5 g of EACA prior to skin incision, followed by intravenous administration of 1 g/h for the next 6 to 8 h. The control group received saline solution in the same fashion. The EACA-treated group had decreased chest tube blood loss 24 h postoperatively. In addition, EACA-treated patients had fewer myocardial infarctions, cerebrovascular accidents or reoperations for bleeding. Treated patients needed fewer units of blood transfusions than the nontreated group. There was no incidence of hyperthrombotic state or other side effects in the EACA-treated group. We concluded that prophylactic treatment with EACA for open-heart surgery requiring extracorporeal circulation may reduce the total blood loss and the number of blood transfusions in a safe and tolerable manner. Administration of aprotinin during extracorporeal circulation reduces blood loss and improves platelet function.
                To evaluate the protective effect of aprotinin on platelets, 50 patients undergoing cardiopulmonary bypass were randomized before surgery to one of three groups. Seventeen patients (group A) received continuous high-dose aprotinin (7 x 10(6) KIU) during cardiopulmonary bypass, 17 (group B) received a single bolus of aprotinin in the pump prime (2 x 10(6) KIU), and 16 (group C) received placebo. Scanning electron microscopy was used to evaluate platelet aggregation on extracellular matrix. The platelet function was graded from 1 to 4, with grade 4 being normal aggregation. Immediately after cardiopulmonary bypass, 16 patients in group A (94%) reached preoperative aggregation grade (mean grade, 3.4 +/- 0.7) compared with nine of 17 in group B (52%) (mean grade, 2.9 +/- 1.2), and none in group C (0%) (mean grade, 1.4 +/- 0.5; p < 0.001). Postoperative platelet count did not differ significantly among the three groups. After surgery, group A bled less than groups B and C (395 +/- 120 versus 488 +/- 135 and 780 +/- 408 ml, respectively; p < 0.01). Patients in the aprotinin groups received fewer red blood cell units (0.9 +/- 1.2 and 1.9 +/- 1.2 versus 3.4 +/- 1.9, respectively; p < 0.01) and were exposed to less homologous blood products (1.3 +/- 1.7 and 2.1 +/- 1.1 versus 6.1 +/- 5, respectively; p < 0.001).
                By preserving platelet function, aprotinin improves postoperative hemostasis in all patients who receive high dose and in most who receive low dose. Aprotinin has recently been shown to reduce postoperative bleeding and transfusion requirements associated with coronary artery bypass grafting. One concern with its use, however, is that it may have a deleterious effect on graft patency because it promotes hemostasis. Forty-seven patients undergoing coronary artery bypass. Forty-seven patients undergoing coronary artery bypass grafting were enrolled in a prospective, randomized double-blind trial of aprotinin to determine the effect of this agent on postoperative bleeding, transfusion requirements, renal function, and graft patency. The study group was comprised of the 32 patients who underwent technically adequate ultrafast CT scans 6 to 8 weeks postoperatively to determine graft patency. Sixteen patients received aprotinin (aprotinin group) and 16 received placebo (control group).
                Demographic and operative descriptors were comparable between groups. Postoperative mediastinal and chest tube drainage in the aprotinin group was significantly less than that in the control group (722 vs 1,540 mL; p = 0.0006) and the mean blood transfusion requirements were less, but this did not reach significance (125 vs 297 mL; p = 0.42). Analysis of graft patency by patients revealed that 5 patients in the aprotinin group (31%) had at least one occluded graft, while none of the patients in the control group had an occluded graft (p = 0.04). Analysis by graft revealed that 38 of 43 grafts placed in the aprotinin group were patent, while all 38 grafts placed in the placebo group were patent (88.4 vs 100%; p = 0.057). There was no difference in the incidence of myocardial infarction, renal dysfunction or hematologic indexes at discharge between the groups, or evidence of other thrombotic complications.
                We conclude that high-dose aprotinin is effective in reducing hemorrhage after coronary artery bypass grafting. However, its routine use should be approached cautiously due to its possible adverse effects on graft patency. Excessive postoperative bleeding after heart operations continues to be a source of morbidity. This prospective double-blind study evaluated epsilon-aminocaproic acid as an agent to reduce postoperative bleeding and investigated its mode of action. One hundred three patients were randomly assigned to receive either 30 gm epsilon-aminocaproic acid (51 patients) or an equivalent volume of placebo (52 patients). In a subset of these patients (14 epsilon-aminocaproic acid, 12 placebo), tests of platelet function and fibrinolysis were performed.
                By multivariate analysis, three factors were associated with decreased blood loss in the first 24 hours after operation: epsilon-aminocaproic acid versus placebo (647 ml versus 839 ml, p = 0.004), surgeon 1 versus all other surgeons (582 ml versus 978 ml, p = 0.002), and no intraaortic balloon versus intraaortic balloon pump use (664 ml versus 1410 ml, p = 0.02). No significant differences in platelet function could be demonstrated between the two groups. Inhibited fibrinolysis, as reflected by less depression of the euglobulin clot lysis and no rise in D-dimer levels, was significant in the epsilon-aminocaproic acid group compared with the placebo group.
                The intraoperative use of epsilon-aminocaproic acid reduces postoperative cardiac surgical bleeding. Aprotinin is a broad-spectrum serine protease inhibitor that has been shown to attenuate the systemic inflammatory response in patients undergoing cardiac surgery with cardiopulmonary bypass. Although epsilon-aminocaproic acid is similar to aprotinin in its ability to inhibit excessive fibrinolysis (ie, plasmin activity and D-dimer formation), its ability to influence proinflammatory cytokine production remains unclear. This study was designed to compare the effects of epsilon-aminocaproic acid and aprotinin on plasma levels of interleukin-6 and interleukin-8 during and after cardiopulmonary bypass.
                Sixty patients were randomized in a double-blind fashion to receive epsilon-aminocaproic acid, aprotinin, or saline (placebo) in similar dosing regimens (loading dose, pump prime, and infusion). Arterial blood samples were collected before, during, and after cardiopulmonary bypass, and plasma levels of D-dimer, interleukin-6, and interleukin-8 were measured. Data were analyzed using repeated measures analysis of variance.
                Both epsilon-aminocaproic acid and aprotinin administration resulted in significant (P <.05) reductions in D-dimer and interleukin-8 levels compared with saline. These reductions in D-dimer and interleukin-8 levels did not differ between the 2 drug-treated groups. The effect of these two antifibrinolytic agents on interleukin-6 was qualitatively similar to that noted with interleukin-8 but did not reach statistical significance.
                When dosed in a similar manner, epsilon-aminocaproic acid seems to be as effective as aprotinin at reducing interleukin-6 and interleukin-8 levels in patients undergoing primary coronary artery bypass graft surgery. These data indicate that suppression of excessive plasmin activity or D-dimer formation or both may play an important role in the generation of proinflammatory cytokines during and after cardiopulmonary bypass. : Randomized, placebo-controlled trial.
                : To evaluate the efficacy of epsilon aminocaproic acid (EACA) to reduce the number of red-cell (RBC) transfusions in adult patients undergoing major spinal surgery.
                : Reconstructive spinal surgery is associated with significant blood loss. The number of studies evaluating the efficacy of EACA in adult patients undergoing spinal surgery remains scarce and limited.
                : EACA (100 mg/kg) or placebo was administered to 182 adult patients after the induction of anesthesia followed by an infusion that was continued for 8 hours after surgery. Primary end points included total allogeneic RBC transfusions through postoperative day 8 and postoperative allogeneic plus autologus RBC transfusions through postoperative day 8.
                : Mean total allogeneic RBC transfusions were not statistically different between the groups (5.9 units EACA vs. 6.9 units placebo; P = 0.17). Mean postoperative RBC transfusions in the EACA group was less (2.0 units vs. 2.8 units placebo; P = 0.03). There was no significantdifference in mean estimated intraoperative estimated-blood loss (2938 cc EACA vs. 3273 cc placebo; P = 0.32). Mean intensive care unit length of stay was decreased (EACA: 1.8 days vs. 2.8 days placebo; P = 0.04). The incidence of thromboembolic complications was similar (2.2% EACA vs. 6.6% placebo; P = 0.15).
                : The difference in total allogeneic RBC transfusions between the groups was not statistically significant. EACA was associated with a 30% (0.8 units) reduction in postoperative RBC transfusions and a 1-day reduction in ICU LOS, without an increased incidence of thromboembolic events. EACA may be considered for patients undergoing major spinal surgery. Larger studies are needed to evaluate the relationship between EACA and total RBC requirements. Extracorporeal circulation induces hemostatic alterations that lead to inflammatory response (IR) and postoperative bleeding. Tranexamic acid (TA) reduces fibrinolysis and blood loss after cardiopulmonary bypass (CPB). However, its effects on IR and vasoplegic shock (VS) are not well known and elucidating these effects was the main objective of this study.
                A case control study was carried out to determine factors associated with IR after CPB. Patients undergoing elective CPB surgery were randomly assigned to receive 2 g of TA or placebo (0.9% saline) before and after intervention. We performed an intention-to-treat analysis, comparing the incidence of IR and VS. We also analyzed several biological parameters related to inflammation, coagulation, and fibrinolysis systems. We used SPSS version 12.2 for statistical purposes.
                In the case control study, 165 patients were studied, 20.6% fulfilled IR criteria, and the use of TA proved to be an independent protective variable (odds ratio 0.38, 95% confidence interval 0.18 to 0.81; P < 0.01). The clinical trial was interrupted. Fifty patients were randomly assigned to receive TA (24) or placebo (26). Incidence of IR was 17% in the TA group versus 42% in the placebo group (P = 0.047). In the TA group, we observed a significant reduction in the incidence of VS (P = 0.003), the use of norepinephrine (P = 0.029), and time on mechanical ventilation (P = 0.018). These patients showed significantly lower D-dimer, plasminogen activator inhibitor 1, and creatine-kinase levels and a trend toward lower levels of soluble tumor necrosis factor receptor and interleukin-6 within the first 24 hours after CPB.
                The use of TA attenuates the development of IR and VS after CPB. Aprotinin therapy is now widely used during cardiac surgery. This study examined the clinical and economic effectiveness of high-dose or low-dose aprotinin in comparison to placebo.
                In a double blind, randomized study, three groups of 50 patients received high-dose aprotinin costing AUS$614 per patient (AUS$ = Australian dollars), low-dose aprotinin costing AUS$220 per patient or placebo. Resource use influenced by aprotinin therapy was measured.
                Both doses were effective in reducing chest drainage and postoperative transfusion requirements, high-dose being more effective than low-dose. Both doses reduced the rate of reoperations for hemostasis. A base case of statistically significant differences associated with the high-dose and low-dose aprotinin showed cost savings of AUS$77 and AUS$348 per patient, respectively. If the demonstrated less significant reductions in operating room and ward stay are included, these savings become AUS$463 and AUS$715, respectively. Alternately, if cross-matches are replaced by group-and-hold and cell savers are not used, the savings per patient would be AUS$196 and AUS$467, respectively.
                While high-dose aprotinin is clinically more effective than low-dose aprotinin, low-dose therapy demonstrates greater cost savings. Thrombin formation during cardiac surgery could result in disordered hemostasis and thrombosis. The aim of the study was to examine the effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic activity in patients undergoing cardiac surgery.
                Data were collected prospectively from 60 patients undergoing coronary artery bypass grafting using cardiopulmonary bypass (CPB). In a randomized sequence, 20 patients received aprotinin, 20 patients received tranexamic acid, and in 20 patients placebo was used.
                Significant thrombin activity was found in all the studied patients. Thrombin generation was less in the aprotinin group than in the tranexamic acid and the placebo group (thrombin/anti-thrombin III complexes 33.7 +/- 3.6, 53.6 +/- 7.0 and 44.2 +/- 5.3 microg/l 2 h after CPB and F1 + 2 fragment 1.50 +/- 0.10, 2.37 +/- 0.37 and 2.04 +/- 0.20 nmol/l 6 h after surgery, respectively). The inhibition of fibrinolysis was significant with both anti-fibrinolytic drugs (D-dimers 0.427 +/- 0.032, 0.394 +/- 0.039 and 2.808 +/- 0.037 mg/l 2 h after CPB, respectively). The generation of d-dimers was inhibited until 16 h after CPB in the aprotinin group. The plasminogen activation was significantly less in the aprotinin group (plasmin/anti-plasmin complexes 0.884 +/- 0.095, 2.764 +/- 0.254 and 1.574 +/- 0.185 mg/l 2 h after CPB, respectively).
                Thrombin formation is inevitable in coronary artery bypass surgery when CPB is used. The suppression of fibrinolytic activity, either with aprotinin or with tranexamic acid interferes with the hemostatic balance as evaluated by biochemical markers. Further investigations are needed to define the role of hemostatic activation in ischemic complications associated with cardiac surgery. Antifibrinolytic medications administered before skin incision decrease bleeding after cardiac surgery. Numerous case reports indicate thrombus formation with administration of epsilon-aminocaproic acid (epsilon-ACA). The purpose of this study was to examine the efficacy of epsilon-ACA administered after heparinization but before cardiopulmonary bypass in reducing bleeding and transfusion requirements after primary coronary artery bypass surgery.
                Seventy-four adult patients undergoing primary coronary artery bypass surgery were randomized to receive 125 mg/kg epsilon-ACA followed by an infusion of 12.5 mg x kg(-1) x h(-1) or an equivalent volume of saline. Coagulation studies, thromboelastography, and platelet aggregation tests were performed preoperatively, after bypass, and on the first postoperative day. Mediastinal drainage was recorded during the 24 h after surgery. Homologous blood transfusion triggers were predefined and transfusion amounts were recorded.
                One patient was excluded for surgical bleeding and five patients were excluded for transfusion against predefined criteria One patient died from a dysrhythmia 2 h postoperatively. Among the remaining 67, the epsilon-ACA group had less mediastinal blood loss during the 24 h after surgery, 529+/-241 ml versus 691+/-286 ml (mean +/- SD), P < 0.05, despite longer cardiopulmonary bypass times and lower platelet counts, P < 0.05. Platelet aggregation was reduced in both groups following cardiopulmonary bypass but did not differ between groups. Homologous blood transfusion was similar between both groups.
                Prophylactic administration of epsilon-ACA after heparinization but before cardiopulmonary bypass is of minimal benefit for reducing blood loss postoperatively in patients undergoing primary coronary artery bypass grafting. The aim of this study was to determine the safety and efficacy of prophylactic high-dose intravenous aprotinin in reducing intraoperative blood loss in the neurosurgical population.
                A randomized, double-blind, placebo-controlled trial was conducted in parallel groups in two regional neurosurgical departments. One hundred patients with a preoperative diagnosis of intracranial meningioma or vestibular schwannoma subsequently confirmed on histological studies were included. All patients were older than 18 years of age, pregnancy had been excluded, there was no history of bleeding diathesis, no previous exposure to aprotinin, and no ingestion of antiplatelet or anticoagulant medications within the 2 weeks preceding surgery. Aprotinin was administered in doses of 30,000 kallikrein-inhibiting units (KIU)/kg body weight on induction of anesthesia and was continued as an infusion of 10,000 KIU/kg/hr until surgery was complete, or for a maximum of 8 hours. Intraoperative blood loss, blood transfusion, the Glasgow Outcome Scale score, and the Index of Independence were measured, and screening for deep vein thrombosis and the Mini-Mental State Examination were performed.
                Intraoperative blood loss was reduced from 1014 ml (geometric mean) to 508 ml (p = 0.028). Although this study was not designed to evaluate the need for blood transfusion, 37 U of blood was used in 11 patients in the aprotinin group and 58 U in 13 patients in the placebo group (not significant). There were no significant differences in postoperative thrombotic risk or other outcome measures between treatment groups. Aprotinin therefore can be safely used to reduce intraoperative blood loss in patients who are not receiving anticoagulation therapy. Use of antifibrinolytic agents reduces the risk of bleeding and decreases the need for blood product use in patients undergoing cardiac surgery. The purpose of this study was to determine whether perioperative use of tranexamic acid decreases the rate of saphenous vein graft patency in the early postoperative period after conventional coronary artery bypass grafting surgery.
                A total of 312 patients scheduled for elective coronary artery bypass grafting surgery with cardiopulmonary bypass were randomized to receive either tranexamic acid 100 mg/kg (n = 147) or placebo (n = 165) in a double-blinded fashion before the initiation of cardiopulmonary bypass. Saphenous vein graft patency was assessed with magnetic resonance imaging 5 to 30 days after surgery.
                Both groups were comparable with respect to baseline demographic data and surgical characteristics. A total of 237 (76%) patients underwent magnetic resonance imaging assessment. A total of 297 saphenous vein grafts were performed and 253 (85.2%; 95% confidence interval, 83.5%-86.9%) were seen in the tranexamic acid group, and 265 saphenous vein grafts were performed and 231 (87.2%; 95% confidence interval, 85.5%-88.9%) were seen in the placebo group (P = .4969). The blood loss and blood product transfusion rates in the tranexamic acid group were significantly lower than in the placebo group. There was no difference between groups with respect to postoperative morbidity and mortality.
                The administration of tranexamic acid before cardiopulmonary bypass did not seem to compromise early venous graft patency rates but reduced perioperative blood product transfusion rates. Consequently, tranexamic acid could be advocated for routine use in patients undergoing conventional coronary artery bypass grafting surgery. The administration of aprotinin during cardiopulmonary bypass (CPB) is hypothesized to decrease activation of leukocytes and platelets and possibly reduce their adhesion. Although epsilon-aminocaproic acid (EACA) shares the ability of aprotinin to inhibit excessive plasmin activity after CPB, its effect on leukocyte and platelet activation and leukocyte-platelet (heterotypic) adhesion is largely unknown. This study was performed to determine the relative effectiveness of the antifibrinolytics, aprotinin and EACA, at reducing leukocyte and platelet activation and leukocyte-platelet conjugate formation in patients undergoing CPB.
                Thirty-six patients scheduled to undergo cardiac surgery with CPB were randomized in a double-blind fashion to receive EACA, aprotinin, or saline (placebo). Markers of plasmin activity (D-dimer concentrations), platelet activation (CD62P), leukocyte activation (CD11b), and leukocyte-platelet adhesion (monocyte- and neutrophil-platelet conjugates) were measured before, during, and after CPB.
                Platelet CD62P (P-selectin), monocyte CD11b, and monocyte-platelet conjugates were all significantly increased (compared with baseline) in the saline group during and after CPB. Despite equivalent reductions in D-dimer formation in patients receiving EACA (P < 0.0001) and aprotinin (P < 0.0001), decreases in platelet CD62P and monocyte CD11b expression were incomplete (not significantly different from saline control). In contrast, peak monocyte-platelet conjugate formation was significantly reduced by both EACA (P = 0.026) and aprotinin (P = 0.039) immediately after CPB.
                EACA seems to be as effective as aprotinin at reducing peak monocyte-platelet adhesion after CPB. Furthermore, inhibition of excessive plasmin activity seems to influence monocyte-platelet adhesion. The findings suggest that monocyte-platelet conjugate formation may be a useful marker of monocyte and platelet activation in this clinical setting. Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding and to reduce exposure to blood products. We sought to determine whether aprotinin was superior to either tranexamic acid or aminocaproic acid in decreasing massive postoperative bleeding and other clinically important consequences.
                In this multicenter, blinded trial, we randomly assigned 2331 high-risk cardiac surgical patients to one of three groups: 781 received aprotinin, 770 received tranexamic acid, and 780 received aminocaproic acid. The primary outcome was massive postoperative bleeding. Secondary outcomes included death from any cause at 30 days.
                The trial was terminated early because of a higher rate of death in patients receiving aprotinin. A total of 74 patients (9.5%) in the aprotinin group had massive bleeding, as compared with 93 (12.1%) in the tranexamic acid group and 94 (12.1%) in the aminocaproic acid group (relative risk in the aprotinin group for both comparisons, 0.79; 95% confidence interval [CI], 0.59 to 1.05). At 30 days, the rate of death from any cause was 6.0% in the aprotinin group, as compared with 3.9% in the tranexamic acid group (relative risk, 1.55; 95% CI, 0.99 to 2.42) and 4.0% in the aminocaproic acid group (relative risk, 1.52; 95% CI, 0.98 to 2.36). The relative risk of death in the aprotinin group, as compared with that in both groups receiving lysine analogues, was 1.53 (95% CI, 1.06 to 2.22).
                Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative mortality trend associated with aprotinin, as compared with the lysine analogues, precludes its use in high-risk cardiac surgery. (Current Controlled Trials number, ISRCTN15166455 [controlled-trials.com].).
                Copyright 2008 Massachusetts Medical Society. We investigated the effect of a fibrinolytic inhibitor, tranexamic acid, on blood loss and blood transfusion in knee arthroplasty by a randomised, double-blind study of 86 patients. A dose of 10 mg/kg body-weight of either tranexamic acid or placebo was given intravenously shortly before the release of the tourniquet, and repeated three hours later. The mean total blood loss was 730 +/- 280 ml in the tranexamic acid group as against 1410 +/- 480 ml in the placebo group (p < 0.001). Both the number of patients receiving blood transfusion and the number of blood units transfused were reduced to one-third in the treated group, and mean postoperative Hb concentrations were significantly higher after prophylaxis. The number of thromboembolic complications was the same in both groups. Tranexamic acid should be given prophylactically in order to be effective. Fifty patients undergoing primary coronary artery bypass surgery and 50 patients undergoing valve surgery received either high-dose aprotinin (2 million units loading dose, 2 million units added to the CPB prime, and 500,000 units/hr maintenance infusion) or placebo. Mean postoperative blood loss in the first six hours was reduced from 321 ml in the placebo group to 172 ml in the aprotinin group (95% confidence interval (CI) for difference = 95 to 189 ml). Seven patients in the placebo group and 16 patients in the aprotinin group did not require transfusion with homologous blood. This study adds to the growing body of evidence that the administration of high-dose aprotinin reduces blood loss and blood transfusion requirements associated with primary cardiac surgery. We performed a randomized, double-blind study on the effect of tranexamic acid on blood loss and blood transfusions in 40 primary total hip arthroplasties. Tranexamic acid, 10 mg/kg body weight, or placebo, was given intravenously just before the operation. Blood loss during the operation and postoperatively into the drains was recorded, as also were blood hemoglobin concentrations. Ultrasound examination 1 week postoperatively was done to estimate the blood loss due to remaining hematomas. Total (operation + drain) blood loss was 0.76 (95 CI 0.63-0.89) L in the tranexamic acid group as compared to 1.0 (CI 0.81-1.2) L in the placebo group (p = 0.03). The number of blood transfusions during the day of operation was 2 vs. 10 (p = 0.07) and the total number during the hospital stay was 5 vs. 13 (p = 0.2). 1 patient in each group had a pulmonary embolism. Postoperative bleeding still remains a serious problem in bypass surgery. This study evaluated fibrinolysis and perioperative low-dose antifibrinolytic regimens adjusted to the time course of fibrinolysis.
                In a prospective, randomized study of 42 patients undergoing bypass grafting, patients received low-dose aprotinin (group A; n = 14) or low-dose tranexamic acid (group TA; n = 14) intraoperatively and postoperatively, respectively, with no antifibrinolytics for comparison (group C; n = 14). Parameters of procoagulation, fibrinolysis, and activated factor VII were measured preoperatively, intraoperatively, and postoperatively. Blood loss was determined up to 24 hours.
                The level of thrombin-antithrombin III complex was significantly decreased postoperatively in the treatment groups (group A and TA versus C: 25 +/- 14 and 19 +/- 10 microg/L, respectively, versus 40 +/- 21 microg/L; p < 0.05). Levels of plasmin-antiplasmin complexes were significantly decreased postoperatively in group A (607 +/- 231 microg/L) versus group C (825 +/- 225 microg/L) (p < 0.05) but were increased in group TA (1,145 +/- 394 microg/L) versus group C (p < 0.05). At all times intraoperatively and postoperatively, levels of D-dimers were significantly decreased in group A and group TA versus control (p < 0.001), indicating that fibrinolysis persists after the operation. Intraoperatively, the factor VIIa level decreased significantly in group A (20 +/- 8 mU/mL) versus group C (31 +/- 15 mU/mL) (p < 0.05), but not in group TA (32 +/- 15 mU/mL). Blood loss was significantly lower in group A (135 +/- 37 mL) and group TA (155 +/- 71 mL) versus group C (354 +/- 170 mL) (p < 0.001).
                This low-dose aprotinin regimen adjusted to perioperative fibrinolysis reduces blood loss significantly in coronary bypass grafting. For further progress in this subject, clinical investigations of individual fibrinolysis-adjusted antifibrinolytic treatment seems warranted. To assess the ability of tranexamic acid, compared with an untreated control group, to decrease bleeding and transfusion requirements in patients undergoing coronary artery bypass grafting on the beating heart.
                Forty-nine randomly selected patients were enrolled to elective coronary artery bypass grafting without the use of cardiopulmonary bypass. Of these, 23 received tranexamic acid (bolus of 1 g before surgical incision, followed by infusion 200 mg/hour during surgery) and 26 patients were enrolled into a control group. Preoperative hematological variables, postoperative blood loss at 4 and 24 hours, transfusion requirements of packed red blood cells,and postoperative thrombotic events such as a myocardial infarction, stroke and pulmonary embolism were recorded.
                The two groups were similar in terms of patients' characteristics. Postoperative bleeding was significantly lower in the tranexamic acid group compared with the control group (median [25th-75th percentiles]): 115 [92-148] vs 230 [170-260] mL at 4 hours, p<0.001; 420 [330-523] vs 550 [500-650] mL at 24 hours, p<0.01). Transfusion requirements were lower in the tranexamic acid group compared with the control group (RBC 9% vs 28%), but the difference was not statistically significant. Treatment with tranexamic acid was not associated with a higher incidence of myocardial ischemia or other thrombotic events.
                Tranexamic acid reduces postoperative blood loss after coronary artery bypass grafting on the beating heart. Evaluation of transfusion requirements warrants further study. Twenty patients undergoing orthotopic heart transplantation were randomized preoperatively to receive either the serine proteinase inhibitor aprotinin in a low dose (560 mg; n = 10) or a placebo (control group, n = 10) at the time of transplantation. Blood loss 24 and 48 hours after transplantation was significantly lower in the group treated with aprotinin (i.e., 510 ml vs 820 ml, p less than 0.01, and 690 ml vs 1000 ml, p less than 0.03, respectively. Accordingly, the aprotinin group required significantly less transfused blood in the first 48 postoperative hours 0 to 250 ml versus 0 to 1000 ml (p less than 0.04). Seventy percent of the patients treated with aprotinin underwent transplantation without the need of nonautologous blood, compared with only 30% in the control group. Aprotinin reduces blood loss after cardiopulmonary bypass. Although there can be little doubt about the efficacy of aprotinin, its safety has been questioned recently and is still under investigation. Because of the potential for complications and the high cost, a selective strategy limiting drug delivery to patients with established postoperative bleeding will be more reasonable.
                In a prospective, randomized, double-blind trial we studied the effect of postoperative low-dose (2 million kallikrein inactivator units) aprotinin on blood loss and transfusion requirements in patients undergoing cardiopulmonary bypass. Fifty-seven patients were randomly assigned to two groups: aprotinin or placebo.
                The two groups were comparable in all demographic and surgical variables. Postoperative chest tube drainage was significantly less in the aprotinin group than in the placebo group (410 ml vs 696 ml, p < 0.01). The use of homologous blood products was significantly less in the aprotinin group than in the placebo group (0.4 +/- 0.5 unit vs 1.7 +/- 0.9 unit for packed red blood cells and 0.8 +/- 1.3 unit vs 2.3 +/- 1.6 unit for fresh frozen plasma).
                Our results suggest that postoperative aprotinin reduces blood loss and transfusion requirements and provides the opportunity to restrict its use selectively to patients with excessive postoperative bleeding. Cardiopulmonary bypass induces a systemic inflammatory response. Aprotinin, a nonspecific proteinase inhibitor is known to improve postoperative hemostasis and may modify the inflammatory reaction. This study evaluates the effects of low-dose aprotinin on inflammatory markers in patients scheduled for elective coronary artery bypass grafting.
                Patients were prospectively randomized into two groups: the control group (C) (n = 14) and the low-dose aprotinin group (A) (n = 15) with (2 x 10(6) KIU = 280 mg) aprotinin added to the pump prime. Cytokine response (interleukin-6, soluble TNF II receptor), terminal complement production (SC5b-9), and neutrophil activation (lactoferrin) were assessed up to 6 hours postoperatively. Clinical data and hemostatic factors including fibrinopeptide A, thrombin-antithrombin complex, D-dimer, and plasmin/alpha2-antiplasmin were investigated.
                In both study groups, a significant increase of all inflammatory markers was seen (IL-6, sTNF-IIR, SC5b-9, lactoferrin), p less than 0.001. Peak levels of complement production occurred after protamine administration, whereas cytokine increases were more pronounced postoperatively with marked elevation up to 6 hours. The markers did not differ significantly between groups throughout the study period (p > 0.05 at each time of determination). However, after protamine administration reduced fibrinolysis (D-dimer, plasmin/alpha2-antiplasmin) was detected in group A. Measurements for coagulation (fibrinopeptide A, thrombin-antithrombin complex) were not significantly influenced by aprotinin. The total amount of blood loss during the first 24 hours was significantly reduced in group A (p < 0.02).
                Low-dose aprotinin added to the pump prime does not inhibit the inflammatory response caused by cardiopulmonary bypass, but improves postoperative hemostasis. A potential effect of high-dose aprotinin on inflammatory markers remains to be elucidated. We conducted a prospective, multicenter, double-blinded, dose-ranging study to compare the risk/benefit ratio of large- and small-dose aprotinin with placebo after major orthopedic surgery. Fifty-eight patients were randomized into three groups: Large-Dose Aprotinin (4 M kallikrein inactivator unit [KIU] bolus before surgery followed by a continuous infusion of 1 M KIU/h until the end of surgery), Small-Dose Aprotinin (2 M KIU bolus plus 0.5 M KIU/h), and Placebo. Bleeding was measured and calculated. Bilateral ascending venography was systematically performed on the third postoperative day. Measured and calculated blood loss decreased in the Large-Dose Aprotinin group (calculated bleeding, whole blood, hematocrit 30%, median [range], 2,023 mL [633-4,113] as compared with placebo, 3,577 mL [1,670-21,758 mL]). The total number of homologous and autologous units was also significantly decreased in the Large-Dose Aprotinin group (2 U [0-5 U] as compared with placebo, 4 U [0-42 U]). No increase in deep vein thrombosis or pulmonary embolism was observed in the aprotinin groups. Large-dose aprotinin was safe and effective in dramatically reducing the measured and calculated bleeding and the amount of transfused red blood cell units after major orthopedic surgery.
                Large doses of aprotinin decrease blood loss and transfusion amount in major orthopedic surgery. Aprotinin has been used increasingly to reduce postoperative blood loss in open heart operations. Although it was reported as safe in earlier studies, the overall safety of prophylactic use has been questioned recently. Because of the potential for complications and the high cost, it will be reasonable to use aprotinin more selectively in the postoperative period.
                We prospectively studied the effect of postoperative low-dose aprotinin (2 million kallikrein inactivator units [280 mg]) on blood loss and transfusion requirements in patients undergoing cardiopulmonary bypass. Seventy-five patients were randomly assigned to three groups: prophylactic high-dose aprotinin (group 1), postoperative aprotinin (group 2), or a nonmedicated control group (group 3).
                The three groups were comparable in all demographic and operative variables. Postoperative chest tube drainage was significantly decreased in both aprotinin groups compared with that in the control group (295 mL in group 1 and 325 mL in group 2 versus 411 mL in group 3; p < 0.05). No significant difference was seen between the two aprotinin groups. The use of homologous blood products was significantly less in group 1 and group 2 than in group 3 (1.15 +/- 1.13 U and 1.35 +/- 1.30 U versus 2.55 +/- 1.09 U; p < 0.05).
                Our results suggest that postoperative aprotinin reduces blood loss and transfusion requirements comparably with prophylactic high-dose aprotinin. Thus, one can restrict its use to patients with excessive postoperative bleeding. Acute preoperative plateletpheresis (APP), cell salvage (CS) technique, and the use of aprotinin have been individually reported to be effective in reducing blood loss and blood component transfusion while improving hematological profiles in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). In this prospective randomized clinical study, the efficacy of these combined approaches on reducing blood loss and transfusion requirements was evaluated. Seventy patients undergoing primary coronary artery bypass grafting (CABG) were randomly divided into four groups: a control group (group I, n = 10) did not receive any of the previously mentioned approaches. An APP and CS group (group II, n = 20) experienced APP in which preoperative platelet-rich plasma was collected and reinfused after reversal of heparin, along with the cell salvage technique throughout surgery. The third group (group III, n = 22) received aprotinin in which 5,000,000 KIU Trasylol was applied during surgery, and a combination group (group IV, n = 18) was treated with all three approaches, i.e., APP, CS, and aprotinin. Compared with group I (896+/-278 mL), the postoperative total blood loss was significantly reduced in groups II, III, and IV (468+/-136, 388+/-122, 202+/-81 mL, respectively, p < 0.05). The requirements of packed red blood cells in the three approached groups (153+/-63, 105+/-178, 0+/-0 mL, respectively) also were reduced when compared with group I (343+/-118 mL, p < 0.05). In group I, six patients (6/10) received fresh-frozen plasma and three patients (3/10) received platelet transfusion, whereas no patients in the other three groups required fresh-frozen plasma and platelet. In conclusion, both plateletpheresis concomitant with cell salvage and aprotinin contribute to the improvement of postoperative hemostasis, and the combination of these two approaches could minimize postoperative blood loss and requirement. In total knee arthroplasty surgery, a blood conservation program is applied as a normal clinical practice to avoid allogenic transfusions. The objective of this study was to assess the effectiveness of tranexamic acid to reduce transfusions in total knee replacement even when a blood conservation program is applied.
                In a double-blind prospective study the patients scheduled for total knee arthroplasty were included in a well-established blood conservation program and then randomly assigned into two groups: In tranexamic acid group, 10 mg per kg ev bolus followed by 1 mg per kg per hour perfusion was administered, while in the control group, saline was given matching the protocol.
                Ninety-five patients were included (tranexamic acid group, 46; control group, 49). Thirty-three patients (34.7%) underwent preoperative procedures to reduce transfusions: presurgical autologous blood donation (12), recombinant erythropoietin (6), and elementary iron (15); postoperative drain for reinfusion was allocated in all the cases. Total blood loss on the fourth postoperative day was [mean (+/-SD)] 1744 (+/-804) mL in controls compared with 1301 (+/-621) mL in the tranexamic acid group (p < 0.05). Eleven units of blood were transfused (6 patients) in the control group versus one in the tranexamic acid group (p < 0.05). Only 2 patients (4%) in the tranexamic acid group received reinfusion of blood recovered by drains compared with 36 (73%) in the control group (p < 0.0001). No thromboembolic complications were detected.
                Tranexamic acid reduces blood losses and transfusion requirements even when a blood conservation program was used and it questions the usefulness of the postoperative reinfusion drains. We investigated the effect of intravenous tranexamic acid on hydroxyethyl starch (HES)-induced clot strength impairment after cardiac surgery. Patients were randomized to receive either 1 g tranexamic acid or the same volume of 0.9% saline after administration of 15 ml/kg of 6% HES (molecular weight, 200 kDa; degree of substitution, 0.5) in the immediate postoperative period. Modified thromboelastometry (ROTEM) using different activators [intrinsic ROTEM (InTEM), extrinsic ROTEM (ExTEM), fibrinogen ROTEM (FibTEM)] was carried out to evaluate clot formation and lysis. The clot formation time was prolonged, and the maximum clot firmness (MCF) and shear elastic modulus [G = 5000 x MCF / (100-MCF), dynes/cm(2)] decreased (all activators of ROTEM) after completion of HES (P < 0.001, two-factor analysis of variance). These abnormalities in blood coagulation persisted despite tranexamic acid. Maximal lysis (FibTEM), indicative of fibrinolytic activity, was increased after HES but no effect of tranexamic acid was observed. The cumulative chest tube drainage until the first postoperative morning was not different between the groups (1008 +/- 251 and 1081 +/- 654 ml, P = 0.698, respectively). We conclude that after cardiopulmonary bypass, HES-induced impairment in clot formation and strength, or increased fibrinolytic capacity, is not reversed by the administration of tranexamic acid. To define the effect of tranexamic acid use on perioperative and postoperative bleeding and blood transfusion requirements in women undergoing myomectomy.
                Among the patients that underwent myomectomy a total of 100 cases were included in the study. The patients (n=50) randomized to receive tranexamic acid were defined as Group I and those receiving saline were defined as Group II. Perioperative blood loss was calculated by measuring the volume in the suction apparatus and weighing the swabs. Postoperative blood loss was defined as the blood volume found in the subfascial suction drain. The two groups were compared for age, body mass index, basal hemoglobin and hematocrit, basal parameters of coagulation, the number and the volume of myomas removed, peri- and postoperative and total blood loss, duration of surgery and blood transfusion requirements.
                No significant difference was found between the two groups when compared age, body mass index, preoperative blood analysis, the number and volume of myomas removed. Statistically significant differences were found between the two groups when compared for postoperative and total blood loss and duration of surgery (p<0.01, p=0.03 and p=0.03, respectively). Perioperative blood loss and blood transfusion requirements were similar between the two groups (p=0.12 and p=0.25, respectively). There were no complications in either group.
                Our study is the first in the literature evaluating the effectiveness of tranexamic acid use on peri- and postoperative bleeding in gynecological surgery. No additional benefit of intravenous infusion of tranexamic acid was found. Tranexamic acid does not seem to be a useful adjunct in myomectomy if given according to the described protocol in this study. Risks and costs of allogeneic blood transfusions mandate strategies to reduce blood loss in surgery. The objective of this study was to assess the efficacy of antifibrinolytic treatment in reducing perioperative blood loss during total knee replacement.
                A double-blind, randomized and placebo-controlled clinical trial was carried out on 127 patients undergoing total knee replacement. Patients in the study group received tranexamic acid 10 mg kg(-1) i.v. just before the tourniquet was deflated and 3 h later, or epsilon-aminocaproic acid 100 mg kg(-1) before tourniquet deflation followed by continuous perfusion (1 g h(-1)) during 3 h. External perioperative blood loss was measured and total blood loss was calculated. The number of patients transfused and number of packed red cell (PRC) units transfused was recorded and possible postoperative thromboembolic complications were investigated.
                Total blood loss [mean (sd)] was 1099 ml (535) in the group that received antifibrinolytic agents and 1784 ml (660) in the control group (P<0.001). Five patients (7.5%) in the study group and 23 (38.3%) in the control group (P<0.001) received blood transfusions; the first group received a mean of 0.10 PRC unit per patient and the second, 0.58 (P<0.001). Mean reduction in haemoglobin levels (g dl(-1)) between preoperative and fifth day postoperative readings was 2.5 (0.9) in the study group and 3.4 (1.2) in the control group (P<0.001). Clinical assessment did not reveal any thromboembolic complications.
                Antifibrinolytic agents produce a significant decrease in blood loss in patients undergoing total knee replacement, reflected in a reduction in the number of blood transfusions required. We evaluated the blood conservation effects of tranexamic acid (TA) or aprotinin administered before and during cardiopulmonary bypass (CPB) in a prospective, randomized, double-blind study of 150 adult patients undergoing primary coronary artery bypass grafting surgery. Patients received either TA (2 g) or large-dose aprotinin (7 million KIU). Thirty additional untreated patients otherwise managed in a similar fashion were included from a recently completed study for comparison of outcomes. Demographic, medical, surgical, laboratory, mediastinal chest tube drainage (MCTD), transfusion, and outcome data were collected. Allogeneic blood product administration was tightly controlled. The demographic, medical, and surgical characteristics did not significantly differ between the two therapy groups. The median postoperative MCTD loss in the TA group did not significantly differ from that in the aprotinin-treated group (708 vs 600 mL). The percentage of patients that received no allogeneic blood products was 25% for the TA group and 27% for the aprotinin group (P = not significant). The median number of allogeneic blood products administered to the TA group (0 U) did not significantly differ from that administered to the aprotinin group (0 U). The percentage of patients with excessive MCTD (>1000 mL/24 h) did not significantly differ between groups (19% and 17%, respectively). In comparison, the control group had a significantly greater (P < 0.05) median MCTD (1020 mL), median allogeneic blood product exposure (4.5 U), and incidence of excessive MCTD (66%) and transfusion therapy (66%). These data help to support the use of pharmacologic methods to improve clinically relevant indicators of blood conservation for primary CPB procedures. Furthermore, the data show that TA is equivalent to aprotinin for blood conservation in patients at risk of excessive post-CPB bleeding and transfusion therapy. Implications: In a randomized, blind trial, we evaluated the effects of tranexamic acid or aprotinin on blood conservation after primary cardiopulmonary bypass surgery. Both drugs were equally effective in reducing blood loss, the incidence of transfusion, and the amount of blood products transfused compared with placebon. Aprotinin has been shown to have anti-inflammatory properties, but its effects on the inflammatory reaction to cardiopulmonary bypass remain controversial. This prospective, randomized, double-blind study evaluated the influence of aprotinin on various blood markers of inflammation during and after cardiopulmonary bypass.
                Sixty male patients underwent coronary artery bypass grafting. The patients were randomized into 3 groups: a placebo group, a second group receiving 2,000,000 KIU of aprotinin followed by an infusion of 500,000 KIU/h and 2,000,000 KIU in the pump prime, and a third group receiving half this dosage. Measurements of tumor necrosis factor, interleukin 6, interleukin 8, interleukin 10, endotoxin, histamine, complement factors, prekallikrein, and prostaglandin D(2) were obtained at baseline, 30 minutes after study drug loading, 10 minutes after the beginning of cardiopulmonary bypass, before the end of bypass, 4 hours after bypass, and on the first and second postoperative days.
                Aprotinin had no significant effect on any of these parameters. As expected, aprotinin reduced early blood loss in both treated groups.
                These results indicate that aprotinin at doses currently used to reduce blood loss has no significant influence on the systemic inflammatory response during moderate hypothermic cardiopulmonary bypass in human subjects, as assessed by the mediators measured in this study. Controlled study to assess the efficacy of aprotinin and Amicar in reducing blood loss during complex spinal fusions.
                To compare blood loss and the clotting profile with a thromboelastogram in patients with spinal deformities undergoing sequential anterior and posterior spinal fusions treated intraoperatively with either aprotinin or Amicar.
                Spinal fusion for correction of adult spinal deformities is associated with large blood losses despite the implementation of multiple factors to reduce this blood loss. The antifibrinolytics aprotinin and Amicar have both been shown to reduce blood loss in other surgical procedures with the potential for large blood loss. Hence, we compared their efficacy for reducing blood loss in complex spinal fusions.
                Sixty patients for elective sequential anteroposterior thoracolumbosacral fusions were randomly assigned to three groups: control, aprotinin, and Amicar. Patients were assessed for blood loss, transfusion requirements, postoperative complications, and coagulation profile using a thromboelastogram.
                The study demonstrated a significant reduction in total blood loss (aprotinin 3628 mL, Amicar 4056 mL, control 5181 mL) and transfusion requirements using the half-dose aprotinin regimen compared with Amicar or control. Aprotinin also preserved the thromboelastogram mean clot formation time, clot strength, and clotting index compared with Amicar or control.
                For complex spinal operations with large blood losses, the half-dose aprotinin regimen will reduce blood loss and the need for blood components and may have a role in reducing postoperative lung injury. The blood saving effect of aprotinin has been well documented in cardiac surgery. In thoracic surgery, very few recent studies, using rather high doses of aprotinin, have shown a similar result. In a randomized prospective trial, we have tested the influence of aprotinin using an ultra-low dose drug regime.
                Fifty-nine patients, mean age 58 +/- 13.25 years (mean +/- SD) undergoing general thoracic procedures were randomized into placebo (Group A) and treatment group (Group B). The group B (n = 29) received 500.000 IU of aprotinin after induction to anesthesia and a repeat dose immediately after chest closure. A detailed protocol with several laboratory parameters was recorded. Patients were transfused when perioperative Ht was less than 26%.
                The two groups were similar in terms of age, gender, diagnosis, pathology, co-morbidity and operations performed. The mean drainage of the first and second postoperative day in group B was significantly reduced (412.6 +/- 199.2 vs. 764.3 +/- 213.9 ml, p < 0.000, and 248.3 +/- 178.5 vs. 455.0 +/- 274.6, p < 0.001). Similarly, the need for fresh frozen plasma transfusion was lower in group B, p < 0.035. Both the operation time and the hospital stay were also less for group B but without reaching statistical significance (84.6 +/- 35.2 vs 101.2 +/- 52.45 min. and 5.8 +/- 1.6 vs 7.2 +/- 3.6 days respectively, p < 0.064). The overall transfusion rate did not differ significantly. No side effects of aprotinin were noted.
                The perioperative ultra-low dose aprotinin administration was associated with a reduction of total blood losses and blood product requirements. We therefore consider the use of aprotinin safe and effective in major thoracic surgery. Aprotinin is a non-specific inhibitor of serine proteases with hemostyptic and hemostatic properties. The effect covers suppression of fibrinolysis and support of the role of thrombocytes in coagulation. In a prospective randomized study we verified whether the application of aprotinin (Antilysin Spofa, Czech Republic) in the dosage effective in cardiosurgical patients reduces blood loss and the need for blood transfusion for orthopaedic patients.
                42 patients indicated to the primary THA were randomly selected into the study and control groups. Excluded were allergic patients and those who used aprotinin before.
                Administration of 2.10(6) KIU of aprotinin was started preoperatively and is continued in the course of the first hour of surgery. In the operated on patients we recorded prior to operation and in the first post-operative morning the level of hemoglobin in blood and hematocrit, the number of infusions and blood transfusion units administered in the course of the surgery and in the post-operative period until the first post-operative morning. We recorded blood loss in the period between the surgery and the first post-operative morning. Data acquired in the patients of the studied and control groups were compared by means of ANOVA test for repeated measuring and with the use of Mann-Whitney and chi 2-test, the level of significance p < or = 0.05. During the hospitalization we the patients were checked for symptoms of deep venous trombosis and tromboembolic or other adverse events.
                Hemoglobinemia and hematocrit in both groups significantly decreased after the operation (p < 0.0005), the differences between the studied and control groups were not significant. The number of administered blood units did not differ in the examined and control groups. The frequency of blood transfusions was postoperatively higher in the control group (59.1% as compared to 30%), however, the difference was not statistically significant (p = 0.059). Blood loss in the post-operative period was higher in the control group (p = 0.048). Patients from the control group got in total blood transfusion more frequently (p = 0.032). Differences in the total frequency of blood transfusion and in the amount of post-operative blood loss were statistically significant. In the course of hospitalisation no signs of deep phlebothrombosis or thromboembolic condition were encountered in either group of patients. Complications were not recorded.
                Our results correspond with most of the published data. Blood loss of the operated on patients who were administered prior to and at the beginning of the operation in total 2.10(6) KIU of aprotinin (Antilysin Spofa) in infusion was on average by 33% less in the post-operative period and in the whole peropetive period they required less frequently blood transfusion (40% vs 73%).
                Infusion of aprotinin (Antilysin Spofa) in the dosage of the order of 106 KIU significantly reduces post-operative blood loss and frequency of transfusion in the peroperative period in patients undergoing THA. To assess the impact of systematic use of aprotinin, 115 consecutive adults undergoing cardiac surgery were randomly allocated with a sealed envelope technique. Treated (T) patients (n = 58) received 2.10(6) Kallikrein Inactivating Units (KIU) before incision, 2.10(6) prior to bypass, and 5.10(5) KIU.hr-1 for 5 hrs, whereas control (C) cases (n = 57) received nothing. Surgeons, perfusionists, ICU and ward physicians were blinded. Postoperative blood loss decreased from 1198 ml (C) to 698 ml (T) (p less than 0.001). Total transfusional needs were 7.25 (C) and 4.9 (T) units (p less than 0.01), where from 65% were autologous in group T, versus 51% in group C (p less than 0.02). Total homologous exposure decreased from 4.5 (C) to 2.7 (T) units on the average, from 3 to 1 units as a median (p less than 0.01). Multiple Stepwise Regression Analysis showed treatment as the most important variable influencing postoperative blood loss, but duration and type of procedures were more important to explain transfusion needs. Both groups were comparable for other pre- and intra-operative variables. For coronary operations (n = 75), aprotinin showed the strongest negative association with blood loss, the number of arterial conduits being the second influencing variable. No evidence was found for increased early graft thrombosis. The average hospital bill was 9% lower in the treated group, an unexplained finding needing independent confirmation. Of 22 patients undergoing repeat open-heart surgery through a previous median sternotomy wound 11 were randomised to receive the serine proteinase inhibitor aprotinin in high dosage (about 700 mg intravenously from the start of anaesthesia to the end of operation, depending on the length of the surgical procedure). Their mean blood loss was 286 ml compared with 1509 ml in the 11 control patients (p less than 0.001), and mean haemoglobin losses were 8.3 g and 78 g, respectively (p less than 0.001). Blood transfusion requirements were eightfold higher in the control group than in the aprotinin group, 7 of whom received only the single unit of their own blood taken before cardiopulmonary bypass. Aprotinin (APR) reduces postoperative blood loss but may induce thrombosis. Dipyridamole (DIP) limits platelet aggregation and may reduce the thrombotic complications associated with APR.
                To evaluate the safety and effectiveness of combined APR and DIP, we undertook a prospective randomized trial in patients undergoing cardiac operations. Patients were stratified according to risk for bleeding (low or high), and received either DIP with placebo (DIP group; n = 59) or DIP with APR (DIP + APR group; n = 56). Blood samples were obtained for the measurement of hematologic and biochemical parameters. Blood loss and transfusion requirements were documented postoperatively.
                Postoperative blood loss and transfusion requirements were significantly lower in the DIP + APR group at 6, 12, and 24 hours after bypass (p < 0.01). No significant differences were found between groups in the incidence of perioperative mortality (DIP, 0%; DIP + APR, 3%), myocardial infarction (DIP, 0%; DIP + APR, 3%), stroke (DIP, 1%; DIP + APR, 1%), or potential thrombotic events (death, myocardial infarction, and stroke: DIP, 2%; DIP + APR, 5%). In addition, these rates did not differ from those of nonparticipating matched control patients.
                Administration of both drugs simultaneously was more effective than DIP alone in reducing postoperative blood loss. A platelet inhibitor may be required to reduce the thrombotic complications associated with APR. Further studies evaluating graft patency and perioperative ischemia are necessary to confirm the potential benefits of the combination of a platelet inhibitor and APR. Ninety-seven patients undergoing elective liver resection through a subcostal incision were assigned to large-dose aprotinin treatment or placebo in a double-blind, prospective, randomized fashion. Randomization was stratified by diagnosis: (a) cancer in cirrhosis, (b) cancer in healthy liver, and (c) benign tumor in healthy liver. Intraoperative blood loss, percentage of transfused patients, and total transfusion requirement per group were significantly lower in the aprotinin group than in the placebo group (1217 +/- 966 mL vs 1653 +/- 1221 mL, P = 0.048; 17% vs 39%, P = 0.02; 30 vs 77 red blood cell packs, P = 0.015, respectively). Assessment of hematological markers (a) prior to surgery, (b) at the end of surgery, and (c) 24 h after surgery showed an identical intraoperative increase in thrombin-antithrombin III complexes in patients of both groups (P = 0.86), which indicates a similar activation of coagulation. Intraoperative hyperfibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group (P = 0.0002 and P = 0.004 for D-dimers and fibrinogen, respectively). No adverse drug effects were detected (circulatory disturbances, deep venous thrombosis, increase in serum creatinine). These results suggest that aprotinin significantly reduces blood loss and transfusion requirement in patients undergoing elective liver resection through a subcostal incision. To investigate an effect of tranexamic acid on blood loss associated with total knee arthroplasty (TKA).
                From June 2005 to June 2006, 102 patients (43 males, 59 females; aged 59-77 years, averaged 68 years) underwent TKA. Of the 102 patients, 59 had osteoarthritis, 23 had rheumatoid arthritis, and 20 had traumatic arthritis. The illness course ranged from 2 to 12 years. They were randomized divided into Group A and Group B of 51 patients each. The patients in Group A received tranexamic acid, and the patients in Group B received an equal volume of normal saline. In Group A, 1 g of tranexamic acid dissolved in 250 ml of normal saline was intravenously infused before deflation of the tourniquet; another intravenous administration of the same drug of the same dosage was given 3 hours later. In Group B, only 250 ml of normal saline was infused intravenously. The amounts of blood loss and blood transfusion during operation and after operation in all the 102 patients were recorded. They were also observed for whether they had deep vein thrombosis. D-dimeride, fibrinogen, prothrombin time, and activated partial thromboplastin time were also examined before operation, during operation (deflation of the tourniquet), and 3 hours after operation.
                The blood loss was 256 +/- 149 ml in Group A and 306 +/- 214 ml in Group B during operation; there was no significant difference between the two groups (P > 0.05). The postoperative drainage volume was 478 +/- 172 ml in Group A and 814 +/- 156 ml in Group B, and the total blood loss was 559 +/- 159 ml in Group A and 1208 +/- 243 ml in Group B; there were significant differences between the two groups (P < 0.05). The averaged amount of blood transfusion was 556 +/- 174 ml in Group A and 1024 +/- 278 ml in Group B; there was a significant difference between the two groups (P < 0. 05). The postoperative hemoglobin concentration was higher in Group A than that in Group B (1.0-1.1 g/dL vs. 0.6-0.8 g/dL). The postoperative follow-up for 6-12 months revealed that no deep vein thrombosis was found in both lower limbs of the patients by the color Doppler ultrasonography. The level of D-dimeride was significantly higher 3 hours after operation than before operation (0.92 +/- 0.56 mg/L vs. 0.35 +/- 0.13 mg/L in Group A; 1.32 +/- 0.79 mg/L vs. 0.37 +/- 0.21 mg/L in Group B) (P < 0.05). The D-dimeride level 3 hours after operation was significantly higher in Group B than in Group A (P < 0.05). There were no significant differences in the levels of fibrinogen, prothrombin time,.and activated partial thromboplastin time between the two groups (P > 0.05).
                During and after the TKA operation, a short-term use of tranexamic acid can significantly decrease blood loss and blood transfusion with no increasing risk for venous thrombosis. The efficacy of prophylactic epsilon-aminocaproic acid and tranexamic acid to reduce transfusions after primary myocardial revascularization was evaluated in a teaching hospital context.
                Patients (n = 134) received either epsilon-aminocaproic acid (15-g bolus + infusion of 1 g/h), high-dose tranexamic acid (10-g bolus + placebo infusion), or normal saline solution in a double-blind fashion. Anticoagulation and conduct of cardiopulmonary bypass were standardized.
                Tranexamic acid and epsilon-aminocaproic acid produced a significant reduction in postoperative blood loss compared with placebo (median loss, 438 mL, 538 mL, and 700 mL, respectively). Transfusion of red cells was similar in all three groups. Nonetheless, the percentage of patients receiving hemostatic blood products was significantly decreased in the epsilon-aminocaproic acid group compared with the placebo group (20% versus 43%; p = 0.03). Both tranexamic acid and epsilon-aminocaproic acid significantly decreased total exposure to allogeneic blood products compared with placebo (p = 0.01 and p = 0.05, respectively), and this reduction was clinically important (median exposure, 2, 2, and 7.5 units, respectively). Fibrinolysis was inhibited significantly in both treatment groups.
                We conclude that either high-dose tranexamic acid or epsilon-aminocaproic acid effectively reduces transfusions in patients undergoing primary, elective myocardial revascularization. We evaluated the effect of tranexamic acid on blood loss in patients undergoing elective cardiopulmonary bypass for coronary artery bypass surgery.
                We randomly assigned 7 of 14 patients to a group receiving 50 mg/kg tranexamic acid before skin incision and after the start of cardiopulmonary bypass and the other 7 as controls.
                Intraoperative and postoperative blood loss was significantly (p = 0.025) reduced in the tranexamic acid group. A similar decrease in platelet count was observed during cardiopulmonary bypass in both groups. Antithrombin III was significantly (p = 0.013) decreased in both groups during cardiopulmonary bypass. Antithrombin III and thrombin-antithrombin III complexes were significantly (p = 0.001) increased after protamine administration. A significant (p = 0.010) decrease in alpha 2-plasmin inhibitor was noted at 5 and 60 minutes after the start of cardiopulmonary bypass in the tranexamic acid group. alpha 2-plasmin inhibitor-plasmin complexes were significantly (p = 0.001) increased after the start of cardiopulmonary bypass in both groups and were significantly (p = 0.012) decreased after protamine administration. alpha 2-plasmin inhibitor-plasmin complexes in the tranexamic acid group were significantly (p = 0.030) lower than in controls 60 minutes after the start of cardiopulmonary bypass, just prior to the end of cardiopulmonary bypass, and after protamine administration.
                These findings showed that tranexamic acid administration effectively prevented perioperative blood loss without thromboembolic complications and that tranexamic acid during cardiopulmonary bypass coordinates the anticoagulative effect of heparin and the antifibrinolytic effect of tranexamic acid. High-dose aprotinin reduces transfusion requirements in patients undergoing coronary artery bypass grafting, but the safety and effectiveness of smaller doses is unclear. Furthermore, patient selection criteria for optimal use of the drug are not well defined.
                Seven hundred and four first-time coronary artery bypass grafting patients were randomized to receive one of three doses of aprotinin (high, low, and pump-prime-only) or placebo. The patients were stratified as to risk of excessive bleeding.
                All three aprotinin doses were highly effective in reducing bleeding and transfusion requirements. Consistent efficacy was not, however, demonstrated in the subgroup of patients at low risk for bleeding. There were no differences in mortality or the incidences of renal failure, strokes, or definite myocardial infarctions between the groups, although the pump-prime-only dose was associated with a small increase in definite, probable, or possible myocardial infarctions (p = 0.045).
                Low-dose and pump-prime-only aprotinin regimens provide reductions in bleeding and transfusion requirements that are similar to those of high-dose regimens. Although safe, aprotinin is not routinely indicated for the first-time coronary artery bypass grafting patient who is at low risk for postoperative bleeding. The pump-prime-only dose is not currently recommended because of a possible association with more frequent myocardial infarctions. Aprotinin reduces blood loss in many orthopedic procedures. In posterior lumbar spine fusion, blood loss results primarily from large vein bleeding and also occurs after the wound is closed. Seventy-two patients undergoing posterior lumbar spine fusion were randomly assigned to large-dose aprotinin therapy or placebo. All patients donated three units of packed red blood cells (RBCs) preoperatively. Postoperative blood loss was harvested from the surgical wound in patients undergoing two- and/or three-level fusion for reinfusion. The target hematocrit for RBC transfusion was 26% if tolerated. Total (intraoperative and 24 h postoperative) blood loss, transfusion requirements, and percentage of transfused patients per treatment group were significantly smaller in the aprotinin group than in the placebo group (1935 +/- 873 vs 2809 +/- 973 mL per patient [P = 0.007]; 42 vs 95 packed RBCs per group [P = 0.001]; 40% vs 81% per group [P = 0.02]). Hematological assessments showed an identically significant (a) intraoperative increase in both thrombin-antithrombin III complexes (TAT) and in activated factor XII (XIIa) and (b) decrease in activated factor VII (VIIa), indicating a similar significant effect on coagulation in patients of both groups (P = 0.9 for intergroup comparisons of postoperative VIIa, XIIa, and TAT). Intraoperative activation of fibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group (P < 0.0001 for intergroup comparison of postoperative D-dimer levels). No adverse drug effects (circulatory disturbances, deep venous thrombosis, alteration of serum creatinine) were detected. Although administered intraoperatively, aprotinin treatment dramatically reduced intraoperative and 24-h postoperative blood loss and autologous transfusion requirements but did not change homologous transfusion in posterior lumbar spine fusion.
                In our study, aprotinin therapy significantly decreased autologous, but not homologous, transfusion requirements in posterior lumbar spine fusion. We investigated the effects of tranexamic acid in 40 patients who had received cementless total hip arthroplasty (THA) in a prospective, randomized study. In 20 patients, 1000 mg of whole-body tranexamic acid was administered intravenously 5 min before the operation started. The other 20 patients served as a control group and were operated on without tranexamic acid. Perioperative blood loss was similar in the tranexamic acid group and in the control group. Postoperative blood loss of the tranexamic acid group was significantly less than that of the control group at 2, 4, 6, 8, 10, and 12 h. Regarding time-related changes of postoperative blood loss, significant reduction was observed during the first 2 h after surgery in the tranexamic acid group ( P<0.001). After the first 2 h, there was no significant difference between the tranexamic acid group and the control group. Preoperative administration of tranexamic acid decreased postoperative blood loss until 12 h and total bleeding in cementless THA by reduction of blood loss during the first 2 h after surgery. To assess the relative efficacy of a "low-dose" aprotinin regimen and tranexamic acid on blood loss and homologous blood usage in patients undergoing primary cardiac surgery.
                The trial was prospective, randomized, and controlled.
                A single center study in a regional cardiothoracic unit in the UK.
                75 Patients, age 18 years or over, who were scheduled for routine primary cardiac surgery.
                The patients were randomly allocated to receive neither drug nor placebo, a total of 5 g of tranexamic acid, or a total of 2 x 10(6) kallikrein inhibitory units of aprotinin in the perioperative period.
                The volume of blood loss and blood replacement were measured in the operative and postoperative periods. Hemoglobin concentration, platelet count, and white cell counts were determined preoperatively and at 24 hours postoperatively. Patients receiving tranexamic acid or aprotinin showed a significant reduction in postoperative blood loss (median[interquartile range] 375 mL [252 to 542] and 230 mL [137 to 547]), respectively, compared with the control group (615 mL [430 to 861]). Blood usage was also reduced in patients in both the tranexamic acid group (600 mL [415 to 800]) and the aprotinin-treated group (420 mL [350 to 887]) compared with the control group (1,050 mL [0 to 1,337]). There was no significant difference in blood loss or homologous blood use between patients treated with tranexamic acid or aprotinin.
                Tranexamic acid is as effective as low-dose aprotinin in the reduction of postoperative blood loss and homologous blood transfusion in patients undergoing primary cardiac surgery. Aprotinin is a serine protease inhibitor that reduces blood loss and transfusion requirements when administered prophylactically to cardiac surgical patients. To examine the safety and dose-related efficacy of aprotinin, a prospective, multicenter, placebo-controlled trial was conducted in patients undergoing repeat coronary artery bypass graft (CABG) surgery.
                Two hundred eighty-seven patients were randomly assigned to receive either high-dose aprotinin, low-dose aprotinin, pump-prime-only aprotinin, or placebo. Drug efficacy was determined by the reduction in donor-blood transfusion up to postoperative day 12 and in postoperative thoracic-drainage volume. The percentage of patients requiring donor-red-blood-cell (RBC) transfusions in the high- and low-dose aprotinin groups was reduced compared with the pump-prime-only and placebo groups (high-dose aprotinin, 54%; low-dose aprotinin, 46%; pump-prime only, 72%; and placebo, 75%; overall P = .001). The number of units of donor RBCs transfused was significantly lower in the aprotinin-treated patients compared with placebo (high-dose aprotinin, 1.6 +/- 0.2 U; low-dose aprotinin, 1.6 +/- 0.3 U; pump-prime-only, 2.5 +/- 0.3 U; and placebo, 3.4 +/- 0.5 U; P = .0001). There was also a significant difference in total blood-product exposures among treatment groups (high-dose aprotinin, 2.2 +/- 0.4 U; low-dose aprotinin, 3.4 +/- 0.9 U; pump-prime-only, 5.1 +/- 0.9 U; placebo, 10.3 +/- 1.4 U). There were no differences among treatment groups for the incidence of perioperative myocardial infarction (MI).
                This study demonstrates that high- and low-dose aprotinin significantly reduces the requirement for donor-blood transfusion in repeat CABG patients without increasing the risk for perioperative MI. To evaluate the role of recombinant bovine aprotinin in reducing blood loss in coronary artery bypass graft surgery.
                An open-label, randomized, controlled study evaluating two dosage levels of recombinant aprotinin.
                Two acute care hospitals (Northwestern Memorial Hospital, Chicago, Ill., and the Scott & White Memorial Hospital, Temple, Texas).
                Patients undergoing primary and reoperation coronary artery bypass grafting were assigned to groups by means of a computer-generated table of random numbers. Treated (n = 48) and control (n = 36) patients did not differ significantly in age, sex, weight, number of grafts, or preoperative hemoglobin level.
                Recombinant aprotinin was given at two dosages. Dosage level 1 consisted of a bolus of 2 mg/kg intravenously immediately after the induction of anesthesia, 1 mg/kg added to each liter of the oxygenator prime, and 0.5 mg.kg-1.hr-1 infused continuously during operation. At dosage level 2, doses were doubled. Intraoperative monitoring of anti-factor Xa activity was performed, and additional doses of heparin were given on the basis of anti-factor Xa results.
                Preoperative and postoperative hemoglobin levels, amounts of autotransfusion device and chest tube drainage blood, and transfusions of allogeneic red blood cells. Adverse clinical events (alterations in renal function, graft thrombosis, myocardial infarction, and death) were recorded.
                Additional heparin was given to 48% patients in the aprotinin group and to 44% of control patients. Overall red blood cell loss (in milliliters, mean +/- standard deviation [SD]) was decreased with aprotinin at dosage level 1 for reoperations (1040 +/- 162 vs 1544 +/- 198, p < 0.01), and at dosage level 2 for all operations (primary operations, 886 +/- 362 vs 1333 +/- 618, p = 0.02; reoperations, 1191 +/- 560 vs 1815 +/- 1116, p = 0.2). Fewer patients in the aprotinin than in the control group had transfusions of donated blood (6/48 vs 12/36, p = 0.02) or reinfusion of chest tube drainage blood (12/48 vs 20/36, p < 0.01). Among patients receiving dosage level 1, there were no myocardial infarctions or deaths. At dosage level 2, one patient had profound bradycardia and died on day 12 and two patients had late graft closures. Two control patients had hypotension after bypass necessitating intraaortic balloon pumps, and one of these patients died. Postoperative increases in blood urea nitrogen and creatinine levels were small in both aprotinin and control groups. No hypersensitivity or other allergic reactions occurred.
                We conclude that, at the dosages given, recombinant bovine aprotinin decreases surgical blood loss and transfusion requirements in patients undergoing coronary artery bypass grafting, but its use requires appropriate monitoring of heparin use during bypass. Whether higher dosages of aprotinin increase the risk of graft thrombosis must be further assessed with a larger patient sample. In this prospective, randomised, double-blind study, we investigated the effect of epidural anaesthesia and an antifibrinolytic agent, Aprotinin (500,000 KIU in bolus before surgery and 500,000 KIU h(-1) in drip form during surgery), on intra and postoperative blood loss and transfusion requirements in total hip arthroplasty. Sixty patients were allocated randomly to four groups (A: epidural + general anesthesia + Aprotinin, B: epidural + general anesthesia + placebo (equal volume), C: general anaesthesia + Aprotinin, D: general anaesthesia + placebo). Postoperative analgesia: epidural analgesia in groups A and B, systemic analgesia with opiates in groups C and D. Blood loss during surgery was monitored and salvaged with the Compact-A Dideco, and postoperative blood loss with the BT 797 Recovery Dideco for the first 24 hours. Perioperative blood loss, frequency and quantity of transfusions were significantly higher in group D (p<0.0001). Total blood loss was reduced by 31.3% by epidural anaesthesia, 20.4% by Aprotinin and 51.4% using a combination of the two techniques. During liver transplantation (LT), profound activation of the fibrinolytic system can contribute significantly to perioperative bleeding. Prophylactic administration of antifibrinolytic agents has been shown to reduce blood loss and the need for allogeneic transfusion in these conditions.
                This prospective randomized trial included 51 cirrhotic patients undergoing LT. Patients were randomly assigned to receive either 280 mg of aprotinin (AP) followed by 70 mg per hour or 40 mg per kg tranexamic acid (TA) followed by 40 mg per kg per hour, administered from the end of the anhepatic phase until 2 hours after reperfusion of the graft, and the effects on blood loss and red blood cell (RBC) transfusion requirements were compared. Transfusion policy was standardized in all patients. In addition, the biological effects of the two drugs, as assessed by coagulation and fibrinolytic markers obtained during surgery, were evaluated in a subgroup of patients from each treatment group and compared with an historical control group that did not receive antifibrinolytic drugs.
                There was no significant difference between the two groups in perioperative blood losses (AP, 6200 [4620-8735] mL; TA, 5945 [4495-8527] mL; median [range]) or in RBC transfusions requirements (AP, 9 [6.75-15.25] units; TA, 10 [6.5-13.5] units). Inhibition of fibrinolysis was observed with both drugs compared with the control group. Coagulation appeared to be activated more with AP, however, whereas fibrinolysis was inhibited more by TA.
                Blood losses and RBC transfusion requirements were comparable regardless of the drug administered. TA may be as valuable as AP for controlling fibrinolysis in LT. Patients on cardiopulmonary bypass (CPB) have an increased susceptibility to postoperative bleeding. Previous reports using desmopressin acetate (DDAVP) for the prevention of postoperative bleeding have given contradictory results, whereas the protease inhibitor aprotinin has been shown to reduce blood loss after this type of surgery. This randomized study was performed to assess the efficacy of DDAVP versus aprotinin in the prevention of bleeding after CPB.
                One hundred nine of 122 eligible patients were randomized to four different groups: Group A (n = 28) received aprotinin starting with a bolus of 2 x 10(6) KIU followed by a continuous infusion of 0.5 x 10(6) KIU/h until the end of surgery; group B (n = 25) received of DDAVP 0.3 micrograms/kg i.v. on completion of CPB; group C (n = 28) received two doses of DDAVP, the first as in group B and an additional dose 6 hours after surgery; group D (n = 28) received no treatment. There was a marked reduction of postoperative blood loss either at 12 hours (P < .01) or 72 hours (P < .02) in the aprotinin group compared with all other groups, whereas no significant effect was observed in either of the two DDAVP regimens. A significant reduction in the amount of blood used was observed only in the aprotinin group (P < .01). Of the plasma fibrinolytic components assayed, there was a significant reduction of the fibrin degradation product generation in the aprotinin group (P < .001), whereas a significant systemic hyperfibrinolysis was observed in both DDAVP-treated groups and the control group. No side effects related to the study drugs were observed in any patient.
                Aprotinin inhibited fibrinolysis; this correlated with a significant reduction of postoperative blood loss and need for blood replacement after CPB. Neither one nor two doses of DDAVP had a beneficial effect. Aprotinin offers a better alternative than DDAVP in the prevention of bleeding after CPB. This prospective, double-blind, randomized trial assessed the effectiveness of high-dose tranexamic acid given in the preoperative period on blood loss in patients undergoing cardiopulmonary bypass. One hundred fifty patients scheduled to undergo cardiac operations with cardiopulmonary bypass were randomized into three groups of equal size. The first group received 10 gm of tranexamic acid intravenously over 20 minutes before sternotomy and a placebo infusion over 5 hours. The second group received 10 gm of tranexamic acid over 20 minutes and then another 10 gm infused intravenously over 5 hours. The control group received a placebo bolus and a placebo infusion over 5 hours (0.9% normal saline solution). The blood loss after the operation was measured at 6 hours and 24 hours. The homologous blood and blood products given during and up to 48 hours after operation were recorded. Eighteen percent of the control group patients shed more than 750 ml blood in 6 hours compared with only 2% in both tranexamic acid groups. Patients who shed more than 750 ml blood required 93% more red blood cell transfusions than patients without excessive bleeding. Tranexamic acid (10 gm) given intravenously in the period before cardiopulmonary bypass reduced blood loss over 6 hours by 50% and over 24 hours by 35%. Continued tranexamic acid infusion (10 gm over 5 hours) did not reduce bleeding further. There was no difference in the coagulation profile before operation between patients with and without excessive bleeding. However, coagulation tests done in the postoperative period indicated ongoing fibrinolysis and platelet dysfunction in patients with excessive bleeding. Tranexamic acid reduces postoperative bleeding after coronary artery bypass grafting. We evaluated the effects of a single dose of tranexamic acid given immediately before cardiopulmonary bypass (CPB) in patients treated with aspirin until the day before surgery. The study was a prospective, randomized, double-blinded, placebo-controlled, parallel-group trial. Eighty patients were included and divided into two groups: one group received tranexamic acid 30 mg/kg, and one group received placebo (0.9% NaCl) as a bolus injection before CPB. Postoperative blood loss was recorded for 16 h. Transfusions of blood products were recorded for the whole hospital stay. Transfusions of packed red cells were given when the hematocrit value was less than 20% during CPB and less than 25% after surgery. The patients in the tranexamic acid group had significantly less postoperative bleeding compared with the patients in the placebo group (mean [SD]) (475 [274] mL versus 713 [243] mL; P < 0.001). An effective inhibition of fibrinolysis was found in patients receiving tranexamic acid. Tranexamic acid reduces postoperative bleeding in coronary artery bypass grafting patients treated with aspirin until the day before surgery.
                Continuation of aspirin medication until the day before coronary artery bypass grafting may increase postoperative bleeding. The administration of a single dose of tranexamic acid (30 mg/kg) immediately before cardiopulmonary bypass significantly reduced postoperative bleeding and inhibited fibrinolysis in these patients. To examine the feasibility of a real "blood transfusion"-free hepatectomy in a large group of patients with liver tumors.
                Bleeding control and blood transfusion remains problematic in liver resection. A real "blood transfusion"-free hepatectomy in a large group of patients has rarely been reported. The impact of tranexamic acid (TA), an antifibrinolytic agent, on blood transfusion in liver resection is unknown.
                A prospective double-blind randomized trial was performed on elective liver tumor resections. In group A, TA 500 mg was intravenously administered just before operation followed by 250 mg, every 6 hours, for 3 days. In group B, only placebo was given. The patients' background, blood transfusion rates, and early postoperative results in the 2 groups were compared. Factors that influenced blood requirement were analyzed.
                There were 108 hepatectomies in group A and 106 hepatectomies in group B. The patients' backgrounds, operative procedures, and hepatectomy extent did not significantly differ between the 2 groups. Although the differences of the operative morbidity and postoperative stay were not significant, a significantly lower amount of operative blood loss, lower blood transfusion rate, shorter operative time, and lower hospital costs were found in group A patients. No patient in group A received blood transfusion. No hospital mortality occurred in either group. Tumor size and use of TA were independent factors that influenced blood transfusion.
                Perioperative parenteral use of TA reduced the amount of operative blood loss and the need for blood transfusion in elective liver tumor resection. A real "blood transfusion"-free hepatectomy may be feasible with the assistance of parenteral TA. The prophylactic use of aprotinin has recently been reported to be associated with a significant decrease in blood loss in patients undergoing cardiopulmonary bypass procedures. One of the primary effects of aprotinin is prevention of plasmin degradation of platelet function. Because aprotinin is commercially unavailable in the United States at this time, we evaluated epsilon-aminocaproic acid with respect to decreased perioperative blood loss. We prospectively randomized 40 patients undergoing first-time coronary artery bypass grafting without prior sternotomy into two groups: one group (n = 21) received prophylactic and preincision epsilon-aminocaproic acid and the other (n = 19) received a placebo. No significant differences existed between patient groups with respect to age, body surface area, cardiopulmonary bypass time, and aortic crossclamp time. Cumulative blood loss at 4, 8, 12, and 24 hours after chest closure was significantly less in the epsilon-aminocaproic acid group (426 +/- 242 ml versus 634 +/- 224 ml, p = 0.002, at 12 hours). Only one patient receiving epsilon-aminocaproic acid was given blood or blood components compared to five patients in the placebo group (p < 0.02). D-dimers and fibrin split products were significantly less prevalent in the epsilon-aminocaproic acid group (at 4 hours: 0/20 versus 7/16, p < 0.002 and 5/20 versus 12/19, p < 0.05, respectively). None of the patients had a perioperative myocardial infarction or cerebrovascular accident. The prophylactic administration of epsilon-aminocaproic acid results in a significant decrease in blood loss in patients undergoing first-time coronary artery bypass grafting, and blood transfusion requirements are significantly less. It may be important to administer epsilon-aminocaproic acid before skin incision to be optimally effective. Aprotinin, a proteinase inhibitor, has been reported to reduce blood loss significantly during cardiac surgery. The mechanisms of this effect remain unclear. We studied the effect of aprotinin on blood loss and transfusion requirement during total hip replacement. Potential mechanisms of action and side effects also were investigated.
                Forty patients scheduled for primary total hip replacement were randomized to receive, in double-blind fashion, either aprotinin given as a bolus of 2 x 10(6) kallikrein inactivator units (KIU) followed by an infusion of 5 x 10(5) KIU/h until the end of surgery or an equivalent volume of normal saline. Anesthesia and surgical techniques were standardized and systematic deep venous thrombosis prophylaxis was used. Peri- and postoperative blood loss and transfusion were measured. Fibrinolysis, coagulation pathways, and platelet function were assessed. Renal and hepatic function as well as the incidence of deep venous thrombosis also were assessed.
                Aprotinin reduced total blood loss from 1,943 +/- 700 ml to 1,446 +/- 514 ml (P < 0.05). This reduction of blood loss occurred during surgery (P < 0.05) and postoperatively (P < 0.001). Total amounts of blood transfused were 3.4 +/- 1.3 units/patient in the control group and 1.8 +/- 1.2 units/patient in the aprotinin group (P < 0.001). The activated partial thromboplastin time was significantly prolonged by aprotinin immediately after surgery, at 50.6 +/- 12.4 versus 32.3 +/- 4.6 s in control patients (P < 0.001), but results of the other coagulation tests were not different between the two groups. No side effects were observed in the aprotinin group. The incidence of deep venous thrombosis in the two groups was not significantly different.
                The use of high-dose aprotinin during total hip replacement results in a reduction in both blood loss and the amount of blood transfused. Aprotinin's mode of action, however, remains to be elucidated. Desmopressin-induced release of tissue plasminogen activator from endothelial cells may explain the absence of its hemostatic effect in patients undergoing cardiac surgery. Prior administration of the antifibrinolytic drug tranexamic acid might unmask such an effect, and combination therapy might thereby improve postoperative hemostasis.
                A double-blinded design randomly allocated 163 adult patients undergoing coronary revascularization, valve replacement, both procedures, or repair of atrial septal defect to four treatment groups: placebo, tranexamic acid given as 10 mg/kg over 30 minutes followed by 1 mg.kg-1.hr-1 for 12 hours initiated before skin incision, desmopressin given as 0.3 micrograms/kg over 20 minutes after protamine infusion, and both drugs. One surgeon performed all operations. Blood loss consisted of mediastinal tube drainage over 12 hours. Follow-up visits sought evidence of myocardial infarction and stroke. Desmopressin decreased neither the 12-hour blood loss nor the amount of homologous red cells transfused. Tranexamic acid alone significantly reduced 12-hour blood loss, by 30% (mean, 318 versus 453 ml; p less than 0.0001), without enhancement by desmopressin. Tranexamic acid also decreased the proportion of patients receiving homologous blood within 12 hours of operation (8% versus 21%, p = 0.024) and within 5 days of operation (22% versus 41%, p = 0.011).
                Desmopressin exerts no hemostatic effect, with or without prior administration of antifibrinolytic drug. Prophylactic tranexamic acid alone appears economical and safe in decreasing blood loss and transfusion requirement after cardiac surgery. To evaluate and compare hemostatic effects of tranexamic acid vs. aprotinin vs. placebo in off-pump coronary artery bypass (OPCAB) surgery and, in addition, to assess the safety of fibrinolytic inhibitors therapies.
                In a prospective, randomized, double-blind study finally 91 patients undergoing OPCAB were investigated (group A, n=32, tranexamic acid 1g before skin incision and continuously 200mg/h; group B, n=29, aprotinin 1,000,000IU before skin incision and 250,000IU/h; group C, n=30, placebo).
                Highly significant inter-group differences were found in cumulative blood loss within 4h (geometric means [95% confidence intervals]-group A: 89.3 [72.7, 109.8] mL, group B: 72.3 [49.2, 106.3] mL and group C: 192.3 [151.8, 243.5] mL) (P<0.001), within 8h (group A: 152.1 [120.7, 191.6] mL, group B: 130.3 [88.1, 192.8] mL and group C: 283.8 [226.0, 356.3] mL) (P=0.001), and within 24h postoperatively (group A: 410.3 [337.6, 498.6] mL, group B: 345.8 [256.0, 398.2] mL and group C: 619.8 [524.3, 732.8] mL) (P<0.001). At all time points, placebo group C was significantly distinct from the groups treated with fibrinolytic inhibitors (groups A and B). However, no differences between groups A and B were found. Both mean hemoglobin and hematocrit values 24h postoperatively were different between the groups (P=0.018 and P=0.077, respectively), acheiving the lowest value in group C. Number of re-transfuzed patients was highest in group C, but without statistical significance (either packed red blood cells, P=0.119 or fresh-frozen plasma, P=0.118). We observed one postoperative myocardial infarction in aprotinin treated group B and one temporary postoperative myocardial ischemia in placebo group C, no cerebrovascular or pulmonary embolism was noticed. Treated groups A and B did not demonstrate postoperative increase in mean levels of myocardial enzymes, compared with group C. Significantly higher mean values of D-dimer were found in group C 24h postoperatively (P<0.001).
                Both tranexamic acid and aprotinin seem to be similarly effective in the reduction of postoperative blood loss in OPCAB. Tranexamic acid appears to be cost-effective and safe alternative to aprotinin. Hemostatic drugs are widely thought to be unnecessary and potentially detrimental in off-pump coronary artery bypass graft surgery (OPCABG), despite well-established use in on-pump surgery. In a randomized, prospective OPCABG trial, we assessed efficacy and safety of aprotinin through a comprehensive assessment of graft patency and hematologic function.
                Sixty patients were randomly assigned to full-dose aprotinin or placebo. Heparin was titrated to a kaolin-based activated clotting time of greater than 300 seconds. Exclusionary criteria included creatinine greater than 2 mg/dL, conversion to on-pump CABG, and preoperative GPIIb/IIIa inhibition. Hematologic assessments were obtained preoperatively, at the end of surgery, and on days 1 and 3: mean platelet volume, thrombin generation (prothrombin fragment 1.2 assay), and aspirin resistance using a modified thrombelastography, whole blood aggregometry, 11-dehydro-thromboxane B2 levels, and flow cytometry. Thrombotic events were defined as postoperative myocardial infarction by electrocardiography or elevated troponin I, clinical stroke by examination and head computed tomography, and bypass graft failure by multichannel computed tomography angiography on day 5.
                Aprotinin was associated with a significant reduction in intraoperative and postoperative blood loss compared with placebo but had no effect on transfusion rates. Patients treated with aprotinin had significantly fewer thrombotic events (3% versus 23%, p < 0.05, Fisher's exact test) and less postoperative aspirin resistance (20% versus 46%, respectively, p < 0.05, Fisher's exact test). Postoperative prothrombin fragment 1.2 level was reduced by aprotinin use.
                Aprotinin reduced perioperative bleeding after OPCABG. Preserved aspirin sensitivity in the aprotinin group may explain the observed reduction in thrombotic events and might be related to the suppression of perioperative and transmyocardial thrombin formation. This study was designed to evaluate efficacy and tolerability of two different doses of aprotinin in patients receiving aspirin before undergoing coronary artery bypass grafting. Forty-two patients were randomized to receive either placebo (group I), or aprotinin in doses of 4,000,000 KIU (group II) or 6,000,000 KIU (group III). Drug efficacy was determined by measuring postoperative blood loss and transfusion of blood products. Both doses were effective in reducing blood loss and transfusion requirements. Blood loss through thoracotomy drainage was 450 +/- 224, 182 +/- 144, 142 +/- 98 ml, respectively, for control and treatment groups II and III (p = 0.0001). The numbers of patients with blood transfusions were seven (50%), two (17%) and two (17%) for group I and treatment groups II and III, respectively (p = 0.10). Tolerability was excellent and complications few and reversible. In conclusion, high and medium doses of aprotinin were well tolerated and reduced bleeding and transfusion requirements in patients submitted to coronary bypass surgery under the effects of aspirin. The safety of aprotinin, especially when used with profound hypothermic circulatory arrest, is still a matter of intense debate despite its presumed salutary effects on blood loss. Many investigators have reported toxic renal effects of high-dose aprotinin in such patients, but no prospective, randomized study has been conducted. To assess the potential detrimental effect of aprotinin on renal function and its putative reduction of blood loss, 50 patients undergoing thoracic aortic operations with the use of profound hypothermic circulatory arrest were randomly assigned to receive either low-dose aprotinin (1 x 10(6) kallikrein activation units) or placebo.
                The specific renal tubular markers beta-2-microglobulin and beta-N-acetyl-D-glucosaminidase, as well as serum creatinine and blood urea nitrogen, creatinine clearance, sodium excretion, and potassium excretion, were measured to evaluate renal function preoperatively, immediately after the procedure, and 24 hours and 48 hours later.
                No statistically significant difference was found in any measured renal parameter between the two groups (analysis of variance). Renal dysfunction, defined as an elevation of serum creatinine early postoperatively (> or = 1.5 times the preoperative value), occurred in two patients who received aprotinin and in one patient in the control group. Temporary dialysis (hemodialysis or continuous venovenous hemofiltration) was needed in two patients in the aprotinin group versus one in the control group. Furthermore, patients treated with aprotinin had significantly less total postoperative blood loss (718 +/- 340 ml vs 920 +/- 387 ml, p = 0.04). The aprotinin recipients also had a significantly lower transfusion requirement (p < 0.05).
                This controlled trial of low-dose aprotinin in patients undergoing thoracic aortic operations using profound hypothermic circulatory arrest demonstrated no detectable deleterious effects on renal function; moreover, the use of aprotinin was associated with significantly lower need for transfusion. A prospective randomized double-blind placebo-controlled study was undertaken to determine the efficacy and mechanism of action of two antifibrinolytic drugs aprotinin and epsilon aminocaproic acid (EACA) in reducing blood loss in primary unilateral total hip arthroplasty (THA). Aprotinin was administered as a bolus of 2 x 10(6) kallikrein inhibitor units (KIU) followed by 0.5 x 10(6) KIU h(-1) for 3 h, EACA was given as 10 g over 30 min followed by 5 g over 3 h. The median postoperative blood loss 24 h postoperatively was reduced from 450 mL in the placebo group to 180 mL for aprotinin (60% reduction, P < 0.001) and to 210 mL for EACA (53% reduction, P < 0.01). In this population, there was no reduction in the perioperative transfusion requirements. The mechanism of both drugs was independent of platelets as indicated by flow cytometric measurement of change of their expression of P-selectin, platelet-monocyte aggregates, V/Va and CD40 ligand. There were no thrombotic or infective complications and no adverse events were attributable to use of either drug. Infusion of either aprotinin or EACA at the doses described is a safe and effective means of reducing blood loss after THA. These therapies provide a means of reducing blood loss in THA patients. To compare the efficacy of aprotinin (APR) and tranexamic acid (TRA) in reducing blood loss and transfusion requirements after cardiac surgery under extracorporeal circulation (ECC).
                Randomized controlled trial.
                One hundred and four adults undergoing either coronary artery bypass grafting (CABG) (n = 55), or aortic valve replacement (AVR) (n = 49), allocated into three groups.
                a) APR group (23 CABG and 20 AVR) received aprotinin, 2 x 10(6) KIU (280 mg) after induction, followed by an infusion of 0.5 x 106 KIU.h-1 (70 mg.h-1) until chest closure, with a supplement to the oxygenator prime of 2 x 10(6) KIU; b) TRA group (22 CABG and 19 AVR) received tranexamic acid, 15 mg.kg-1 between the injection of heparin (400 IU.kg-1) and the beginning of ECC, 15 mg.kg-1 after protamin injection (1.3 mg/100 IU of heparin); c) CTR group (10 CABG and 10 AVR), the control group, was not treated with an antifibrinolytic agent. The amount of blood collected from the chest tube drainage was measured at admission to ICU, as well as 4, 8 and 18 h after the insertion of drains and at the time of their removal. Packed red cells where given when the haematocrit was under 20% during ECC, 25% at the end of surgery and 30% after extubation.
                The blood loss was lower in APR group (834 +/- 448 mL) than in TRA group (1015 +/- 409 mL) (P = 0.009), and in CTR group (1416 +/- 559 ML) (P = 0.004). The rates of transfused patients in groups APR, ATR and CTR were 35, 37 and 60% respectively and the numbers of units administered per patient were 0.8, 0.8 and 1.7 respectively. In AVR cases, APR and TRA had a similar efficacy. In CABG cases, only aprotinin decreased postoperative bleeding. However there was no difference between APR and TRA concerning the transfusion requirements. In CABG cases the ECC was of shorter duration and blood loss was 1127 +/- 540 mL vs 894 +/- 422 mL in AVR cases (P = 0.03).
                Both APR and TRA decrease blood loss. APR is more efficient after CABG than TRA as far as blood loss is concerned, whereas the transfusion requirements are similar. As APR is about 100 times more expensive and carries a risk for allergic reactions, its use in a high dose regimen is only recommended for reoperations, in patients treated with salicylates and in case of sepsis. Major orthopedic surgery can be associated with dramatic blood loss, thereby requiring high-volume homologous transfusions in patients unable to benefit from blood salvage techniques. The effect of aprotinin on blood loss and transfusion requirements during orthopedic surgery for either the resection of malignancies of the removal of infected hardware was prospectively studied.
                Twenty-three patients scheduled for orthopedic surgery of the hip, femur, or pelvis for sepsis or malignant tumors, all under general anesthesia, were randomly allocated to receive during operation, in a blinded manner, either aprotinin administered as a bolus of 1.106 kallikrein inactivation units (KIU) followed by an infusion of 5 x 10(5) KIU/h, or the equivalent volume of saline. The anesthesia and perioperative management, as well as the designated transfusion criteria, were standardized. The total blood loss of each patient was evaluated using intraoperative suction losses, sponge weights, and postoperative volumetric drainage. Homologous transfusion requirements were noted. Hemoglobin and hematocrit measures, as well as coagulation and fibrinolytic pathway explorations, were performed before and after surgery. Deep venous thrombosis prophylaxis was applied, and the incidence of this complication was assessed.
                Twelve patients received aprotinin. Aprotinin reduced the total blood loss from a median of 5,305 ml (range, 3,000-9,770 ml) to a median of 1,783 ml (range, 1,140-4,955 ml; P < 0.05). A blood loss reduction of 56% during surgery and 68% on discharge from the postanesthesia care unit was observed. Seven units (range, 4-16) of packed erythrocytes were transfused per patient in the placebo group, and 3 (range, 2-5) were transfused in the aprotinin group (P < 0.05). In the aprotinin group, platelet counts were higher, and postoperative prothrombin times and D. Dimer values were lower. The activated partial thromboplastin time values showed no significant difference between the two groups. No side effects were observed in the aprotinin group. A deep venous thrombosis developed in one patient in the placebo group.
                Aprotinin treatment during major orthopedic surgery significantly reduces both blood loss and consequent homologous blood transfusion requirements. The recruitment of leukocytes to vascular endothelium is controlled by adhesion events mediated through the beta2 integrins, whereas the response of extravasated leukocytes within the tissues is controlled through the beta1 integrins. Although cardiopulmonary bypass (CPB) has been shown to be associated with a systemic inflammatory response and elevated levels of beta2 integrins on leukocytes, its effect on the beta1 integrins is not known. This study investigated the effect of the protease inhibitor aprotinin on the expression of the beta1 and beta2 integrins on circulating leukocytes in patients undergoing CPB.
                Patients undergoing primary elective coronary artery bypass grafting were randomized into full-dose aprotinin or placebo groups. Blood samples were obtained at nine time points preoperatively, intraoperatively, and up to 6 days postoperatively. The surface expression of the beta1 integrins VLA-1, -3, -4, -5, and -6 and of the beta2 integrins CD11a/CD18, CD11b/CD18, and CD11c/CD18 was measured by flow cytometry on gated neutrophil and monocyte subpopulations in whole blood.
                Expression of the beta1 integrins was not significantly altered during the study period and, therefore, aprotinin had no effect on the expression of these molecules. Of the beta2 integrins, CD11b/CD18 expression was significantly increased on neutrophils at 15 minutes after onset of CPB in the placebo group (p < 0.01) but not in the aprotinin group.
                This study showed that expression of the beta1 integrins on neutrophils and monocytes did not alter during the first 6 days after CPB. Expression of the beta2 integrin CD11b/CD18 increased significantly on neutrophils during CPB in control patients but not in patients treated with full-dose aprotinin. To evaluate the efficacy of a 2 million KIU single dose of aprotinin on blood loss, transfusion requirements, and incidence of deep venous thrombosis (DVT) in patients undergoing total hip replacement surgery.
                Randomized study.
                Operating theater at an orthopedic hospital.
                40 adult patients scheduled for total hip replacement surgery.
                Patients were randomized to two groups. Group A (n = 20) received 2 million KIU of aprotinin over 20 minutes, Group C (n = 20), the control group, received placebo. Anesthesia and surgical technique were standardized. MEASUREMENTS AND MAIN-RESULTS: Intraoperative blood loss, postoperative blood loss, transfusion requirements (48 hr), hemoglobin, coagulation parameters, and platelet counts were assessed. On the seventh postoperative day, all patients in both groups underwent venography to ascertain the incidence of DVT. We found no significant difference in blood loss or transfusion requirements between the two groups. Intraoperative and postoperative blood losses, coagulation parameters, and incidence of DVT did not differ significantly between the two groups.
                A single 2 million KIU bolus dose of aprotinin does not reduce perioperative blood loss or transfusion requirements. Aprotinin therapy, when used in conjunction with other antithrombotic therapies, does not increase the incidence of DVT after major orthopedic surgery. To compare the efficacy of aprotinin and methylprednisolone in reducing cardiopulmonary bypass (CPB)-induced cytokine release, to evaluate the effect of myocardial cytokine release on systemic cytokine levels, and to determine the influence of cytokine release on perioperative and postoperative hemodynamics.
                Prospective, randomized clinical trial.
                University teaching hospital and clinics.
                Thirty patients undergoing elective coronary artery bypass graft surgery.
                Patients were randomly allocated into groups treated with aprotinin (n = 10) or methylprednisolone (n = 10) or into an untreated control group (n = 10). Aprotinin-treated patients received aprotinin as a high-dose regimen (6 x 10(6) KIU), and methylprednisolone-treated patients received methylprednisolone (30 mg/kg intravenously) before CPB.
                Patients were analyzed for hemodynamic changes and alveolar-arterial PO2 difference (AaDO2) until the first postoperative day. Plasma levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-6, and IL-8) were measured in peripheral arterial blood immediately before the induction of anesthesia, 5 minutes before CPB, 3 minutes after the start of CPB, 2 minutes after the release of the aortic cross-clamp, 1 hour after CPB, 6 hours after CPB, and 24 hours after CPB; and in coronary sinus blood immediately before CPB and 2 minutes after the release of the aortic cross-clamp. The hemodynamic parameters did not differ among the groups throughout the study. After CPB, AaDO2 significantly increased (p < 0.05) in all groups. A significant decrease in AaDO2 was observed in aprotinin-treated patients at 24 hours after CPB compared with the other groups (p < 0.05). TNF-alpha level from peripheral arterial blood significantly increased in control patients 1 hour after CPB (p < 0.01) and did not significantly increase in methylprednisolone-treated patients throughout the study. In all groups, IL-6 levels increased after the release of the aortic cross-clamp and reached peak values 6 hours after CPB. At 6 hours after CPB, the increase in IL-6 levels in methylprednisolone-treated patients was significantly less compared with levels measured in control patients and aprotinin-treated patients (p < 0.001). In control patients, IL-8 levels significantly increased 2 minutes after the release of the aortic cross-clamp (p < 0.05), and peak values were observed 1 hour after CPB (p < 0.01). IL-8 levels in control patients were significantly higher compared with patients treated with aprotinin and patients treated with methylprednisolone 1 hour after CPB (p < 0.05).
                This study showed that methylprednisolone suppresses TNF-alpha, IL-6, and IL-8 release; however, aprotinin attenuates IL-8 release alone. Methylprednisolone does not produce any additional positive hemodynamic and pulmonary effects. An improved postoperative AaDO2 was observed with the use of aprotinin.
                Copyright 2001 by W.B. Saunders Company To assess the efficacy and safety of the use of a high-dose regimen of aprotinin in routine cardiac operations, a placebo-controlled randomized double-blind study was conducted in 93 adult patients undergoing cardiopulmonary bypass. Aprotinin-treated patients (group A, n = 46) received 2 x 10(5) Kallikrein Inactivating Units (KIU) of aprotinin before incision, 2 x 10(6) KIU in the priming solution and 5 x 10(5) KIU/h during CPB. Control patients (group B, n = 47) received the same volume of normal saline. Mean postoperative blood loss in ml after six hours and in total until removal of thoracic drains decreased significantly from 752 and 1933 in controls, to 358 and 1051 in treated patients (p < 0.001). Mean total transfusion needs were 2.6 (A) and 4.8 (B) units per patient. Adverse events were evenly distributed between both groups and could not be attributed to aprotinin use. We, therefore, recommend the use of a high-dose regimen of aprotinin for routine cardiac operations despite its cost. We tested the efficacy and safety of aprotinin in 169 patients undergoing isolated reoperative myocardial revascularization. Patients were randomly assigned to high-dose aprotinin, low-dose aprotinin, or placebo treatment groups in a double-blind, placebo-controlled study. Treatment groups did not differ significantly with respect to age, sex, red cell mass, number of grafts, use of internal thoracic artery, or incidence of preoperative aspirin therapy. Patients treated with aprotinin had a significant reduction in postoperative chest tube drainage (720 +/- 753, 866 +/- 1,636, and 1,121 +/- 683 mL, respectively, for high-dose aprotinin, low-dose aprotinin, and placebo; p < 0.001). Transfusion requirements were reduced in aprotinin-treated patients (2.1 +/- 4.2, 4.8 +/- 11.8, and 4.1 +/- 6.2 units for high-dose, low-dose, and placebo, respectively; p < 0.001). A similar reduction in chest tube drainage and transfusion requirements was seen in patients using aspirin preoperatively. Q-wave myocardial infarctions were increased in the aprotinin subgroups (17.5%, 14.3%, and 8.9% for high-dose, low-dose, and placebo groups; not significant). Acute vein graft thrombosis was found in six of 12 vein grafts studied at postmortem examination in patients receiving aprotinin but not in any of five grafts in patients receiving placebo. We conclude that aprotinin is extremely effective in reducing bleeding and transfusion requirements and may increase the risk of graft thrombosis. In this prospective, randomized, double-blind study, we have investigated the effect of an antifibrinolytic agent, tranexamic acid (Cyklokapron), on blood loss and transfusion requirements associated with total knee arthroplasty. Twenty-nine patients were allocated randomly to receive either tranexamic acid 15 mg kg-1 or an equal volume of placebo a few minutes before a tourniquet was deflated. Blood loss during surgery, in the recovery room and on the surgical ward was recorded, together with the number of units of blood transfused in hospital. Mean blood loss during surgery was 428 (SD 254) ml in the tranexamic acid group (n = 15) compared with 415 (244) ml in the placebo group (n = 13). In the recovery room the tranexamic acid group lost 127 (95) ml and the placebo group 576 (245) ml (P < 0.001). On the ward the respective volumes were 293 (200) ml and 558 (293) ml (P < 0.01). Total blood loss was 847 (356) ml in the tranexamic acid group and 1549 (574) ml in the placebo group (P < 0.001). During the hospital stay the treatment group received 1.5 (1.3) units of blood compared with 3.3 (1.8) in the control group (P < 0.005). Two patients in the placebo group experienced a thrombotic complication compared with none in the treatment group. We conclude that tranexamic acid reduced perioperative blood loss and transfusion requirements associated with total knee arthroplasty. High dose aprotinin has been used in cardiac surgery (Royston 1987) to reduce post operative bleeding. A low dose aprotinin ie 2000000 KIU in the oxygenator prime, has been also proposed. OBJECTIVE. To evaluate postoperative losses and holomogous blood transfusions, in patients undergoing cardiac surgery treated with low and high dose aprotinin. METHODS AND MATERIALS. Ninety-nine patients, between January and May 1993, have randomized in 3 groups: A, high dose aprotinin; B, low dose aprotinin; C, control. All patients were treated with additional blood saving techniques routinely used in our center. Statistical analysis was performed by means of ANOVA and Tukey Kramer test. MAIN RESULTS. Five patients (3 in group A, 1 each in groups B and C) have been excluded during the trial. The groups resulted omogeneus and comparable. Total blood losses were 372 +/- 159 ml in group A, 401 +/- 178 ml in group B (difference are not significative); the 621 +/- 255 m1 in group C are highly significative. Patients transfused were 18.7% in group C, 10.34% in group A and 6.20% in group B. CONCLUSIONS. Effects of low dose aprotinin are comparable to high dose. Further advantages with low dose are reduction of collateral effects and intolerance phenomena and a better cost benefits ratio. Evidence exists that the serine protease inhibitor, aprotinin, when used in high dosage, can reduce the bleeding associated with cardiopulmonary bypass. This high dosage is particularly effective in patients at increased risk for bleeding. Less convincing information is available for regimens that use a lower dose and its place in routine cardiac surgery has not been fully resolved. Some studies have shown significant benefit from a single dose added to the cardio-pulmonary bypass prime and we re-examined this alternative. In a randomized, prospective, double-blinded study, we compared this single dose method with placebo in a low risk adults undergoing a first procedure. Benefit was considered established if a significant reduction in blood loss or the use of transfused blood products was seen. We found a significant reduction in red cell transfusion but no improvement in blood loss or blood component transfusion in the treated group. This included patients maintained on aspirin as well as those not receiving aspirin. Aspirin significantly increased blood loss in both control and treatment groups and the usage of blood products in the treatment group. Aprotinin in this low, single dosage was not confirmed as an effective means of improving hemostasis following CPB in routine cardiac surgery. Pharmacologic intervention to minimize postbypass bleeding and blood product transfusions has received increasing attention for both medical and economic reasons.
                Two hundred ten patients were entered into a double-blinded, prospective, randomized study to receive either 10 g of fibrinolytic inhibitor tranexamic acid before incision (n = 104) or 250 mL of placebo saline solution (n = 106). All subjects requiring cardiopulmonary bypass were deemed suitable, including those having first-time coronary bypass grafting, valve replacement, and reoperation.
                There were no statistically significant differences between the groups with respect to demographic or operative characteristics. The tranexamic acid group had a 48% reduction in 24-hour blood drainage (p < 0.001) and received 69% fewer total units of packed red blood cells, 83% fewer total units of plasma, and 75% fewer platelet transfusion units than controls. Only 13 of 104 tranexamic acid patients received blood products versus 33 of 106 controls (p < 0.001). The incidences of thrombotic complications, perioperative myocardial infarction, renal failure, and neurologic complications were not significantly different between the two groups. The tranexamic acid group had 0% mortality versus 1.9% for controls (not significant).
                Tranexamic acid is safe and effective in reducing blood loss and blood use in a wide variety of cardiac surgical patients. Total hip arthroplasty (THA) is associated with high intraoperative and postoperative blood loss. Antifibrinolytic drugs have been used to minimize the potential risks of bleeding and blood transfusion. Studies on the effect of tranexamic acid on decreasing blood loss in THA have revealed interesting results, but most have focused on cemented THA. Yet its benefits in THA, especially in cementless THA, have not been proved. We conducted a prospective double-blind randomized controlled study on 64 patients who were candidates for cementless THA under epidural anesthesia between 2006 and 2008. Patients were randomly assigned into study and control groups. Patients in both groups were well matched regarding preoperative characteristics. Five minutes preoperatively 32 patients of the study and control groups received 15 mg/kg tranexamic acid or normal saline intravenously respectively. Our findings showed a significantly smaller decrease in 6- and 24-hour postoperative hemoglobin levels, less intraoperative and postoperative bleeding, and less need for allogenic blood transfusion in the tranexamic acid group. Our results also revealed a higher mean of 6- and 24-hour hematocrit level and shorter hospital stay in the tranexamic acid group compared to the control group, which were not statistically meaningful. In our study no thromboembolic event was seen; except 1 patient in the control group. Our study showed that administering tranexamic acid before the start of cementless THA under epidural anesthesia can reduce intraoperative and postoperative bleeding as well as need for blood transfusion.
                Copyright 2010, SLACK Incorporated. Prophylactic administration of the antifibrinolytic drug tranexamic acid decreases bleeding and transfusions after cardiac operations. However, the best dose of tranexamic acid for this purpose remains unknown. This study explored the dose-response relationship of tranexamic acid for hemostatic efficacy after cardiac operation.
                In prospective, randomized, double-blinded fashion, 148 patients undergoing cardiac operation with extracorporeal circulation were divided into six groups: a placebo group and five groups receiving tranexamic acid in loading doses before incision (range 2.5 to 40 mg.kg-1) and one-tenth the loading dose hourly for 12 h. The mass of blood collected by chest tubes over 12 h represented blood loss. Allogeneic transfusions within 12 h and within 5 d of surgery were tallied.
                The six groups presented similar demographics. Patients receiving placebo had increased postoperative D-dimer concentration compared to groups receiving tranexamic acid. Patients receiving at least 10 mg.kg-1 tranexamic acid followed by 1 mg.kg-1.h-1 bled significantly less (365, 344, and 369 g.12 h-1, respectively, for those three groups) compared with patients who received placebo (552 g, P < 0.05). Tranexamic dose did not affect transfusions. Only initial hematocrit affected whether a patient received an allogeneic transfusion within 5 days of operation (odds ratio 2.08 for each 3% absolute decrease in hematocrit).
                Prophylactic tranexamic acid, 10 mg.kg-1 followed by 1 mg.kg-1.h-1, decreases bleeding after extracorporeal circulation. Larger doses do not provide additional hemostatic benefit. The hemostatic effect of tranexamic acid on the bleeding tendency and transfusion requirements in patients undergoing off-pump coronary artery bypass surgery was assessed in a prospective randomized double-blind study. Of 66 patients undergoing elective operations, 33 were given tranexamic acid (15 mg x kg(-1) before infusion of heparin and 15 mg x kg(-1) after protamine infusion), and the other 33 received only saline. Postoperative bleeding, transfusions, complications, hematological variables, and plasma D-dimer levels were recorded. Postoperative blood loss was significantly less in the tranexamic acid group compared to the control group (320 +/- 38 vs 480 +/- 75 mL). Patients in the tranexamic acid group received significantly less allogeneic blood products (0.46 vs 0.94 units per patient), and they had lower postoperative D-dimer levels. No postoperative thrombotic complications were observed in either group. Although off-pump coronary artery bypass surgery is associated with reduced frequency of hemorrhagic disorders, defective hemostasis still occurs, and tranexamic acid effectively reduces postoperative blood loss and the need for allogeneic blood products. Various clinical trials have shown that hemostasis is improved by the administration of aprotinin during cardiopulmonary bypass. However, this effect has not been proved for those patients treated preoperatively with aspirin. Therefore, a double-blind, placebo-controlled study was conducted to test the efficacy of low-dose aprotinin (2 x 10(6) KIU in the pump prime solution) in preserving hemostasis in 40 aspirin-treated (325 mg) patients undergoing coronary artery bypass grafting. Aprotinin brought about a decrease in the postoperative blood loss (p < 0.05). The in vitro bleeding test (Thrombostat) demonstrated that aprotinin preserved the platelet hemostatic function in aspirin-treated patients during cardiopulmonary bypass (p < 0.05). The inhibitory effects of aspirin on collagen-induced platelet aggregation and thromboxane production were not influenced by aprotinin treatment. The findings from the present study indicate that aprotinin preserves hemostasis in aspirin-treated patients during cardiopulmonary bypass, but aspirin's effect on platelets is maintained. Therefore, aprotinin seems to be a useful adjunct treatment in aspirin-treated patients undergoing coronary artery bypass grafting. Ninety patients undergoing cardiac surgery were randomly divided into three groups of 30 patients to compare the effects on bleeding and transfusion requirements of either intraoperative infusion of high-dose aprotinin (GpI) or reinfusion of autologous fresh whole blood (GpII) versus a control group (GpIII). Standardized anesthetic, perfusion, and surgical techniques were used. Platelet counts, hemoglobin concentration, hematocrit, fibrinogen, and Ivy-Nelson bleeding times determined at fixed times perioperatively did not differ among the three groups. The total loss from the chest drains was significantly reduced in GpI (328 +/- 28 mL; mean +/- SEM) as compared with the loss in GpII and GpIII (775 +/- 75 mL and 834 +/- 68 mL, respectively). There was a threefold difference in the total hemoglobin loss (GpI, 14.2 +/- 1.7 g; GpII, 50.1 +/- 5.0 g; GpIII, 45.0 +/- 5.2 g). GpI patients also received less banked blood: 250 +/- 53 mL versus 507 +/- 95 mL in GpII and 557 +/- 75 mL in GpIII. No GpI patient required transfusion of platelets or fresh frozen plasma. Fresh whole autologous blood transfusions had no significant hemostatic effect and failed to reduce the homologous blood requirement. Conversely, high-dose aprotinin reduced blood loss and transfusion requirements. We studied the hemostatic effects of tranexamic acid in patients undergoing elective surgery involving the thoracic aorta.
                In a double-blind, randomized fashion, 60 consecutive patients were assigned to two treatment groups: 30 patients (placebo group) received infusion of saline solution, and 30 (treatment group) received tranexamic acid (1 g before skin incision, an infusion of 400 mg/h during the operation, and 500 mg in the pump priming). Perioperative bleeding was considered as a primary outcome. Perioperative allogeneic transfusions, major thrombotic complications (myocardial infarction, pulmonary embolism, renal insufficiency), and surgical outcomes were also considered.
                Patients treated with tranexamic acid showed significant reductions in postoperative bleeding, both in terms of the amount collected during the first 4 postoperative hours (median 307 mL, interquartile range 253-361 mL in the placebo group vs median 211 mL, interquartile range 108-252 mL in the treatment group, P =.002) and in terms of total bleeding (median 722 mL, interquartile range 574-952 mL in the placebo group vs median 411 mL, interquartile range 313-804 mL in the treatment group, P =.04). Consequently, the number of patients transfused differed significantly between groups (21 patients [72.4%] in the placebo group vs 13 [44.8%] in the treatment group, P =.033). Patients in the treatment group showed significant reductions in the total amount for the entire group of packed red cells transfused (13,500 mL in the treatment group vs 28,000 mL in the placebo group, P =.012) and in the total amount of allogeneic transfusions (23,400 mL in the treatment group vs 53,000 mL in the placebo group, P =.024). No differences in perioperative thrombotic complications were found.
                In this initial series of patients undergoing thoracic aortic surgery, tranexamic acid appeared effective in reducing perioperative bleeding, with a significant reduction in the need for allogeneic transfusions and without any increased risk of thrombotic complications.
Anti-fibrinolytic drugs provide worthwhile reductions in blood loss and the receipt of allogeneic red cell transfusion. Aprotinin appears to be slightly more effective than the lysine analogues in reducing blood loss and the receipt of blood transfusion. However, head to head comparisons show a lower risk of death with lysine analogues when compared with aprotinin. The lysine analogues are effective in reducing blood loss during and after surgery, and appear to be free of serious adverse effects.