Tranexamic acid reduces red cell transfusion better than epsilon-aminocaproic acid or placebo in liver transplantation. A randomized trial of solvent/detergent-treated and standard fresh-frozen plasma in the coagulopathy of liver disease and liver transplantation. The prophylactic use of tranexamic acid and aprotinin in orthotopic liver transplantation: a comparative study. Aprotinin reduces red blood cell transfusion in orthotopic liver transplantation: a prospective, randomized, double-blind study. Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial. Effects of low central venous pressure during preanhepatic phase on blood loss and liver and renal function in liver transplantation. Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation. The prophylactic effect of aprotinin on intraoperative bleeding in liver transplantation: a randomized clinical study. Does aprotinin really reduce blood loss in orthotopic liver transplantation? Vasopressor administration during liver transplant surgery and its effect on endotracheal reintubation rate in the postoperative period: a prospective, randomized, double-blind, placebo-controlled trial. Continuous small-dose aprotinin controls fibrinolysis during orthotopic liver transplantation. Comparative effects of small and large aprotinin doses on bleeding during orthotopic liver transplantation. Activated recombinant factor VII in orthotopic liver transplantation. Comparison of RBCs and FFP with whole blood during liver transplant surgery. Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease. Coagulation and biochemical effects of balanced salt-based high molecular weight vs saline-based low molecular weight hydroxyethyl starch solutions during the anhepatic period of liver transplantation. Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation. Aprotinin inhibits tissue plasminogen activator-mediated fibrinolysis during orthotopic liver transplantation. Conjugated estrogen reduces transfusion and coagulation factor requirements in orthotopic liver transplantation. Improved haemodynamic stability with administration of aprotinin during orthotopic liver transplantation. Evidence that intraoperative prostaglandin E1 infusion reduces impaired platelet aggregation after reperfusion in orthotopic liver transplantation. Different aprotinin applications influencing hemostatic changes in orthotopic liver transplantation. Aprotinin and transfusion requirements in orthotopic liver transplantation: a multicentre randomised double-blind study. EMSALT Study Group. Continuous small-dose tranexamic acid reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation. Antithrombin III supplementation during orthotopic liver transplantation in cirrhotic patients: a randomized trial. 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.
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. Virus inactivation of pooled fresh-frozen plasma (FFP) by the solvent/detergent (SD) method results in a loss of approximately 20 percent of factor VIII. This study aimed to assess the efficacy of SD-treated plasma in correcting the coagulopathy associated with liver disease and liver transplantation.
                Forty-nine patients with coagulation deficits due to liver disease, who required FFP for invasive procedures or liver transplantation, were randomly assigned to receive either FFP or SD-treated plasma. Patients were assessed for side effects, correction of coagulopathy over 24 hours, and seroconversion for viral markers 6 to 18 months after treatment.
                In the liver disease group, equal correction of clotting factors and partial thromboplastin time was seen with FFP and SD-treated plasma, with a similar return to baseline values over 24 hours. There was greater correction of the International Normalised Ratio in patients receiving SD-treated plasma (p = 0.037), but this patient group had higher baseline values than recipients of FFP (p = 0.024). Liver transplant patients also showed equivalent correction of coagulopathy with the same dose of FFP and SD-treated plasma. The use of other blood components during transplantation was identical in the two treatment groups. No seroconversions were seen for HIV or hepatitis B or C virus. One patient who had received FFP seroconverted for human parvovirus B19. Apparent seroconversion for hepatitis A virus seen at 9 to 13 months in four other patients was probably due to detection of passively transferred antibodies, as later testing of these patients gave negative results. Minor side effects were rare in both groups.
                SD-treated plasma is an efficacious source of coagulation factors for patients with liver disease who are undergoing biopsy or transplantation. Assessment of seroconversion for viral markers in recipients of plasma-derived products and plasma components should include consideration of the possibility that passively transferred antibodies were detected. 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. 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 test in a prospective randomized study the hypothesis that use of thromboelastography (TEG) decreases blood transfusion during major surgery.
                Twenty-eight patients undergoing orthotopic liver transplantation were recruited over 2 years. Patients were randomized into 2 groups: those monitored during surgery using point-of-care TEG analysis, and those monitored using standard laboratory measures of blood coagulation. Specific trigger points for transfusion were established in each group.
                In patients monitored via TEG, significantly less fresh-frozen plasma was used (mean [SD], 12.8 [7.0] units vs 21.5 [12.7] units). There was a trend toward less blood loss in the TEG-monitored patients; however, the difference was not significant. There were no differences in total fluid administration and 3-year survival.
                Thromboelastography-guided transfusion decreases transfusion of fresh- frozen plasma in patients undergoing orthotopic liver transplantation, but does not affect 3-year survival.
                2010 Elsevier Inc. All rights reserved. Although the low central venous pressure (LCVP) technique is used to decrease blood loss during liver resection, its efficacy and safety during transplant procedures are still debatable. Our study aimed to assess the effects of this technique and its clinical safety for recipients undergoing liver transplantation.
                Eighty-six adult patients were randomly divided into a LCVP group and a control group. In the LCVP group, CVP was maintained below 5 mmHg or 40% lower than baseline during the preanhepatic phase by limiting infusion volume, manipulating the patient's posture, and administration of somatostatin and nitroglycerine. Recipients in the control group received standard care. Hemodynamics, blood loss, liver function, and renal function of the two groups were compared perioperatively.
                A lower CVP was maintained in the LCVP group during the preanhepatic phase, resulting in a significant decrease in blood loss (1922 +/- 1429 vs. 3111 +/- 1833 ml, P < 0.05) and transfusion volume (1200 +/- 800 vs. 2400 +/- 1200 ml, P < 0.05) intraoperatively. Compared with the control group, the LCVP group had a significantly lower mean arterial pressure at 2 h after the start of the operation (74 +/- 11 vs. 84 +/- 14 mmHg, P < 0.05), a lower lactate value at the end of the operation (5.9 +/- 3.0 vs. 7.2 +/- 3.0 mmol/l, P < 0.05), and a better preservation of liver function after the declamping of the portal vein. There were no significant differences in perioperative renal function and postoperative complications between the groups.
                The LCVP technique during the preanhepatic phase reduced intraoperative blood loss, protected liver function, and had no detrimental effects on renal function in LT. 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. 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. nan End-stage liver disease (ESLD) is associated with a low systemic vascular resistance due to peripheral vasodilatation. This phenomenon is aggravated by general anesthesia (GA) administered during liver transplantation, resulting in precipitous decreases in blood pressure. The excessive amounts (>3 mL/1 mL blood loss) of IV fluid administered to maintain hemodynamic stability during surgery promotes a fluid shift in the lung, which may lead to hypoxia in the immediate postoperative period. This pathophysiologic state may necessitate endotracheal reintubation and mechanical ventilation of the lungs, thus exposing the patient to a risk for morbidities related to laryngoscopy and endotracheal intubation, including deleterious cardiovascular responses to laryngoscopy, endotracheal damage due to laryngoscopic instrumentation, alteration in pulmonary mechanics secondary to controlled mechanical ventilation of the lungs, and delayed recovery associated with the sedation needed to perform these maneuvers.
                The aim of this study was to determine whether the use of a vasopressor to antagonize the vasodilatory effect of GA would reduce the amount of IV fluids administered during liver transplantation, and whether the subsequent amelioration of fluid shift in the postoperative period would reduce the need for ventilatory support and endotracheal reintubation.
                This prospective, randomized, double-blind, placebo-controlled study was conducted at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey. Patients aged > or =18 years scheduled to undergo orthotopic liver transplantation for ESLD were enrolled. The effect of use of an adjuvant vasopressor, together with controlled fluid administration (ie, the volume of IV fluid needed to maintain hemodynamic parameters at > or =80% of preoperative levels) (vasopressor group), was compared with that of fluid administration only (placebo group). We determined various postoperative outcome measures, primarily the amount of fluid administered and the need for endotracheal reintubation.
                Sixty-five patients were enrolled (44 men, 21 women; vasopressor, 33 patients; placebo, 32 patients). Sex distribution showed 19 men and 14 women in the vasopressor group and 25 men and 7 women in the placebo group (both, P < 0.05). The 2 treatment groups were statistically similar with regard to the rest of the baseline demographic and clinical characteristics and duration of surgery. The vasopressor group had a significantly lower prevalence of endotracheal reintubation compared with the placebo group (RR, 1:6; P < 0.05). The other postoperative parameters were statistically similar between the 2 groups.
                In this study of adults undergoing orthotopic liver transplantation for ESLD, use of an adjuvant vasopressor, together with controlled fluid administration, to maintain a stable hemodynamic status during GA reduced the need for endotracheal reintubation and its associated morbidities in the postoperative period compared with placebo. 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. Large prophylactic doses of aprotinin efficiently reduce blood loss during orthotopic liver transplantation (OLT). Small doses of aprotinin are usually used to treat fibrinolysis. However, no studies have investigated the benefit of prophylactic administration of a smaller dose of aprotinin during liver transplantation. We compared two methods of aprotinin therapy on transfusion outcome in liver transplant patients in a prospective study of 199 patients undergoing OLT who were randomized to large or small prophylactic doses of aprotinin during the transplant procedure. In the large-dose group (n = 94) an initial dose of 2,000,000 kallikrein inactivation units (KIU) was followed by infusion of 500,000 KIU/h until the patient's return to the intensive care unit. In the small-dose group (n = 95), an initial dose of 500,000 KIU was followed by an infusion of 150,000 KIU/h. Outcome measurements included intraoperative transfusion requirements (packed red blood cells, fresh frozen plasma, platelets, intraoperative salvage) and postoperative hematologic values. There were no differences in transfusion requirements in the two groups of patients. Patients treated with low-dose aprotinin had slightly higher postoperative fibrinogen concentrations. Large-dose aprotinin therapy does not appear to offer additional benefit compared to low-dose aprotinin administration. Orthotopic liver transplantation (OLT) is affected by important alterations of hemostasis. The aim of this study was to evaluate the efficacy of recombinant factor VII activated (rFVIIa) to reduce intraoperative bleeding during OLT.
                Twenty OLT patients were assigned in double-blind way to a rFVIIa group or a control group. Inclusion criteria were hemoglobin > 8 g/dL: INR > 1,5 and fibrinogen > 100 mg/dL. We administered a single bouls of rFVIIa (40 microg/kg) or placebo. We determined INR, partial thromboplastin time, fibrinogen, ATIII, and blood cell counts. Blood products were administered as follows: 4 units of fresh frozen plasma when INR > 1.5, and 1 unit of RBC for Hb < 10 g/dL. The study ended 6 hours after the bolus.
                No thromboembolic events occurred. The INR was different between rFVIIa group and the controls at T0 (1.9 vs 1.6 P < .021) and during T1 (1.2 vs 1.6 P < .004). The total transfused red blood cells was 300 mL +/- 133 in rFVIIa group and 570 mL +/- 111 in control group (P < .017). The total fresh frozen plasma was 600 mL +/- 154 in rFVIIa group and 1400 mL +/- 187 in control group (P < .001). Total blood loss was greater in the control group than the rFVIIa group: 1140 mL +/- 112 vs 740 mL +/- 131 (P < .049).
                The use of rFVIIa during OLT can reduce the risk of bleeding during surgery. The literature has described cases who did not benefit from the treatment. An adequate cut-off of INR, allowed us to treat only patients at greater bleeding risk. Component therapy has become the accepted standard of care in transfusion medicine. In instances of large blood loss, the transfusion of whole blood rather than the combination of RBCs and FFP is rational and may be preferred.
                In a controlled, prospective, randomized study of 33 patients undergoing orthotopic liver transplantation, the effectiveness of component therapy (RBCs and FFP) was compared with the use of whole blood. Coagulation tests (prothrombin time and activated partial thromboplastin time), clotting factor levels (FV, FVIII, fibrinogen), platelet counts, the number of donor exposures, and the total volume of blood transfused for the whole-blood group and the component-therapy group were compared at designated times before surgery, during surgery, and 24 hours after surgery.
                There was a significant difference (p=0.015) in the median number of donor exposures for RBCs and FFP, with fewer occurring in the whole-blood group (n=14.5) compared with the component group (n=25). There was no significant difference between groups in coagulation profiles during any of the phases of surgery except for a mild decrease in fibrinogen levels in the whole-blood group at the conclusion of surgery. There were no differences between the groups in the median volume of blood component replacement, the median age of blood components, the patients' Hct or the number of RBC-containing components transfused.
                Whole blood, when compared with component therapy, is associated with fewer donor exposures yet provided equally effective replacement therapy for blood loss in liver transplantation patients. Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however, there has been a limited amount of research into its use in OLT. The purpose of this dose-finding study was to examine the efficacy and safety of rFVIIa in the reduction of bleeding in patients undergoing OLT. In this double-blind trial, patients with end-stage liver disease scheduled for OLT were randomized to 1 of 4 parallel study groups. They received a single intravenous bolus of rFVIIa (20, 40, or 80 microg/kg) or placebo prior to surgery. The primary assessment endpoint was the total number of red blood cell (RBC) units transfused perioperatively. Safety was evaluated by adverse events reported. Eighty-three comparable patients were randomized to receive study product, with 82 ultimately undergoing OLT. There were no significant differences in required RBC units between the placebo and rFVIIa study groups. The number of adverse events was comparable between study groups. In conclusion, rFVIIa has a good safety profile in patients undergoing OLT. However, the doses studied did not have any effect on the number of RBC transfusions required. The anhepatic period of liver transplantation is generally marked by a decrease in preload, and the infusion of hydroxyethyl starch (HES) solution is often an effective way to restore volume deficits in non-anaemic patients. However, the infusion of even limited amounts of HES solution during the anhepatic period may result in a worsening coagulopathy. Moreover, lactate-containing HES solution may cause some degree of biochemical derangements in compromised recipients. Therefore, we compared two different types of HES solutions: a balanced salt-based high molecular weight HES solution (670/0.75; high MW group) and a saline-based low molecular weight HES solution (130/0.4; low MW group) with respect to coagulation and biochemical profiles. First, in an in vitro study (n = 48), thromboelastography was performed to determine the effects of two HES solutions on coagulation after diluting (11%) the recipient's blood sample with each HES solution. Second, in an in vivo study, 500 ml of one of the two 6% HES solution was administered to 74 recipients (n = 37, each group) for 30 min after starting the anhepatic period. The coagulation profiles, including thromboelastography, and biochemical profiles were measured before and 30 min after the end of infusion. Less impairment in the thromboelastography profiles and aPTT was observed in the high MW group. A higher calcium concentration and less reduction in platelet count were noted in the high MW group, but lactate accumulation was greater. In conclusion, a balanced salt-based high molecular weight HES solution is a more effective volume replacement during the anhepatic period of liver transplantation with respect to coagulation than a saline-based low molecular weight HES solution, although lactate accumulation is a possible concern. Patients undergoing orthotopic liver transplantation (OLT) have excessive blood loss during surgery that requires blood transfusions, leading to increased postoperative morbidity and mortality. We studied the efficacy and safety of activated recombinant factor VII (rFVIIa) in reducing transfusion requirements in OLT. This multicenter, randomized, double-blind, placebo-controlled trial enrolled patients undergoing OLT because of cirrhosis (Child-Turcotte-Pugh class B or C). Patients received a repeated intravenous bolus regimen of rFVIIa 60 or 120 microg/kg or placebo. The primary efficacy endpoint was the total number of red blood cell (RBC) units transfused during the perioperative period. A total of 182 patients were analyzed for efficacy and 183 for safety. No significant effect of rFVIIa was observed on the number of RBC units transfused or intraoperative blood loss compared with the placebo group. A significantly higher number of patients in the rFVIIa study groups avoided RBC transfusion. Administration of rFVIIa but not placebo restored the preoperative prolonged prothrombin time to normal value during surgery. Patients receiving rFVIIa and placebo did not experience a significant difference in rate of thromboembolic events. Additionally, there was no statistically significant effect of rFVIIa treatment on hospitalization rate, total surgery time, and the proportion of patients undergoing retransplantation. In conclusion, use of rFVIIa during OLT significantly reduced the number of patients requiring RBC transfusion. There was no increase in thromboembolic events with rFVIIa administration compared with placebo. nan We conducted a prospective, randomized study to determine the efficacy of conjugated estrogen in reducing blood product transfusion during orthotopic liver transplantation (OLT). Patients undergoing OLT were included in the study. Only those having a reaction time of more than 30 mm or 15 min (19 -28 mm) on computed thromboelastography (CTEG) at the beginning of surgery were enrolled in the study. Patients were randomized to receive either conjugated estrogen (CE) or placebo. Every patient received a first dose of CE (100 mg i.v.) (20 mL) or placebo (20 mL of isotonic sodium chloride solution) at the beginning of the procedure and a second dose of CE (100 mg i.v.) or 20 mL of placebo (20 mL of isotonic sodium chloride solution) just after reperfusion of the new graft. The two groups were similar in age, weight, requirement for veno-veno bypass, time on veno-veno bypass, CTEG measurement, and preoperative hemoglobin and platelet values. Blood products were given in relation to hematocrit and coagulation (CTEG) variables, which were measured every hour during the surgery. The amount of transfused blood products did not differ in terms of units of cryoprecipitate, but the intraoperative requirements for red blood cells (6 +/- 3 vs 9 +/- 6 U; P = 0.05), platelets (12 +/- 8 U vs 18 +/- 10 U; P = 0.05) and fresh-frozen plasma (3 +/- 3 U vs 6 +/- 4 U; P = 0.001) was significantly less in the estrogen group than in the control group. We conclude that CE is associated with a significant decrease in use of fresh-frozen plasma, platelets, and red blood cells during OLT. Implications: In this study, we prospectively investigated whether i.v. conjugated estrogen could decrease blood product transfusion during orthotopic liver transplantation. Conjugated estrogen-treated patients received less fresh-frozen plasma, red blood cells, and platelets. In this population of patients, conjugated estrogen can be a useful addition in coagulation management during orthotopic liver transplantation. In a placebo-controlled, double-blind study, we have investigated the hypothesis that patients for orthotopic liver transplantation (OLT) treated with high-dose aprotinin (serum concentrations > or = 200 kiu ml-1) show greater haemodynamic stability on graft reperfusion. We studied 55 adult patients presenting for OLT, and 52 were included in the analysis. The treatment and placebo groups were similar in patient characteristics. The anaesthetic regimen used was standardized, and veno-venous bypass were used in all patients. Cardiac output measurements and haemodynamic profiles were recorded at intervals throughout anaesthesia and surgery. Arterial and mixed venous oxygen saturations were measured by co-oximetry. Derived variables were measured using standard formulae. Aprotinin treated patients had greater values for systemic vascular resistance on reperfusion, with a lesser cardiac index and calculated oxygen delivery. Oxygen consumption, however, was significantly greater, despite reduced delivery. Recent investigations measuring platelet aggregation during 10 orthotopic liver transplantations showed a significant decrease in platelet aggregation immediately after reperfusion and in the perfusate. As prostaglandin E1 has been shown to exhibit a beneficial effect in the treatment of ischemic injury of the liver, we investigated in a prospective, randomized, and open study the effect of PGE1 infusion during OLT on platelet function. Ten patients were randomized to receive a continuous PGE1 infusion (PG group) and another ten patients served as controls. Platelet function was determined ex vivo by measuring the adenosine diphosphate-, collagen-, and ristocetin-induced aggregation in platelet-rich plasma. A significantly higher platelet aggregability was measured in the PG group throughout the whole operation for ADP (1 and 2 mumol/L) and collagen (0.5 micrograms/ml). The same was true for collagen (1 microgram/ml) and ristocetin (1.2 mg/ml) after reperfusion. Not only the postreperfusional decrease in platelet aggregation but also the decline in platelet count that occurred in the control group could be prevented greatly by PGE1 infusion. In the perfusate, released from the liver graft vein by flushing with arterial blood, a significantly lower platelet aggregability was seen in comparison with the systemic circulation before reperfusion in the control group, a difference that was not found when PGE1 infusion was given intraoperatively. However, blood product requirements during OLT were comparable in both groups. In conclusion, PGE1 therapy during OLT preserves platelet function and prevents the drop in platelet count observed in the control group after revascularization. The effect of different aprotinin applications on hemostatic changes and blood product requirements in orthotopic liver transplantation was investigated in a prospective, open, and randomized study. From November 1989 to June 1990, 13 patients received aprotinin as a bolus of 0.5 Mill. Kallikrein inactivator units (KIU) on three occasions in the course of an OLT, whereas 10 other patients were treated with continuous aprotinin infusion of 0.1-0.4 Mill. KIU/hr. Before and after reperfusion of the graft liver, signs of hyperfibrinolysis, measured by thrombelastography, were significantly lower in the infusion group. Tissue-type plasminogen activator (t-PA) activity increased during the anhepatic phase but to a significantly lesser extent in the infusion group. Blood product requirements during OLT were tendentiously higher in the bolus group but not significantly so. However, the use of packed red blood cells was significantly lower in the postoperative period, whereas there was no significant difference in fresh frozen plasma requirements between the two groups. All 23 patients have survived, and only one woman of each group required retransplantation due to severe host-versus-graft reactions. Furthermore, we investigated the perfusate of the graft liver in both groups and detected signs of a decreased t-PA release in the infusion group. Our results demonstrate an advantage of aprotinin given as continuous infusion over bolus application in OLT. 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 (TA) is a synthetic drug that inhibits fibrinolysis. It has been administered to decrease the use of blood products during cardiac surgery and orthotopic liver transplantation when infused in larger doses. A small-dose infusion of aprotinin causes a reduction in fibrinolysis and blood product requirement during orthotopic liver transplantation without apparent risk of intravascular thrombosis. This prospective study was designed to investigate whether a small-dose infusion of TA would be equally effective in reducing fibrinolysis and blood product transfusions during orthotopic liver transplantation. A double-blind, controlled study was undertaken to compare the efficacy of a small-dose TA infusion with that of a placebo. Thirty-two consecutive patients were randomized either to the TA group (n = 16), which received an intravenous infusion of 2 mg x kg(-1) x h(-1), or to the control group (n = 16), which received an identical volume of normal saline. Coagulation values were measured, a field rating was made by the surgeon, and a thromboelastogram was produced at four predetermined intervals throughout the case-before TA infusion was started, after portal vein ligation, 10 min after reperfusion, and at the end of surgery. Intraoperative transfusion requirements were recorded during the procedure and for the first 24 h postoperatively. A record was kept of any intraoperative epsilon-aminocaproic acid administered for uncontrolled fibrinolysis. The thromboelastogram clot lysis index was significant for lysis in the control group during both the anhepatic and the neohepatic phases (P < 0.01 and P < 0.05, respectively) when compared with the TA group. Fibrin degradation products were significantly increased (>20 microg/mL) in the control group at reperfusion (P < 0.03) and at the end of surgery (P < 0.01). D-dimers were also significantly increased (>1 mg/L) in the control group at the end of surgery (P < 0.04). Nine of the 16 control patients versus 3 of the 16 TA patients required epsilon-aminocaproic acid rescue for fibrinolysis. There were no other significant differences between groups. Transfusion requirements during surgery and for the first 24 h postoperatively did not differ significantly between the two groups. We conclude that the use of small-dose TA reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation. Severe intraoperative bleeding is one of the main problems during liver transplantation. Acquired hemostatic defects, namely primary or secondary hyperfibrinolysis, are considered significant pathogenetic events. Antithrombin III (ATIII), the main physiological serine protease inhibitor, has a critical role in the regulation of hemostasis. 29 patients with post necrotic cirrhosis undergoing liver transplantation were randomized to receive or not ATIII replacement therapy before the induction of anaesthesia and thereafter throughout surgery. Activation of both coagulation and fibrinolysis (increase of thrombin-antithrombin complexes, fibrin and fibrinogen degradation products) were demonstrated in both groups. Blood loss and transfusion requirements were not affected by ATIII administration. 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.
Aprotinin, recombinant factor VIIa, and thromboelastography groups may potentially reduce blood loss and transfusion requirements. However, risks of systematic errors (bias) and risks of random errors (play of chance) hamper the confidence in this conclusion. We need further well-designed randomised trials with low risk of systematic error and low risk of random errors before these interventions can be supported or refuted.