A phase III, multicenter, randomized, placebo-controlled clinical trial of topical aminocaproic acid (Caprogel) in the management of traumatic hyphema. Aminocaproic acid decreases secondary hemorrhage after traumatic hyphema. Aminocaproic acid in the treatment of traumatic hyphema. Aminocaproic acid versus prednisone for the treatment of traumatic hyphema. A randomized clinical trial. Clinical evaluation of aminocaproic acid for managing traumatic hyphema in children. Topical aminocaproic acid to prevent rebleeding in cases of traumatic hyphema. Traumatic hyphema: its clinical characteristics and failure of estrogens to alter its course. A double-blind study. A comparison of two dose regimens of epsilon aminocaproic acid in the prevention and management of secondary traumatic hyphemas. Tranexamic acid and traumatic hyphaema. A prospective study. The management of traumatic hyphema. Monocular versus binocular patching in traumatic hyphema. Comparison of tranexamic acid and prednisolone in the treatment of traumatic hyphema. A randomized clinical trial. The effect of tranexamic acid on secondary haemorrhage after traumatic hyphaema. The treatment of contusion of the eye. Traumatic hyphema. The role of tranexamic acid (Cyklokapron) in the treatment of traumatic hyphaema. Topical aminocaproic acid in the treatment of traumatic hyphema. Traumatic hyphema. Failure of steroids to alter its course: a double-blind prospective study. Aminocaproic acid reduces the risk of secondary hemorrhage in patients with traumatic hyphema. Aspirin and secondary bleeding after traumatic hyphema. Traumatic hyphema in children. Treatment with epsilon-aminocaproic acid.
To determine the safety and efficacy of topical aminocaproic acid (Caprogel) in the management of traumatic hyphema.
                Multicenter, randomized, double-masked, placebo-controlled clinical trial.
                A total of 51 patients participated in this trial (power = 36%, 2-tailed test).
                Patients presenting with traumatic hyphema were randomly assigned to 5-day treatment with topical aminocaproic acid or a placebo gel. Patients were monitored daily with ocular examination and vital sign testing for the 5 days of treatment and at 24 and 48 hours after treatment. General physical examination and laboratory testing were performed at baseline and day 5.
                The main efficacy variable was the rate of rebleeding. Secondary efficacy variables included time to hyphema clearance, intraocular pressure, time to secondary hemorrhage, and visual acuity. Safety variables included adverse events, vital signs, and laboratory measurements.
                Rebleeding occurred in 30% of the placebo group (8 of 27; 95% confidence interval [CI] = 14-50%), versus 8% of the treatment group (2 of 24; 95% CI = 1-27%), for an estimated continuity-corrected difference in percentage of patients with bleeding of 17% (95% CI = -3-38%). Secondary efficacy variables were similar in the groups, except that there was a trend towards more visual improvement in the topical aminocaproic acid group (54%) than in the placebo group (30%) at the last measurement (P = 0.08). Adverse events were similar.
                This study provides evidence that topical aminocaproic acid is safe and demonstrates trends towards reducing the rebleeding rate in the management of traumatic hyphema. However, because the study was terminated before complete enrollment, more definitive recommendations will require a larger trial. Forty-eight patients (49 eyes) had nonperforating traumatic hyphema. Twenty-eight patients (28 eyes with hyphema) received oral aminocaproic acid, an antifibrinolytic agent, in a dosage of 100 mg/kg every four hours for five days, up to a maximum daily dose of 30 g. Twenty patients (21 eyes with hyphema) received placebo in an identical regimen. One eye treated with aminocaproic acid rebled; seven eyes receiving the placebo rebled. The results of this study show a statistically significant reduction in the incidence of secondary hemorrhage in the patients receiving aminocaproic acid. Of 59 patients with traumatic hyphema studied prospectively, 32 received aminocaproic acid, an antifibrinolytic agent, to prevent secondary hemorrhage. The remaining 27 patients received placebo in an identical manner. Of the aminocaproic acid-treated patients, only one (3%) rebled, while nine patients (33%) receiving placebo suffered secondary hemorrhage. The results of this study indicate a statistically significant reduction (P less than .01) in the incidence of rebleeding in patients treated with this drug. One hundred twelve patients who sustained hyphema after blunt trauma were enrolled in a double-blind randomized clinical trial to determine the relative efficacies of aminocaproic acid (Amicar) and systemic prednisone for reducing the rate of secondary hemorrhage. Fifty-six patients received an oral dosage of 50 mg/kg of aminocaproic acid every 4 hours for 5 days, up to a maximum of 30 g daily, and 56 patients received an oral dosage of 40 mg of prednisone daily (adjusted for weight) in two divided doses. Placebo pills and liquids were given to each patient to mask the treatment schedules. There were no statistically significant differences between the patient populations for any demographic or clinical characteristic (e.g., visual acuity, intraocular pressure [IOP], initial hyphema size) measured in the study. Blacks comprised 53% of the study population, and the mean age of the patients was 23.5 years. Four patients in each of the treatment groups experienced a secondary hemorrhage; the rebleed rate was 7.1% in each group. The purpose of this study is to determine the incidence of secondary hemorrhage after traumatic hyphema in children and to evaluate the efficacy of epsilon aminocaproic acid in reducing this incidence.
                In a prospective, randomized, double-blind study performed between November 1987 and February 1994, 94 children admitted for traumatic hyphema were assigned to receive either aminocaproic acid (n = 48) (100 mg/kg every 4 hours; maximum, 30 g daily) or placebo (n = 46) for 5 days. Patients who had ingested aspirin in the week preceding admission were excluded from the study.
                Mean age of the patients was 9.4 years. Black patients comprised 4% of the study population. Secondary hemorrhage occurred in only three patients (3.2%), two from the placebo group and one from the aminocaproic acid group, none of whom had any complications. The duration of hospital stay and the clot resorption times were increased significantly in the aminocaproic acid group (P < 0.001).
                The authors report a very low incidence of secondary hemorrhage compared with most previous studies. This difference is likely related to the small proportion of black patients in our study and to the exclusion of patients having ingested aspirin, two factors that seem to be associated with higher rates of rebleeding. The efficacy of aminocaproic acid could not be determined due to the low incidence of hemorrhage. The results of this study, however, suggest that the incidence of secondary hemorrhage in white patients without prior ingestion of aspirin is insufficient to justify routine use of aminocaproic acid in managing traumatic hyphema. Rather, an individualized decision based on the risk factors of each patient would seem more appropriate to avoid a slower clot resorption time and possible side effects of this medication. To determine the effect of topical aminocaproic acid on the incidence of rebleeding after traumatic hyphema.
                This randomized double blind clinical trial investigated 132 consecutive cases of traumatic hyphema referred to the emergency room of Farabi Eye Hospital in 1998-1999. The patients were randomly divided into three groups: Group 1 received cycloplegic drops only. Group 2 received cycloplegic drops and 2% carboxy polymethylene (CPM) gel as placebo. Group 3 was treated with cycloplegic drops and 25% aminocaproic acid (ACA) in CPM gel (supplied by Messrs. Sina Darou). All patients were treated for five days on an outpatient basis, with a two-week follow-up. The incidence of rebleeding, time needed for clot absorption, and complications of hyphema were recorded and analyzed using the chi-square and Student's t-tests and logistic regression modeling.
                Rebleeding occurred in 8 eyes of 52 patients in group 1 (15.4%), 7 eyes of the 39 patients in group 2 (17.9%) and 5 eyes of the 41 patients in group 3 (12.2%). This difference was not significant. The time needed for clot absorption in groups 1, 2 and 3 was respectively 9.5 +/- 3.9, 9.3 +/- 4.2 and 11.15 +/- 4.7 days, the difference between group 3 and the other two groups being statistically significant (p<0.04).
                Topical 25% ACA is not effective in reducing the incidence of rebleeding and lengthens the time needed for clot absorption. nan Fifty-nine patients who sustained hyphema following blunt trauma were randomly assigned prospectively to either of two dose regimens of epsilon aminocaproic acid (Amicar). Twenty-six took an oral dosage of 50 mg/kg ("half dose") every four hours for five days, up to a maximum of 30 g/day, and 33 patients received 100 mg/kg ("full-dose") every four hours up to a maximum of 30 g/day. Five patients in the full-dose group experienced dizziness, hypotension, and syncope. Half-dose Amicar substantially reduced such serious side effects (P = 0.063), had no adverse effect on the reduced rate of recurrent hemorrhages (P = 0.22), and was more cost effective than the full-dose regimen. When the two patients in the half-dose group receiving 30 g/day of Amicar were deleted, however, the comparison of dizziness and hypotension in the two groups became more significant (P = 0.050). The incidence of nausea and vomiting was approximately the same in both groups (P = 0.52). Serum Amicar levels were within the range of plasminogen inhibition at both dose levels. Prior aspirin ingestion appeared to have no influence on the rate of rebleeding (P = 0.58). 112 patients with traumatic hyphaema were investigated prospectively over a period of 3 years. 53 had conservative treatment and 59 tranexamic acid treatment. They were hospitalized, but fully mobilized. Both groups were given supplementary local therapy with glucocorticoids and mydriatics as well as monocular patching. In neither group was any re-bleeding seen. The resorption of blood was delayed in the tranexamic treated patients, which may be taken as indirect proof of the efficacy of the treatment. The longer persistence of blood in the anterior chamber in the tranexamic acid treated group caused no complication. The treatment was well tolerated. In both departments treatment with tranexamic acid had replaced the bed rest treatment. nan nan Oral antifibrinolytics, oral steroids, and no oral treatment are the preferred medical treatments for traumatic hyphema. Antifibrinolytics and steroids have decreased the chance of rebleeding in some studies but failed to alter the clinical course in others. Rate of secondary hemorrhage seems variable among different geographic and ethnic groups of patients. Comparison of the treatments in each population is necessary to document the most effective method of preventing recurrent hemorrhage.
                Randomized, placebo-controlled, clinical trial.
                Two hundred thirty-eight patients in whom hyphema developed after a blunt trauma entered the study.
                Eighty patients received 75 mg/kg per day oral tranexamic acid (TA) divided into 3 doses, 80 patients received a placebo with the same number of tablets and frequency as those of the TA group, and 78 patients received 0.75 mg/kg per day oral prednisolone divided into 2 doses.
                Secondary hemorrhage during the hospital course was measured.
                Secondary hemorrhage occurred in 8 patients (10%) of the TA group, 14 patients (18%) of the prednisolone group, and 21 patients (26%) of the placebo group. The difference between the incidence of rebleeding between TA and placebo groups was statistically significant (P = 0.008). Patients receiving a placebo had a greater chance of secondary bleeding than did patients receiving TA (odds ratios = 3.2; 95% confidence interval = 1.3, 7.5). The incidences of rebleeding were not significantly different in placebo versus prednisolone groups (P = 0.21) and TA versus prednisolone groups (P = 0.15).
                In a population with a high rate of secondary bleeding, TA is more effective than oral prednisolone or no oral treatment in preventing rebleeding among patients with traumatic hyphema. During the period from March 1978 to November 1979, 232 consecutive patients with traumatic hyphaema were allocated by admission-date to conservative treatment and to treatment with the antifibrinolytic drug tranexamic acid. Secondary haemorrhage occurred in only two of 102 tranexamic acid treated patients, while secondary haemorrhage occurred in 12 out of 130 conservatively treated patients. This difference was statistically significant. Some clinical aspects of the rebleeding cases are presented and briefly discussed. nan nan nan To determine whether topically applied aminocaproic acid, like systemic aminocaproic acid, effectively reduces secondary hemorrhage after hyphemas and to compare the safety and effectiveness of topical application with those of systemic use and a control group.
                A prospective, randomized, double-masked, multicenter study.
                Sixty-four patients with traumatic hyphema treated with topical or systemic aminocaproic acid and compared with 54 control patients with hyphema. Daily slitlamp examinations for hyphema grading and corneal clarity, initial and final visual acuity, applanation tonometry, and fundus indirect ophthalmoscopy were studied. Follow-up was 6 months to 5 1/2 years (mean, 2.96 years).
                Compared with the control group, topical and systemic aminocaproic acid was statistically significant in preventing secondary hemorrhage. Only 3% (2/64) of the patients who received topical or systemic aminocaproic acid had secondary hemorrhage compared with 22% (12/54) of the control group (P = .002). Final visual acuity was 20/40 or better in 30 patients (86%) in the topical group compared with 23 patients (43%) in the control group (P < .001). Final visual acuity was 20/40 or better in 20 patients (69%) in the systemic aminocaproic acid group compared with 23 patients (43%) in the control group (P = .04). The topical aminocaproic acid group had a final visual acuity of 20/40 or better in 86% of patients, compared with 69% of patients in the systemic group.
                Topical aminocaproic acid appears to be a safe, effective treatment to prevent secondary hemorrhage in traumatic hyphema. It is as effective as systemic aminocaproic acid in reducing secondary hemorrhage. No systemic side effects were observed with topical use. Topical aminocaproic acid provides an effective out-patient treatment for traumatic hyphemas. Forty-three patients with traumatic hypema were studied prospectively in a controlled, double-blind study. Twenty-three patients received prednisone and 20 received a lactose placebo. Secondary hemorrhages occurred in 16% of all patients. There was no significant difference in the incidence of secondary hemorrhage between the two groups (P = .85). There is no evidence that prednisone (40 mg/day) decreases the incidence of secondary hemorrhage. There was no significant difference in final visual acuities between the two groups. Patients with initially larger hyphemas do not appear to have worse final visual acuities. Hyphemas without secondary hemorrhage had a uniformly good prognosis. Although final visual acuities were worse in eyes with secondary hemorrhage, associated ocular injuries rather than blood-related complications accounted for the decreased visual acuity. In a prospective, randomized, double-masked study, 34 patients (34 eyes) with nonperforating ocular injury and traumatic hyphema were treated with either aminocaproic acid (Amicar), 100 mg/kg every four hours, up to a maximum of 30 g/d, or placebo for five days. None of 21 patients who were treated with aminocaproic acid rebled, while three (23%) of 13 patients who were treated with placebo rebled. This difference was statistically significant. Of the three patients who rebled, two required surgical intervention, with one patient requiring four surgical procedures. Although complications following aminocaproic acid therapy included light-headedness, nausea and vomiting, and systemic hypotension, only one patient was withdrawn from the study because of drug-related adverse reactions. This study strongly confirms that aminocaproic acid therapy significantly reduces the incidence of secondary hemorrhage following traumatic hyphema. A randomized, controlled study was conducted in 51 patients to investigate the effect of aspirin administration on traumatic hyphema. Aspirin tablets 500 mg tid were administered for seven days. Rebleeding was found in three of 23 eyes of patients who had received aspirin and in two of 28 eyes of control patients. This difference was not statistically significant (P = .405), proving that aspirin is not an important factor in rebleeding in patients with hyphema. Forty-nine patients, ages 3 to 18 years, who sustained nonpenetrating unilateral trauma with hyphemas were assigned randomly to receive either 100 mg/kg of epsilon-aminocaproic acid (EACA), an antifibrinolytic agent, orally every 4 hours for 5 days (maximum 30 g/day) or a placebo. No patients ingested acetylsalicylic acid (ASA)-containing compounds before or during admission. Two patients of 24 treated with EACA and 1 of 25 given placebo had rebleeds. The hyphemas in the EACA-treated group took significantly longer to clear (mean, 5.3 versus 2.6 days; P less than 0.001). Because of the low incidence of rebleeds in the placebo group, the efficacy of EACA in reducing the rate of rebleeds could not be determined. Further studies with this drug, controlling for age, race, sickle trait, and pre-admission antiplatelet agents should be undertaken before its routine use in traumatic hyphema management can be recommended.
Traumatic hyphema in the absence of other intraocular injuries, uncommonly leads to permanent loss of vision. Complications resulting from secondary hemorrhage could lead to permanent impairment of vision, especially in patients with sickle cell trait/disease. We found no evidence to show an effect on visual acuity by any of the interventions evaluated in this review. Although evidence is limited, it appears that patients with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhaging. However, hyphema in patients on aminocaproic acid take longer to clear.
Other than the possible benefits of antifibrinolytic usage to reduce the rate of secondary hemorrhage, the decision to use corticosteroids, cycloplegics, or non-drug interventions (such as binocular patching, bed rest, or head elevation) should remain individualized because no solid scientific evidence supports a benefit. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.