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PubMed2005

Topical treatment of non-healing corneal epithelial ulcers in dogs with aminocaproic acid.

The potential efficacy of topical epsilon-aminocaproic acid, an antiplasmin agent, in the treatment of persistent corneal epithelial defects was evaluated in a study of the medical records of 44 dogs, in which 51 eyes had been diagnosed with a corneal epithelial defect lasting more than 10 days, with no apparent underlying cause. At an initial examination all the affected eyes had had non-adherent epithelium removed. Thirty-four of the eyes in 28 dogs examined between January 2000 and March 2003 were also treated by the topical application of a solution of 35.7 mg/ml ophthalmic aminocaproic acid three times a day; the other 17 eyes in 16 dogs treated between October 1997 and March 1999 had received only topical treatment with gentamicin in addition to the debridement. Both groups were assessed clinically at weekly intervals for a maximum of three weeks. The two groups had approximately the same breed distribution, and there were no statistically significant differences between them in terms of their age, sex, affected side or duration of the corneal erosions. After three weeks, 32 of the 34 eyes treated with aminocaproic acid (94.1 per cent) had been cured, compared with seven of the 17 eyes treated with gentamicin (41.2 per cent) (P=0.0001). No adverse drug reactions were reported.

Administration, Topical↗
PubMed1994

Synthesis and activity of dipeptides containing epsilon-aminocaproic acid.

Five new dipeptides containing epsilon-aminocaproic acid were synthesized. All dipeptides markedly inhibit fibrinolytic activity of plasmin but only in low concentration (0.0002M). In higher concentration fibrinolytic activity was observed. Activity of dipeptides containing epsilon-aminocaproic acid, which antifibrinolytic activity is known, was tested on plasmin, thrombin, urokinase and euglobulin fraction using synthetic substrates.

Amides↗
PubMed1982

Interference with dimethylhydrazine induction of colon tumors in mice by epsilon-aminocaproic acid.

The antifibrinolytic agent epsilon-aminocaproic acid given in the drinking water to Swiss ICR/Ha mice significantly counteracted the appearance of colorectal tumors induced by 21 weekly infections of 1,2-dimethylhydrazine. The drug affected both the number and the location of the tumors and, in some animals, altogether prevented their appearance. The low concentrations of epsilon-aminocaproic acid in the plasma of four control mice given the agent labeled with carbon-14 for 3 days suggest that the effect may depend not on inhibition of plasminogen activator activity, but on interference with the binding of some substance to the strong lysine binding site of plasminogen.

Adenocarcinoma↗
PubMed1997

Cost-benefit and efficacy of aprotinin compared with epsilon-aminocaproic acid in patients having repeated cardiac operations: a randomized, blinded clinical trial.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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).

Adult↗
PubMed1996

Reduction of bleeding after heart operations through the prophylactic use of epsilon-aminocaproic acid.

UNLABELLED: 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. RESULTS: 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. CONCLUSION: The intraoperative use of epsilon-aminocaproic acid reduces postoperative cardiac surgical bleeding.

Aminocaproic Acid↗
PubMed2006

The efficacy and safety of epsilon-aminocaproic acid treatment in patients with cirrhosis and hyperfibrinolysis.

BACKGROUND: Patients with decompensated cirrhosis are at risk for hyperfibrinolysis; this is potentially fatal. epsilon-aminocaproic acid has been used to treat patients with hyperfibrinolysis; however, the data about its benefit in the setting of cirrhosis are minimal. AIM: To analyse the efficacy of epsilon-aminocaproic acid and its safety in cirrhotic patients with hyperfibrinolysis. METHODS: All patients with an abnormal euglobin lysis time who were admitted to Rancho Los Amigos Medical Center from 1 January 2001 to 31 December 2002 were included in the study. Their medical records were reviewed and analysed. RESULTS: There were 60 cirrhotic patients with shortened euglobin lysis time. Fifty-two patients received epsilon-aminocaproic acid. Of the 52 patients, seven had one or more bleeding episodes with the subcutaneous or soft tissue bleeding as the most common indication for epsilon-aminocaproic acid use. Of the 37 patients, 34 (92%) had improvement or resolution of their bleeding. Only two (3%) patients had epsilon-aminocaproic acid treatment discontinued because of minor side effects, rash and lightheadedness. There were no thromboembolic complications of treatment. CONCLUSIONS: epsilon-aminocaproic acid was found to be effective and safe for treatment of hyperfibrinolysis in patients with cirrhosis.

Administration, Oral↗
PubMedDate not supplied

Is epsilon-aminocaproic acid as effective as aprotinin in reducing bleeding with cardiac surgery?: a meta-analysis.

BACKGROUND: Although aprotinin is known to be effective in reducing postoperative hemorrhage after cardiac surgery, epsilon-aminocaproic acid, an alternative antifibrinolytic, is considerably less expensive. Because the results of 3 small randomized clinical trials comparing these 2 agents directly were inconclusive, we performed a meta-analysis to compare the relative effectiveness and adverse-effect profile of these 2 agents against placebo. METHODS AND RESULTS: Data from 52 randomized clinical trials published between 1985 and 1998 involving the use of epsilon-aminocaproic acid (n=9) or aprotinin (n=46) in patients undergoing cardiac surgery were abstracted. Our primary outcomes were total blood loss, red blood cell transfusion rates and amounts, reexploration, stroke, myocardial infarction, and mortality. The meta-analysis revealed substantial reductions in total blood loss with epsilon-aminocaproic acid and low-dose aprotinin (each with a 35% reduction versus placebo, P<0.001) and high-dose aprotinin (53% reduction, P<0.001). There were identical reductions in total postoperative transfusions with epsilon-aminocaproic acid (61% reduction versus placebo, P<0. 010) and high-dose aprotinin (62% reduction, P<0.001). The proportion of patients transfused was similarly reduced with epsilon-aminocaproic acid (OR, 0.32; 95% CI, 0.15 to 0.69) and high-dose aprotinin (OR, 0.28; 0.22 to 0.37). Although both drugs reduced rates of reexploration to similar degrees, this effect was statistically significant only with high-dose aprotinin (OR, 0.39; 0. 24 to 0.61). epsilon-Aminocaproic acid and aprotinin had no effect on risks of postoperative myocardial infarction or overall mortality. CONCLUSIONS: Because the 2 antifibrinolytic agents appear to have similar efficacies, the considerably less-expensive epsilon-aminocaproic acid may be preferred over aprotinin for reducing hemorrhage with cardiac surgery.

Aminocaproic Acid↗
PubMed1995

Clinical evaluation of aminocaproic acid for managing traumatic hyphema in children.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Administration, Oral↗
PubMed2003

A phase III, multicenter, randomized, placebo-controlled clinical trial of topical aminocaproic acid (Caprogel) in the management of traumatic hyphema.

OBJECTIVE: To determine the safety and efficacy of topical aminocaproic acid (Caprogel) in the management of traumatic hyphema. DESIGN: Multicenter, randomized, double-masked, placebo-controlled clinical trial. PARTICIPANTS: A total of 51 patients participated in this trial (power = 36%, 2-tailed test). INTERVENTION: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

Administration, Topical↗
PubMed2004

Comparison of epsilon aminocaproic acid and tranexamic acid in pediatric cardiac surgery.

OBJECTIVE: This study compared the efficacy of aminocaproic acid and tranexamic acid in reducing postoperative blood loss, as well as blood and blood product requirements in children with cyanotic congenital heart disease. DESIGN: A prospective randomized study. SETTING: Cardiac center of a tertiary care, referral hospital. PARTICIPANTS: One hundred fifty children in the age group of 2 months to 14.5 years with cyanotic congenital heart disease undergoing corrective surgery on cardiopulmonary bypass (CPB). INTERVENTIONS: Patients were randomized into 3 groups. Group A was given aminocaproic acid in a dose of 100 mg/kg after anesthetic induction, 100 mg/kg on CPB and 100 mg/kg after protamine. Group T was given tranexamic acid, 10 mg/kg, after anesthetic induction, 10 mg/kg on CPB, and 10 mg/kg after protamine. Group C was the control group. MAIN RESULT: Control group had the longest sternal closure time, maximum blood loss at 24 hours, and maximum requirements of blood and blood products. Among the 2 groups given antifibrinolytics, there was no significant difference in postoperative blood loss, blood and product requirement, and reexploration rates. CONCLUSION: Aminocaproic acid and tranexamic acid are equally effective in reducing postoperative blood loss, as well as blood and blood product requirements in children with cyanotic heart disease undergoing corrective surgery as compared with the control group.

Adolescent↗
PubMed1994

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.

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.

Aged↗
PubMedDate not supplied

Tranexamic acid reduces bleeding after cardiopulmonary bypass when compared to epsilon aminocaproic acid and placebo.

UNLABELLED: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Aminocaproic Acid↗
PubMed2003

Antifibrinolytic therapy during cardiopulmonary bypass reduces proinflammatory cytokine levels: a randomized, double-blind, placebo-controlled study of epsilon-aminocaproic acid and aprotinin.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Aged↗
PubMed1994

Decreased postoperative drainage with addition of epsilon-aminocaproic acid before cardiopulmonary bypass.

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.

Aminocaproic Acid↗
PubMed1995

Antibody to folic acid: increased specificity and sensitivity in ELISA by using epsilon-aminocaproic acid modified BSA as the carrier protein.

For raising high titre and specific antibody to haptens or drugs, epsilon-aminocaproic acid modified bovine serum albumin (epsilon-ACA-BSA) was prepared for use as a carrier protein. Folic acid (FA) was coupled to epsilon-ACA-BSA, Imj.BSA and BSA for raising antibodies in rabbits. Enhancement of FA immunogenicity with FA-ACA-BSA was observed. Apart from determination of titre by indirect ELISA, dose-response behaviour and specificity of these antisera were also compared. FA-ACA-BSA antibody showed high sensitivity and specificity. Using this antibody, an ELISA method for the determination of FA was developed. The study provides a simple approach to raise highly specific and high titre antibody against small molecules.

Aminocaproic Acid↗
PubMed1962

The enhancement of chloroform-induced plasma proteolytic activity by epsilon aminocaproic acid.

The proteolytic activity in chloroform-treated plasma euglobulins has been attributed to plasmin. Plasmin can digest both casein and fibrin. Epsilon aminocaproic acid, which inhibits the activation of plasminogen, the precursor of plasmin, by streptokinase, urokinase, and tissue activators enhanced the development of casein hydrolytic activity in a mixture of chloroform and plasma euglobulins. Fibrinolytic activity was also enhanced, but this was evident only if the epsilon aminocaproic acid was removed from the chloroform-treated euglobulins prior to assay. The reasons for the paradoxical enhancement of chloroform-induced casein hydrolysis by euglobulins containing epsilon aminocaproic acid are unclear. However, studies of optimal pH, heat stability, and the effect of ionic strength on the activation of the precursor of this proteolytic enzyme do not differentiate it from plasminogen.

Amino Acids↗
PubMed1992

Suspected anaphylactoid shock to aminocaproic acid (plaslloid) during operation.

Epsilon-aminocaproic acid (plaslloid) is one of the most common hemostatics used perioperatively. Although some minor untoward effects in association with its use are not uncommon, the incidence of anaphylactoid shock is extremely rare, especially in a patient under general anesthesia. Recently we came across a severe anaphylactoid reaction, possibly as a result of administration of plaslloid in a patient who was undergoing elective surgery for cervical carcinoma. It was manifested by profound hypotension, tachycardia, hypoxemia, skin-wheel eruption and conjunctival and labial edema. She was successfully resuscitated with prompt volume expansion and epinephrine injection. Our experience in the management of this patient is, hereunder, reported and discussed.

Aminocaproic Acid↗