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At least 235 records · Page 13Linked to original sources
PubMed1998

High-dose epsilon-aminocaproic acid versus aprotinin: antifibrinolytic efficacy in first-time coronary operations.

BACKGROUND: The antifibrinolytic efficacy of a high-dose regimen of epsilon-aminocaproic acid (epsilon-ACA) was compared with aprotinin in first-time coronary operations. METHODS: 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. RESULTS: 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. CONCLUSIONS: In first-time coronary operations, higher postoperative hematocrit and less shed blood retransfusion constitute only subtle advantages of aprotinin over high-dose epsilon-ACA.

Aminocaproic Acid↗
PubMed1996

Crystal structures of the recombinant kringle 1 domain of human plasminogen in complexes with the ligands epsilon-aminocaproic acid and trans-4-(aminomethyl)cyclohexane-1-carboxylic Acid.

The X-ray crystal structures of the complexes of the recombinant kringle 1 domain of human plasminogen (Klpg) with the ligands epsilon-aminocaproic acid (EACA) and trans-4-(aminomethyl)cyclohexane-1-carboxylic acid (AMCHA), which are representative of a class of in vivo antifibrinolytic agents, have been determined at 2.1 angstroms resolution. Each Klpg/ligand unit cell contained a dimer of the complexes, and some small differences were noted in the kringle/ligand interatomic distances within the monomeric components of the dimers. The structures obtained allowed predictions to be made of the amino acid residues of Klpg that are likely important to ligand binding. In the crystal structure, the anionic center of Klpg responsible for coordinating the amino group of the ligands is composed of both Asp54 and Asp56, and the cationic center that stabilizes binding of the carboxylate moiety of the ligands is Arg70, with a possible contribution from Arg34. A hydrogen bond between the carboxylate of the ligand to the hydroxyl group of Tyr63 also appears to contribute to the kringle/ligand binding energies. The methylene groups of the ligand are stablized in the binding pocket by van der Waals contacts with side-chain atoms of Trp61 and Tyr71. These conclusions are in general agreement with site-directed mutagenesis results that implicate many of the same amino acid residues in the binding process, thus showing that the crystal and solution structures are in basic accord with each other. Further comparisons of the X-ray crystal structures of the Klpg/ligand complexes with each other and with apo-Klpg show that while small differences in Klpg side-chain geometries may exist in the three structures, the binding pocket can be considered to be preformed in the apokringle and not substantially altered by the nature of the omega-amino acid ligand that is inserted into the site. From the similar geometries of the binding of EACA and AMCHA, it appears that the kon is an important component to the tighter binding of AMCHA to Klpg, as compared to EACA. Ordered solvation effects of the bound AMCHA may contribute to its longer lifetime on Klpg, thereby retarding koff, both effects thus accounting for the higher binding energy of AMCHA as compared to EACA.

Aminocaproic Acid↗
PubMedDate not supplied

[The effect of epsilon-aminocaproic acid on the normalization of embolizing fatty matter in the rabbit lung following experimental fractures. A polarized light study].

It has been confirmed that epsilon-aminocaproic acid (EACA), an inhibitor of fibrinolysis, reduced the incidence of fat embolism in the lung of rabbits with experimental bone fractures. Microscopic specimens of lungs, examined under polarized light, demonstrated the reduced amounts of lipoid materials that were prevalently undergraded. The action of the drug is owed to the inhibition of some primary mechanisms, involved in the genesis and diffusion of post-traumatic fat embolism.

Aminocaproates↗
PubMed1995

Fatal aortic thrombosis in a neonate during infusion of epsilon-aminocaproic acid.

Hemorrhagic complications are common in patients placed on extracorporeal life support (ECLS), especially in those who have additional risk factors. Several centers use epsilon-aminocaproic acid (EACA) in their high-risk ECLS patients in an attempt to decrease the incidence of such complications, despite the fact that no controlled trials have been performed examining the risks and benefits of its use. The authors report the case of a neonate who had fatal aortic thrombosis during EACA administration. Also included is a discussion of the use of EACA in patients who require cardiopulmonary bypass.

Abnormalities, Multiple↗
PubMed2002

The effect of epsilon aminocaproic acid on blood loss in patients who undergo primary total hip replacement: a pilot study.

OBJECTIVE: 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). DESIGN: A prospective, double-blind, randomized, controlled clinical trial. SETTING: A university-affiliated tertiary care hospital with a large joint arthroplasty population. PARTICIPANTS: Fifty-five patients who were scheduled for a primary THA. METHOD: 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. OUTCOME MEASURES: Blood loss from the start of surgery until the Hemovac drain was removed, and the transfusion rate and hemoglobin levels. RESULTS: 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. CONCLUSIONS: 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.

Aged↗
PubMed1987

Traumatic hyphema in children. Treatment with epsilon-aminocaproic acid.

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.

Adolescent↗
PubMed1985

Comparison of epsilon aminocaproic acid and normal saline for postoperative bladder irrigation following transurethral resection of prostate.

A prospective, randomized, double-blind trial of bladder irrigation with a 0.5% solution of epsilon aminocaproic acid (EACA) versus normal saline plus placebo was undertaken in 75 patients undergoing transurethral resection of the prostate for benign or malignant disease. Systemic absorption after irrigation with EACA was not detectable. No significant advantage, however, was demonstrated for the EACA solution over normal saline irrigation in measured postoperative blood loss, irrigant volume, hours of catheterization, or length of hospital stay.

Aminocaproates↗
PubMed1984

The mechanism of hepatoprotection by epsilon aminocaproic acid and putrescine.

Hepatic neutral serine proteases (including plasminogen activator) and ornithine decarboxylase (ODC) are induced by the hepatotoxin galactosamine (GALN). We examined the hepatoprotection conferred by epsilon-aminocaproic acid (EACA), a fibrinolytic inhibitor, putrescine (PUTR), the polyamine generated from ornithine by ODC, and alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC. GALN, 450 mg/kg, was administered intraperitoneally to Wistar-Lewis rats (group I). Groups II, III, and IV were also given EACA (80 mg/kg), PUTR (0.3 mmol/kg), or DFMO (0.3 mmol/kg), respectively, 1 hour before and 3, 7, and 12 hours after GALN. Rats were killed 2 hours after an intraperitoneal dose of 3H-thymidine was administered, 30 or 45 hours after GALN. EACA and PUTR were effective protectants against necrosis as judged by enzymes and histologic findings. Neither increased thymidine incorporation above the levels seen with GALN only. DFMO offered no protection even though thymidine incorporation at 45 hours was increased. Both EACA and PUTR, which have similar chemical structures, possessed significant antiprotease activity in vitro, suggesting that they act by inhibiting toxin-induced neutral serine protease activity and not by accelerating regeneration.

Aminocaproates↗
PubMed1984

Quantitative determination of plasma fibrinolytic activity in patients with ruptured intracranial aneurysms who are receiving epsilon-aminocaproic acid: relationship of possible complications of therapy to the degree of fibrinolytic inhibition.

Fifty-two patients were each given a constant infusion of 1.5 g of epsilon-aminocaproic acid (EACA) per hour after subarachnoid hemorrhage (SAH) from an intracranial aneurysm. Each patient's available plasminogen activity (APA), a measure of plasma fibrinolytic activity, was determined by fluorometric assay before and during EACA treatment. Five categories of potential EACA complications were identified: rebleeding, cerebral vasospasm, hydrocephalus, thrombosis, and miscellaneous (bleeding time prolongation, thrombocytopenia). The APA of the 37 patients with complications was significantly higher than that of the 15 without complications. Four patients suffered rebleeding episodes and had significantly higher APA levels during EACA therapy when compared to all other patients, i.e., those with and without other complications. Patients with vasospasm, hydrocephalus, and thrombotic complications also had significantly higher APA levels during EACA therapy compared to patients without complications. The latter may be simply a reflection of the activation of fibrinolytic activity that occurs after SAH. It is apparent from these studies that, after the initiation of EACA treatment, a maximal steady state inhibition of fibrinolytic activity is not achieved for 2 days and, after the cessation of EACA therapy, normal fibrinolytic activity is not restored for a period of 3 to 4 days. In addition, patients with thrombotic events may show persistently low serum plasminogen activity after discontinuance of EACA therapy, probably due to continuing thrombosis and consumption of plasminogen. These results indicate that patients with recurrent preoperative aneurysmal hemorrhage while on EACA therapy may have inadequate fibrinolytic inactivation, and this may be an important factor contributing to rebleeding episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2001

The Effect of epsilon-aminocaproic acid on perioperative blood loss in patients with idiopathic scoliosis undergoing posterior spinal fusion: a preliminary prospective study.

STUDY DESIGN: A prospective study evaluating the efficacy of epsilon-aminocaproic acid (EACA) in decreasing perioperative blood loss in idiopathic scoliosis. OBJECTIVES: To compare the perioperative blood loss and need for blood replacement in two groups of patients undergoing surgery for idiopathic scoliosis. One group received intraoperative EACA; the other did not and served as controls. SUMMARY OF BACKGROUND DATA: Excessive blood loss increases the operative time, risk for blood product disease transmission, postoperative complications, and costs associated with posterior spinal fusion and instrumentation. EACA is an antifibrinolytic agent that has been shown to be effective in reducing perioperative blood loss during pediatric cardiothoracic surgical procedures. We hypothesized that it would also be effective in lowering blood loss during posterior spinal fusion for idiopathic scoliosis. METHODS: We compared the perioperative blood loss of 28 consecutive pediatric patients with idiopathic scoliosis who underwent posterior spinal fusion and received intraoperative EACA with 31 consecutive patients who did not receive this medication and served as a control group. RESULTS: The patients in both groups were similar. Patients in the EACA group demonstrated statistically significant decreases in total estimated perioperative blood loss and the need for autologous blood transfusion. The patients in the EACA group had no intraoperative or postoperative complications related to the use of this medication. CONCLUSIONS: Based on these preliminary findings, we believe that EACA is helpful in decreasing blood loss in patients undergoing posterior spinal fusion and instrumentation, and may decrease the number of autologous units needed to maintain safe perioperative hemoglobin levels, thereby improving safety and lowering cost associated with scoliosis surgery.

Adolescent↗
PubMed1999

High anion gap metabolic acidosis associated with aminocaproic acid.

OBJECTIVE: To report a case of high anion gap metabolic acidosis related to infusion of aminocaproic acid (ACA) that temporarily corrected during hemodialysis and resolved upon ACA discontinuation. CASE SUMMARY: A 65-year-old white woman with staphylococcal sepsis complicated by acute renal failure was treated with ACA to control a hemorrhagic coagulopathy. After receiving an initial 5-g bolus of ACA, she received a continuous intravenous infusion of 500 mg/h for just over 5 days, then 250 mg/h for a final 12 hours. Immediately after beginning ACA therapy, she developed a severe anion gap metabolic acidosis that briefly improved after hemodialysis. The condition resolved completely only after the discontinuation of ACA and therapy with a systemic alkalinizer. DISCUSSION: ACA is not among the previously identified causes of high anion gap metabolic acidosis. The temporal profile relating anion gap to ACA initiation, hemodialysis treatment, and ACA discontinuation supports causality in this case. The magnitude of increase in the anion gap appears to have been proportional to the dose of ACA. CONCLUSIONS: In patients with renal impairment, ACA administration may produce a dose-related, high anion gap metabolic acidosis that might be reversible during hemodialysis. Insufficient data are available, but when ACA must be used in such patients, a more conservative dosing of ACA should be coupled with close monitoring.

Acid-Base Equilibrium↗
PubMed1988

Resistance of mice to reinfection after E-aminocaproic acid treatment of primary influenza virus infection.

The effect of proteolysis inhibitors on the formation of resistance to virus challenge has been studied in experimental influenza of mice. E-aminocaproic acid (E-ACA) when used in the treatment of influenza decreased the virus reproduction in lungs and also enhanced the humoral immune response. The antibody titre on days 14 to 21 post infection (p.i.) was significantly higher in the treated animals. On day 30 after challenge with the homologous strain (H3N2) the virus reproduced to low levels in the lungs of untreated convalescent mice, but no virus was detected in the lungs of mice which had been treated with E-ACA during primary infection. Marked increase of the antibody level was found in such mice. Upon challenge with lethal doses of the virulent strain (H1N1), the protection was significantly higher among animals treated with E-ACA during primary infection with a sublethal virus dose. We believe that the immunomodulatory action of E-ACA may play an important role in the increased resistance to challenge exhibited by such treatment.

Aminocaproates↗
PubMed2001

Epsilon-aminocaproic acid promotes the release of alpha2-antiplasmin during and after cardiopulmonary bypass.

This double-blind, randomized study compared the mechanisms by which low-dose aprotinin and epsilon-aminocaproic acid (EACA) inhibited fibrinolysis during cardiopulmonary bypass surgery. D-dimer levels during and after bypass were similar, indicating an equivalent inhibition of fibrinolysis. Effects on tissue plasminogen activator release were not associated with the inhibition of fibrinolysis by either drug. Treatment with EACA was associated with a substantial release of endogenous alpha2-antiplasmin, particularly 1 h after bypass. Compared with the aprotinin group, higher levels of the plasmin-alpha2-antiplasmin complex in the EACA group confirmed an increased inhibition of plasmin by alpha2-antiplasmin. In conclusion, it is hypothesized that EACA inhibited fibrinolysis by stimulating the release of the patients' own alpha2-antiplasmin.

Aminocaproic Acid↗
PubMed1988

Action of epsilon-aminocaproic acid on the proteolysis system during experimental influenza in mice.

Proteolysis system was examined in influenza-virus-infected mice after a 5-day course of therapeutic or preventive treatments with the proteolysis inhibitor epsilon-aminocaproic acid (E-ACA). The mice were infected with nonadapted influenza virus A/Hong Kong/1/68 (H3N2). E-ACA was shown to exert a pathogenetic action expressed by a marked tendency to normalization of elevated alkaline protease activity in damaged lung tissue and in the blood of infected animals. E-ACA induced a long-lasting high level activity of acidic proteases in the blood which correlated with increased protection of animals against influenza virus infection. It may be suggested that acidic proteases are involved in the preventive action of E-ACA and are a factor of resistance to virus infection.

Aminocaproates↗
PubMed1986

A comparison of two dose regimens of epsilon aminocaproic acid in the prevention and management of secondary traumatic hyphemas.

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).

Administration, Topical↗