ϵ-Aminocaproic acid is a synthetic derivative of the amino acid lysine.1 The antifibrinolytic effect of EACA was first described in 19572; since then, EACA has been used frequently in humans to decrease the need for blood product administration (eg, during cardiopulmonary bypass procedures,3,4 prior to surgical intervention to treat subarachnoid hemorrhage,5 following dental extraction in hemophiliac patients,6 during extracorporeal membrane oxygenation in neonatal cardiac surgery,7 and during orthopedic and vertebral column surgery8). In horses, it has been suggested that EACA may be useful only in those with active hyperfibrinolysis,9 although in human medicine, EACA is thought to be effective even when bleeding is not associated with clinicopathologic signs of excessive hyperfibrinolysis.6
Inhibition of plasminogen activation by EACA results in altered clot maintenance without affecting clot formation. Kahn et al10 used modified whole blood clotting time as a measure of fibrinolytic activity and determined that EACA had an inhibitory effect on clot lysis in clinically normal humans. In an investigation of the mechanism of action of EACA by Thorsen,11 EACA decreased the adsorption of plasminogen to fibrin. Other researchers have investigated the effect of EACA on other factors involved in fibrinolysis, including α2-AP,12 FDPs, and D-dimers.4,13 However, the exact mechanism of action remains unclear.
The hemostatic process can be assessed by use of viscoelastic methods such as viscoelastic coagulation (sonoclot) analysisa or thromboelastography.14 Viscoelastic coagulation analysisa measures the impedance of movement of a small probe caused by clot development in a blood sample. This provides qualitative and quantitative information relating to the in vitro coagulation process, including fibrin formation, fibrin monomer polymerization, platelet interaction, clot retraction, and clot lysis. Results are displayed graphically, detailing clot signal over time. In humans, fibrinolysis occurs after the period of testing provided by viscoelastic coagulation analysis (ie, after 60 minutes)15; thus, fibrinolysis is generally not detected by use of that analyzer. However, in hyperfibrinolytic patients, the trace obtained from the analyzer changes in a characteristic way as clot strength decreases, and the degree of hyperfibrinolysis and the effects of treatment can be monitored with repeated use of the analyzer. Viscoelastic coagulation analysis provides dynamic information about the coagulation pathway and has advantages over traditional coagulation testing in clinical settings.14 In human medicine, viscoelastic coagulation analysis has been used to monitor coagulation in patients undergoing a variety of procedures, including cardiac surgery and transplant surgery, and is a useful predictor of postoperative bleeding after cardiopulmonary bypass.16 Viscoelastic coagulation analysis has been used to evaluate neonatal foals and is thought to be useful for assessment of platelet function and detection of coagulation abnormalities in neonates with sepsis.17
Anecdotally, EACA has been used by veterinarians to treat a variety of bleeding disorders in horses, including castration-associated hemorrhage, uterine artery hemorrhage, mycosis of the auditory tube diverticulum (guttural pouch), and intra-abdominal hemorrhage. At present, the efficacy of EACA has not been definitively determined, the therapeutic plasma drug concentration is unknown, and the pharmacokinetics of EACA in horses have not been elucidated. However, it is known that administration of EACA to horses results in alterations in PTT, plasma α2-AP activity, and plasma fibrinogen concentration.9 The purpose of the study reported here was to determine the pharmacokinetics and pharmacodynamics of EACA in healthy horses.
Fibrin degradation product
Partial thromboplastin time
Volume of distribution of the central compartment
Mean residence time
Area under the time-concentration curve (determined by the trapezoidal rule with extrapolation to infinity)
Sonoclot coagulation and platelet function analyzer, Sienco Inc, Arvada, Colo.
Angiocath, BD, Sandy, Utah.
Amicar, Hospira Inc, Lake Forest, Ill.
Saline solution, Hospira Inc, Lake Forest, Ill.
Heparin, Hospira Inc, Lake Forest, Ill.
Stachrom antiplasmin kit, provided by Diagnostica Stago, Parsippany, NJ.
ACL 7000, Instrumentation Laboratory, Lexington, Mass.
Thrombo-Wellcotest, Remel, Lenexa, Kan.
Advia 120, Bayer Health Care, Diagnostics Division, Tarrytown, NY.
SonOil Sienco Inc, Arvada, Colo.
Boomer, version 2.0, University of Oklahoma, Oklahoma City, Okla.
Instat, GraphPad Software Inc, San Diego, Calif.
Ririe DG, James RL, O'Brien JJ, et al. The pharmacokinetics of E-aminocaproic acid in children undergoing surgical repair of congenital heart defects. Anesth Analg 2002;94:44–49.
Frederiksen MC, Bowsher DJ, Ruo TI, et al. Kinetics of epsilonaminocaproic acid distribution, elimination, and antifibrinolytic effects in normal subjects. Clin Pharmacol Ther 1984;35:387–393.
Daily PO, Lamphere JA, Dembitsky WP. Effect of prophylactic epsilon-aminocaproic acid on blood loss and transfusion requirements in patients undergoing first-time coronary artery bypass grafting. J Thor Cardiovasc Surg 1994;108:1:99–104.
Eberle B, Mayer E, Hafner G, et al. High dose E-aminocaproic acid versus aprotonin: antifibrinolytic efficacy in first-time coronary operations. Ann Thorac Surg 1998;65:667–673.
Fish SS, Pancorbo S, Berkseth R. Pharmacokinetics of epsilon-aminocaproic acid during peritoneal dialysis. J Neurosurg 1981;54:736–739.
Downard CD, Betit P, Chang RW, et al. Impact of Amicar in hemorrhagic complications of ECMO: a ten year review. J Pediatr Surg 2003;38:1212–1216.
Florentino-Pineda I, Thompson GH, Poe-Kochert C, et al. The effect of Amicar on perioperative blood loss in idiopathic scoliosis: the results of a prospective, randomized double-blind study. Spine 2004;29:233–238.
Heidmann P, Tornquist SJ, Qu A, et al. Laboratory measure of hemostasis and fibrinolysis after intravenous administration of ϵ-aminocaproic acid in clinically normal horses and ponies. Am J Vet Res 2005;66:313–318.
Kahn MB, Palmer S, Marlar RA. A modified quantitative whole blood clot lysis method for general laboratory analysis of fibrinolysis. Thromb Res 1990;59:171–181.
Thorsen S. Differences in the binding to fibrin of native plasminogen and plasminogen modified by proteolytic degradation. Influence of E-aminocarboxylic acids. Biochem Biophys Acta 1975;393:55–65.
Ray MJ, Hales M, Marsh N. Epsilon-aminocaproic acid promotes the release of A2-antiplasmin during and after cardiopulmonary bypass. Blood Coagul Fibrinolysis 2001;12:129–135.
Slaughter TF, Faghih F, Greenberg CS, et al. The effects of epsilon-aminocaproic acid in fibrinolysis and thrombin generation during cardiac surgery. Anesth Analg 1997;85:1221–1226.
Sonoclot coagulation and platelet function analyzer with graphics printer operator's manual, Version 4.0, Arvada, Colo: Sienco Inc, 2–7.
Tuman KJ, McCarthy RJ, Ivankovich AD. Comparison of viscoelastic measures of coagulation after cardiopulmonary bypass. Anesth Analg 1989;69:69–75.
Dallap BL. Evaluation of hemostatic function in the equine critical care patient: old and new techniques, in Proceedings. 8th Annu Meet Int Vet Emerg Crit Care Soc 2002;625–629.
Quash T, Tippens M, Szlam F, et al. Quantitative assessment of fibrinogen cross-linking by E-aminocaproic acid in patients with end stage liver disease. Liver Transpl 2004;10:123–128.
Prasse KW, Allen D, Moore JN, et al. Evaluation of coagulation and fibrinolysis during the prodromal stages of carbohydrateinduced acute laminitis in horses. Am J Vet Res 1990;51:1950–1955.
Dallap B, Dolente B, Boston R. Coagulation profiles in 27 horses with large colon volvulus. J Vet Emerg Crit Care 2003;13:215–225.
Yamaoka K, Nakagawa T, Uno T. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm 1978;6:165–175.
Butterworth J, Robert L, Lin Y, et al. Pharmacokinetics of ϵ-aminocaproic acid in patients undergoing aortocoronary bypass surgery. Anesthesiology 1999;90:1624–1635.
Eisses MJ, Seidel K, Gabriel AS, et al. Reducing hemostatic activation during cardiopulmonary bypass: a combined approach. Anesth Analg 2004;98:1208–1216.
Manjunath G, Fozailoff A, Mitcheson D. Epsilon-aminocaproic acid and renal complications: case report and review of the literature. Clin Nephrol 2002;58:63–67.
Cooper RJ Jr, Abrams J, Frazier OH. Fatal pulmonary microthrombi during surgical therapy for end-stage heart failure: possible association with antifibrinolytic therapy. J Thorac Cardiovasc Surg 2006;131:963–968.
Ray M, Hatcher S, Whitehouse SL, et al. Aprotonin and epsilon aminocaproic acid are effective in reducing blood loss after primary total hip arthroplasty: a prospective randomized double-blind placebo–controlled study. J Thromb Haemost 2005;3:1421–1427.