The therapeutic concentration of ε-aminocaproic acid (EACA) has been 130 μg/ml or greater for nearly 50 years. We tested the effects on clot growth/disintegration of EACA with a plasmatic model of hyperfibrinolysis in vitro. Human plasma was exposed to 1000 U/ml tissue-type plasminogen activator containing 0, 13, 65 or 130 μg/ml EACA, with clot growth/disintegration kinetics quantified via thrombelastography. Data were analyzed with one-way analysis of variance or Kruskal–Wallis analysis of variance as appropriate. Exposure of plasma to 1000 U/ml tissue-type plasminogen activator resulted in a brief-lived clot, lasting 2 min. EACA at all concentrations tested significantly increased the rate of clot growth compared with samples with 0 μg/ml EACA. Clot strength was significantly increased by EACA in a concentration-dependent fashion. Similarly, EACA significantly prolonged the time of onset of clot lysis and decreased the rate of lysis. Samples with 130 μg/ml EACA had no sign of lysis present for 30 min. Subtherapeutic to therapeutic concentrations of EACA significantly attenuated or abolished fibrinolysis in the presence of a concentration of tissue-type plasminogen activator more than 2000-fold that encountered systemically during cardiopulmonary bypass. Further clinical investigation is warranted to determine whether smaller concentrations of EACA could provide a reduction in bleeding with a concomitant decrease in thrombotic complications.
Department of Anesthesiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
Received 6 June, 2006
Revised 23 August, 2006
Accepted 7 September, 2006
Correspondence and requests for reprints to Vance G. Nielsen, MD, Department of Anesthesiology, The University of Alabama at Birmingham, 901 South 19th Street, Basic Medical Research II, Room 206, Birmingham, AL 35249-6810, USA Tel: +1 205 934 4696; fax: +1 205 934 7437; e-mail: firstname.lastname@example.org
Sponsorship: This investigation was supported by the Department of Anesthesiology.