Epsilon-aminocaproic acid inhibition of fibrinolysis in vitro: should the 'therapeutic' concentration be reconsidered?
The therapeutic concentration of epsilon-aminocaproic acid (EACA) has been 130 microg/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 microg/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 microg/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 microg/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.
Nielsen
Vance G
VG
Department of Anesthesiology, The University of Alabama, Birmingham, Alabama, USA. vnielsen@uab.edu
Cankovic
Lana
L
Steenwyk
Brad L
BL
D015119:Aminocaproic Acid / Q000592:standards* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D010949:Plasma / Q000502:physiology; D012015:Reference Standards; D013916:Thrombelastography; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D010959:Tissue Plasminogen Activator; D015119:Aminocaproic Acid