This study was presented at the 2012 International Veterinary Emergency and Critical Care Symposium, San Antonio, TX
Therapeutic Plasma Concentrations of Epsilon Aminocaproic Acid and Tranexamic Acid in Horses
Article first published online: 1 OCT 2013
Copyright © 2013 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 27, Issue 6, pages 1589–1595, November/December 2013
How to Cite
Fletcher, D.J., Brainard, B.M., Epstein, K., Radcliffe, R. and Divers, T. (2013), Therapeutic Plasma Concentrations of Epsilon Aminocaproic Acid and Tranexamic Acid in Horses. Journal of Veterinary Internal Medicine, 27: 1589–1595. doi: 10.1111/jvim.12202
- Issue published online: 13 NOV 2013
- Article first published online: 1 OCT 2013
- Manuscript Accepted: 20 AUG 2013
- Manuscript Revised: 17 JUN 2013
- Manuscript Received: 3 APR 2013
- University of Georgia Equine Programs
- Bleeding disorders;
Antifibrinolytic drugs such as epsilon aminocaproic acid (EACA) and tranexamic acid (TEA) are used to treat various bleeding disorders in horses. Although horses are hypofibrinolytic compared to humans, dosing schemes have been derived from pharmacokinetic studies targeting plasma concentrations in humans.
We hypothesized therapeutic plasma concentrations of antifibrinolytic drugs in horses would be significantly lower than in humans. Our objective was to use thromboleastography (TEG) and an in vitro model of hyperfibrinolysis to predict therapeutic concentrations of EACA and TEA in horses and humans.
Citrated plasma collected from 24 random source clinically healthy research horses. Commercial pooled human citrated plasma with normal coagulation parameters was purchased.
Minimum tissue plasminogen activator (tPA) concentration to induce complete fibrinolysis within 10 minutes was determined using serial dilutions of tPA in equine plasma. Results used to create an in vitro hyperfibrinolysis model with equine and human citrated plasma, and the minimum concentrations of EACA and TEA required to completely inhibit fibrinolysis for 30 minutes (estimated therapeutic concentrations) determined using serial dilutions of the drugs.
Estimated therapeutic concentrations of EACA and TEA were significantly lower in horses (5.82; 95% CI 3.77–7.86 μg/mL and 0.512; 95% CI 0.277–0.748 μg/mL) than in humans (113.2; 95% CI 95.8–130.6 μg/mL and 11.4; 95% CI 8.62–14.1 μg/mL).
Conclusions and Clinical Importance
Current dosing schemes for EACA and TEA in horses may be as much as 20× higher than necessary, potentially increasing cost of treatment and risk of adverse effects.