Therapeutic Plasma Concentrations of Epsilon Aminocaproic Acid and Tranexamic Acid in Horses

Abstract

Background: 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.Hypothesis/Objectives: 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.Animals: Citrated plasma collected from 24 random source clinically healthy research horses. Commercial pooled human citrated plasma with normal coagulation parameters was purchased.Methods: 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.Results: Estimated therapeutic concentrations of EACA and TEA were significantly lower in horses (5.82; 95% CI 3.77-7.86 lg/mL and 0.512; 95% CI 0.277-0.748 lg/mL) than in humans (113.2; 95% CI 95.8-130.6 lg/mL and 11.4; 95% CI 8.62-14.1 lg/mL).Conclusions and Clinical Importance: Current dosing schemes for EACA and TEA in horses may be as much as 209 higher than necessary, potentially increasing cost of treatment and risk of adverse effects.

The Effects of Amicar and TXA on Lumbar Spine Fusion in an Animal Model

“…3 From a recent in vitro study the therapeutic dose of both TXA and Amicar was determined in both human and horse blood. 30 The estimated therapeutic concentrations were 113 μ g/mL for Amicar and 11 μ g/mL for TXA, translating to approximately 8 mg/kg and 0.8 mg/kg, respectively, for a subject of 72-kg body weight. These fi ndings were similar to a previous estimate, 31 and fall within the range used in this study even when the huge variation in resting metabolic rate between humans and mice is accounted for using described allometric physiological scaling.…”

Diagnosis, management and prognosis for haemoperitoneum in the horse

“…The use of fibrin stabilising drugs such as Aminocaproic acid have been used by many veterinarians instead of using whole blood transfusions (Heidmann et al 2005;Ross et al 2007;Fletcher et al 2013). Certainly if a whole blood transfusion is not an option, these drugs can be considered, but in the author's experience should not be used instead of whole blood.…”

Management of acute bleeding in a shetland pony during surgery for foreign body removal

“…Current doses for tranexamic acid in horses are anecdotal and not supported by pharmacokinetic studies, but dosage of 5–25 mg/kg intravenously is recommended by one Australian manufacturer for horses (Ilium Vasolamin S 100; Troy Laboratories, Glendenning, New South Wales, Australia). Horses are hypofibrinolytic compared with human beings, and in an in vitro study on therapeutic plasma concentrations of tranexamic acid in horses required to reverse hyperfibrinolysis induced with tissue plasminogen activator the minimum effective concentrations were 1/20 of those for human plasma 31. In this patient 500 mg of tranexamic acid (2.7 mg/kg) was used intravenously slowly via a peripheral intravenous catheter and another 500 mg was used topically around the incisional wound.…”