Therapeutic plasma concentrations of epsilon aminocaproic acid and tranexamic acid in horses.

The study explores the concentration levels of particular antifibrinolytic drugs, epsilon aminocaproic acid (EACA) and tranexamic acid (TEA), needed to treat bleeding disorders in horses and suggests that current dosage schemes may be up to 20 times higher than necessary, leading to higher treatment costs and potential risk of adverse effects.

Approach and Methodology

The research used a combination of thromboelastography (TEG) and an in vitro model of hyperfibrinolysis, a condition that involves increased breakdown of blood clots, in order to estimate the therapeutic concentrations of the antifibrinolytic drugs for horses.

• The plasma was collected from 24 random source clinically healthy research horses, to which citrated (or anticoagulated) plasma was added. For comparison, commercial pooled human citrated plasma with normal coagulation parameters was purchased.
• The minimum concentration of the tissue plasminogen activator (tPA) that could induce complete fibrinolysis within 10 minutes was determined. This was done using serial dilutions of tPA in equine plasma.
• This data was then used to create an in vitro hyperfibrinolysis model with both equine and human citrated plasma.
• The minimum concentrations of EACA and TEA required to completely inhibit fibrinolysis for 30 minutes, described as estimated therapeutic concentrations, were determined using serial dilitions of the drugs.

Findings and Conclusion

The findings revealed that the therapeutic concentrations of EACA and TEA in horses were significantly lower than in humans. For EACA, the concentration was found to be between 3.77-7.86 μg/mL in horses which is much lower in comparison to 95.8-130.6 μg/mL in humans. Similar results were obtained for TEA, with concentrations ranging between 0.277-0.748 μg/mL in horses and 8.62-14.1 μg/mL in humans.

These findings led to the conclusion that the current dosing schemes for EACA and TEA may be substantially higher than necessary, as much as 20 times greater, which could not only escalate the cost of the treatment but also increase the risk of adverse effects. Consequently, the study advocates for revising current dosing schemes for horses and replacing them with amounts more reflective of the needs of the species.