Evaluation of tranexamic acid and ε-aminocaproic acid concentrations required to inhibit fibrinolysis in plasma of dogs and humans

Objective-To determine minimum plasma concentrations of the antifibrinolytic agents tranexamic acid (TEA) and epsilon-aminocaproic acid (EACA) needed to completely inhibit fibrinolysis in canine and human plasma after induction of hyperfibrinolysis. Samples-Pooled citrated plasma from 7 dogs and commercial pooled citrated human plasma. Procedures-Concentrations of EACA from 0 mu g/mL to 500 mu g/mL and of TEA from 0 mu g/mL to 160 mu g/mL were added to pooled citrated canine and human plasma. Hyperfibrinolysis was induced with 1,000 units of tissue plasminogen activator/mL, and kaolin-activated thromboelastography was performed in duplicate. The minimum concentrations required to completely inhibit fibrinolysis 30 minutes after maximum amplitude of the thromboelastography tracing occurred were determined. Results-Minimum plasma concentrations necessary for complete inhibition of fibrinolysis by EACA and TEA in pooled canine plasma were estimated as 511.7 mu g/mL (95% confidence interval [CI], 433.2 to 590.3 mu g/mL) and 144.7 mu g/mL (95% CI, 125.2 to 164.2 mu g/mL), respectively. Concentrations of EACA and TEA necessary for complete inhibition of fibrinolysis in pooled human plasma were estimated as 122.0 mu g/mL (95% CI, 106.2 to 137.8 mu g/mL) and 14.7 mu g/mL (95% CI, 13.7 to 15.6 mu g/mL), respectively. Conclusions and Clinical Relevance-Results supported the concept that dogs are hyperfibrinolytic, compared with humans. Higher doses of EACA and TEA may be required to fully inhibit fibrinolysis in dogs.