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

摘要

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 g/mL to 500 g/mL and of TEA from 0 g/mL to 160 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 g/mL (95% confidence interval [CI], 433.2 to 590.3 g/mL) and 144.7 g/mL (95% CI, 125.2 to 164.2 g/mL), respectively. Concentrations of EACA and TEA necessary for complete inhibition of fibrinolysis in pooled human plasma were estimated as 122.0 g/mL (95% CI, 106.2 to 137.8 g/mL) and 14.7 g/mL (95% CI, 13.7 to 15.6 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.