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

Daniel J. FletcherDepartment of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

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Kelly J. BlackstockDepartment of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

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Kira EpsteinDepartment of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Benjamin M. BrainardDepartment of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Abstract

Objective—To determine minimum plasma concentrations of the antifibrinolytic agents tranexamic acid (TEA) and ϵ-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 μg/mL to 500 μg/mL and of TEA from 0 μg/mL to 160 μg/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 μg/mL (95% confidence interval [CI], 433.2 to 590.3 μg/mL) and 144.7 μg/mL (95% CI, 125.2 to 164.2 μg/mL), respectively. Concentrations of EACA and TEA necessary for complete inhibition of fibrinolysis in pooled human plasma were estimated as 122.0 μg/mL (95% CI, 106.2 to 137.8 μg/mL) and 14.7 μg/mL (95% CI, 13.7 to 15.6 μg/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.

Abstract

Objective—To determine minimum plasma concentrations of the antifibrinolytic agents tranexamic acid (TEA) and ϵ-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 μg/mL to 500 μg/mL and of TEA from 0 μg/mL to 160 μg/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 μg/mL (95% confidence interval [CI], 433.2 to 590.3 μg/mL) and 144.7 μg/mL (95% CI, 125.2 to 164.2 μg/mL), respectively. Concentrations of EACA and TEA necessary for complete inhibition of fibrinolysis in pooled human plasma were estimated as 122.0 μg/mL (95% CI, 106.2 to 137.8 μg/mL) and 14.7 μg/mL (95% CI, 13.7 to 15.6 μg/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.

Contributor Notes

Dr. Blackstock's present address is Fifth Avenue Veterinary Specialists, 1 West 15th St, New York, NY 10011.

Presented in abstract form at the International Veterinary Emergency and Critical Care Symposium, Nashville, Tenn, September 25, 2011.

Address correspondence to Dr. Fletcher (djf42@cornell.edu).