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

Am J Vet Res. 2014 Aug;75(8):731-8. doi: 10.2460/ajvr.75.8.731.

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.

MeSH terms

  • Aminocaproic Acid / blood
  • Aminocaproic Acid / pharmacology*
  • Animals
  • Antifibrinolytic Agents / blood
  • Antifibrinolytic Agents / pharmacology*
  • Dogs
  • Dose-Response Relationship, Drug
  • Fibrinolysis / drug effects*
  • Humans
  • Kaolin
  • Male
  • Plasma / chemistry
  • Species Specificity
  • Thrombelastography
  • Tranexamic Acid / blood
  • Tranexamic Acid / pharmacology*

Substances

  • Antifibrinolytic Agents
  • Kaolin
  • Tranexamic Acid
  • Aminocaproic Acid