Evaluation of an oral direct factor Xa inhibitor anticoagulant in healthy adult horses

ObjectiveTo assess whether an oral direct factor Xa inhibitor (DiXaI) anticoagulant drug used at the low end of the recommended dose in people achieves presumed prophylactic plasma concentrations and does not induce bleeding in horses. DesignExperimental study. SettingField study. AnimalsTen healthy adult horses. InterventionsA DiXaI was administered at a dose of 0.125 mg/kg every 24 h orally for 4 days. Following a wash-out period of 2 weeks, 8 of 10 horses received daily subcutaneous doses of a low molecular weight heparin (dalteparin) for 4 consecutive days at 50 IU/kg. In both trials, antifactor Xa activity was measured at baseline time and 3 hours after each dose administration. Activated partial thromboplastin time, prothrombin time, hematocrit, erythrocyte agglutination, and platelet aggregation were monitored throughout the study. In addition, an in vitro spiking experiment was performed to demonstrate anticoagulant activity of this DiXaI in horse plasma. Main ResultsWhen treated with the DiXaI, this group of horses did not achieve the suggested thromboprophylactic plasma range of antifactor Xa activity (0.1-0.2 IU/mL), except for 1 horse after the first administration of the drug. In contrast, median values of plasma antifactor Xa activity 3 hours after receiving dalteparin were within the prophylactic range (0.16 IU/mL). No hemorrhagic events or erythrocyte agglutination were observed. In vitro addition of this DiXaI caused a concentration-dependent effect in antifactor Xa activity. ConclusionsAt the low end of the recommended dose in people this oral formulation of DiXaI did not reach prophylactic plasma antifactor Xa activity in this group of healthy adult horses. Further studies are warranted in order to establish the prophylactic dose for horses.