An Assay of the Antithrombotic Action of Warfarin: Its Correlation with the Inhibition of Stasis Thrombosis in Rabbits

Abstract

SummaryNo assay of the antithrombotic action of warfarin has been available. Experiments were performed to determine whether Xa inhibitory activity - the reaction rate between activated factor X (Xa) and antithrombin III - could serve this function. 105 warfarin-treated patients demonstrated a significant 18% increase in Xa inhibitory activity compared to 51 controls, p <0.001, without any correlation between this activity and the prothrombin times in the treated patients. A similar increase in Xa inhibitory activity was obtained in rabbits treated with 2 mg of warfarin per day compared to control animals, p <0.001. Employing an assay which routinely produced venous thrombosis after clotting proteases were infused into warfarin-treated and control rabbits, three observations were made. 1. The extent of stasis thrombosis induced by injection of thrombin, Xa or activated factor IX, was significantly reduced in warfarin-treated rabbits compared to control animals, independent of alteration in the four established vitamin K-dependent zymogens. 2. In the rabbit, significant changes in prothrombin times and prothrombin and factor X activities preceded by 5 days both the increase in Xa inhibitory activity and the antithrombotic effect which became significant on the sixth day. 3. The correlation between Xa inhibitory activity of warfarin-treated rabbits and the extent of stasis thrombosis induced by Xa was significant, p<0.05. Xa inhibitory activity is one measure of the antithrombotic action of warfarin.