An assay of the antithrombotic action of warfarin: its correlation with the inhibition of stasis thrombosis in rabbits

S. Wessler, S. N. Gitel, H. Bank, U. Martinowitz, R. C. Stephenson

Research output: Contribution to journalArticlepeer-review

Abstract

No assay of antithrombotic action of warfarin has been available. Experiments were performed to determine whether Xa inhibitors 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 wafarin 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.

Original languageEnglish
Pages (from-to)486-498
Number of pages13
JournalUnknown Journal
Volume40
Issue number3
DOIs
StatePublished - 1979

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