Dose-dependent antithrombotic effect of warfarin in rabbits

One-hundred and fifty-one rabbits, divided into controls and animals treated with varying daily doses of warfarin, were subjected to the stasis assay, and the amount of thrombosis quantitated after intravascular coagulation was initiated either by activated factor X or tissue thromboplastin. Following 8-10 days of warfarin administration, there was a significant dose-dependent decrease in the vitamin-K-dependent coagulation factors paralleled by an increase in the prothrombin time ratio. Whether thrombosis was initiated by activated factor X or tissue thromboplastin, there was, with increasing drug dose, a progressive increase in the inhibition of stasis thrombosis. This significant antithrombotic effect occurred even when the vitamin-K-dependent coagulation activities were at a mean value of 50%.