Protective effect of warfarin in arterial thrombosis: evidence from a vascular prosthesis model in rats

Three different schedules of treatment with warfarin were studied in rats bearing a polyethylene cannula in their abdominal aorta. The time of occlusion of the vascular prosthesis was significantly prolonged when warfarin was started 24 hr previously, at the time of loop insertion or 24 hr later. When the drug treatment was started 24 hr before insertion of the loop, however, a high degree of toxicity was observed. The animals of this group that died of hemorrhage had significantly lower mean thrombotest levels. On the other hand, the correlation between occlusion of the loop and level of anticoagulation was not as simple as one might anticipate; on the one hand, severe anticoagulation did not protect all of the rats from loop occlusion, but, on the other hand, recovery from hypocoagulability was not always immediately followed by occlusion of the loop. In order to better elucidate the mechanism of the antithrombotic effect of warfarin, we also assessed the effect of the drug on platelet-vessel wall interaction by the template bleeding time. A close association existed between warfarin-induced hypocoagulability and prolongation of the bleeding time. These observations may constitute the experimental basis for a better understanding of the antithrombotic effect of warfarin in some arterial diseases and in myocardial infarction.