The anticoagulant, antithrombotic and haemorrhagic effect of long-term warfarin on experimental venous and arterial thrombosis in the rat.

The amount of thrombus formed in one hour, on standard platinum wire in aorta and vena cava of 48 control and 96 warfarin treated rats of both sexes, was measured. Warfarin was given in varying doses (0.1-0.18 mg/kg) for ten consecutive days before operation to enable the coagulation factors to stabilize. Factors II, VII and X levels as well as prothrombin time (PT) values were obtained for each animal. Factor levels and PT ratio were related to reduction in arterial and venous thrombus weight. The relation between reduction in thrombus weight and depletion in coagulation factor levels was best for factor II and fairly good for factor X at all levels of anticoagulation. All animals which were haemorrhagic had factor II levels of below 15%, with a mean of 8%. At low warfarin dosage a significant reduction of thrombus (> 30%) went undetected by any test, but was least frequently undetected by factor II and most frequently undetected by PT. All rats with diminished thrombus had at least one factor depleted. Haemorrhagic animals were found with any PT ratio in excess of unity. Factor II reflected antithrombotic and haemorrhagic effects of warfarin much better than factors X, VII, or PT.