Modification of venous stasis thrombosis in the rat by platelet-active drugs and by heparin.

In rats, stasis thrombosis of a renal vein was produced by the occlusion of a vascular segment after induction of systemic hypercoagulability by i.v. injection of ellagic acid. Prostaglandin E1, at doses which reduced platelet retention by glass beads (6 mug/min/300 g i.v.) only slightly reduced the thrombus size. The platelet release inhibitors suprofen and indomethacin, at doses which prolonged tail bleeding time in rats (50 mg/kg i.v.) had no effect on the thrombus size. Heparin (10 and 20 U/kg i.v.) produced a marked, dose-related reduction of venous thrombosis. The platelet-active compound VK774, at the dose levels of 50 to 10 mg/kg i.v., also reduced the thrombus size to about half that of controls. Lower doses (5, 2.5 mg/kg i.v.) had a progressively weaker effect. Binding to ellagic acid or induction of coagulation changes by VK774 are proposed as possible mechanisms of action. It is concluded that, in comparison with the contribution of plasma coagulation, the participation of the aspects of platelet function we measured in the development of venous stasis thrombosis is comparatively small.