Comparative study on the antithrombotic effects of a synthetic thrombin inhibitor and of heparin in animal models.

The antithrombotic effects of the synthetic thrombin inhibitor 4-amidinophenylpyruvic acid and the naturally occurring thrombin inhibitor heparin were studied in a stasis-induced venous thrombosis model and an extracorporeal shunt model in rats. The incidence of venous thrombosis was reduced in a dose-dependent manner by both inhibitors. Thrombus size was reduced in the animals in which thrombi continued to form under treatment. The antithrombotic effect of the synthetic inhibitor was accompanied by considerable prolongation of the plasma thrombin time, whereas the effect of heparin on the thrombin time was less pronounced. The time until thrombotic occlusion of the extracorporeal arterio-venous shunt occurred was prolonged by both inhibitors in dependence upon the dose. The amount of thrombotic occluding material in the shunt was reduced and altered in composition. Synthetic thrombin inhibitors are potential antithrombotic agents whose effectivity corresponds to that of heparin.