Antithrombotic and haemorrhagic effects of synthetic and naturally occurring thrombin inhibitors.

The effects of the synthetic thrombin inhibitor N alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide (beta Nas-Gly-(pAm)Phe-Pip) and the naturally occurring inhibitors hirudin and heparin on the bleeding time were studied in mice and rats by the method of transection of the tail tip and of standardized incision of the tail. With both methods the thrombin inhibitors prolonged the bleeding time in dependence on the dose and the plasma concentration obtained. The transection bleeding time was influenced by the inhibitors in a similar manner, whereas in the case of incision of the tail heparin caused a more pronounced effect than hirudin and beta Nas-Gly-(pAm)Phe-Pip. Comparison of the antithrombotic actions of the inhibitors with their effects on the bleeding time showed that, in contrast to the selective thrombin inhibitors hirudin and beta Nas-Gly-(pAm) Phe-Pip, antithrombotically effective doses of heparin induced a clear prolongation of bleeding time.