Dynamic thrombosis and thrombolysis. Role of antithrombins.

In vivo thrombosis after deep arterial injury has been experimentally shown by receptor inhibitors to be mediated predominantly by thrombin activation of platelets and to a lesser extent by thrombin-related fibrin formation. Thrombosis and thrombolysis are dynamic and simultaneous processes that may influence each other, depending on the exposure and concentration of thrombin and administered agents and dosages. The dose-dependent antithrombotic effect of heparin is mediated by its antithrombin action, but is incomplete even at dosages of 500 units/kg administered over 1 hour.1"2 Because of the critical role of thrombin in the thrombotic and lytic processes and the improved inhibition of thrombin in all locations by small molecular and specific thrombin inhibitors, the articles concerning the specific thrombin inhibitors hirudin and argatroban in the previous3 and the present4 issues of Circulation are of interest. Haskel et al,3 in a recent issue of Circulation, compared single doses of antithrombin (hirudin and heparin) with antiplatelet (aspirin and antibody to glycoprotein 1Ib/IIIa platelet membrane receptor) therapy in the acceler-