Hirudin is a potent and highly specific thrombin inhibitor able to prevent thrombus growth in rabbits when given in combination with a prolonged infusion of rt-PA. The biologic rationale for the pharmacologic efficacy of hirudin is provided by recent achievements in the basic knowledge of the process of thrombus extension during and after thrombolysis.
Although the mechanisms contributing to rethrombosis after thrombolytic therapy have not been completely elucidated, increasing attention has been drawn to the possible role of thrombus-bound thrombin. Thrombin incorporated in the thrombus is in an active form. It has recently been shown that rt-PA, removing successive fibrin layers, exposes inaccessible molecules of active thrombin on the surface of the residual thrombus. Unlike plasma free thrombin, thrombin bound to fibrin is poorly accessible to heparin-antithrombin III complex. Thus, the fibrin-bound thrombin remains active and favors rethrombosis. Hirudin is active against both free circulating thrombin and thrombus-bound thrombin.
We have performed further experimental studies in rabbits to evaluate the efficacy of heparin and hirudin in preventing thrombus extension after a bolus of rt-PA.
Study of Effects on Heparin and r-Hirudin in Preventing Accretion of New Fibrin on Thrombi after rt-PA Bolus