Our study showed the efficacy of hirudin in inhibiting thrombus extension after rt-PA bolus. These results are consistent with the role of thrombin activity in thrombus extension after rt-PA. It has been shown that thrombolytic therapy is associated with thrombin generation, which could contribute to rethrombosis. Indeed, the activation of blood coagulation during thrombolytic therapy has already been reported. Alternatively, during the pharmacologic or mechanical dissolution of the thrombus, an active surface is produced, due to the exposure of thrombo-genic material; this surface appears to play an essential role in continued thrombosis during the lysis of the thrombus.
In association with lytic therapy, thrombin is exposed or generated on the thrombus surface. Whatever the mechanism of thrombus extension, our experimental studies confirm the importance of fibrin-bound thrombin in thrombus growth after thrombolysis. As an original finding, we observed that inhibition of fibrin-bound thrombin is crucial to optimization of thrombolysis with bolus rt-PA. Bolus rt-PA requires effective concomitant antithrombotic therapy to express its efficacy; r-hirudin and possibly other antithrombin Ill-independent thrombin inhibitors may be valuable adjuncts to bolus rt-PA therapy.