Thus, reducing thrombus size requires a favorable net balance between lysis of fibrin and accretion of new fibrin on the thrombus. As these 2 processes appear to be concomitant more than sequential, a favorable balance will positively influence the lysis of the thrombus, in addition to reducing the risk of its reextension after thrombolysis.
The short plasma half-life of rt-PA is considered a potential limitation because of possible inability to lyse new fibrin accreted on thrombi and resultant thrombus reextension after thrombolysis. This limitation might be particularly relevant for the administration of rt-PA over a short period of time. To test this hypothesis, we performed a series of consecutive studies in rabbits. The studies were first aimed at evaluating the relative roles of lysis of preformed fibrin and accretion of new fibrin on the thrombi in determining the final size of venous thrombi after bolus rt-PA administration. We then explored 2 strategies to prevent thrombus growth after bolus rt-PA: the infusion of heparin and hirudin with bolus rt-PA, and the bolus injection of a hybrid plasminogen activator with prolonged half-life.