Study of Thrombolytic Effects of Bolus
Injection of a Plasminogen Activator with Prolonged Half-life.
The short half-life of rt-PA might be a possible limitation for its bolus administration due to its inability to prevent the accretion of new fibrin on the thrombi and thus thrombus extension. In recent years, several forms of mutants and hybrids of plasminogen activators have been developed. One of the major aims of producing these third-generation plasminogen activators was to prolong the plasma half-life of rt-PA. Kgtu-PA (CGP 42935, Ciba-Geigy) is a hybrid plasminogen activator linking the kringle-2 domain of rt-PA to the catalytic protease domain of scu-PA. K2tu-PA has a high specific activity, retains the property of being activated by fibrin, and has a plasma half-life of over 30 min. The aim of this study was to evaluate the accretion of new fibrin on preexisting thrombi after a bolus of t-PA and Katu-PA.
Thrombus growth was evaluated as previously described in this article. Boluses of rt-PA and K*tu-PA were injected at the dose of 0.4 mg/kg. This dose was selected because it was known from previous studies to produce 40% thrombolysis when injected as a bolus. The accretion of radioactive fibrin on the thrombi was assessed 3 h after rt-PA or K*tu-PA bolus. No concomitant adjunctive treatment was administered.