The differences were particularly striking in samples taken 7 h or more after the administration of the thrombolytic agent. At hour 7, the level of cross-linked FDPs was 5,821 ±1,683 mg/ml in rt-PA-treated patients, compared with 2,924 ±1,186 mg/ml in strep-toldnase-treated patients (p<0.01). A marked and prolonged increase in FDPs in the late-drawn samples was observed after administration of rt-PA but not after streptokinase. This further demonstrates the existence of prolonged thrombolytic activity after rt-PA, despite its short half-life in the circulation. Preliminary clinical experience in patients with acute myocardial infarction seems to confirm that rt-PA infused as a bolus dose or with an accelerated regimen is at least as effective as, and probably more so than, rt-PA infused over a longer period.
The efficacy of bolus administration of rt-PA might be explained by a peculiar property of rt-PA. Studies in animal models showed that the thrombolytic effect of rt-PA persists beyond its time of clearance from the circulation. This sustained thrombolytic activity of rt-PA is presumably the consequence of its high affinity for fibrin. Plasminogen binds through its lysine-binding site to the t-PA—fibrin complex, where it is converted to plasmin. Plasmin formed on the fibrin surface has a longer half-life than that of circulating plasmin (10 s vs 0.1 s), probably because its lysine-binding site is protected from inactivation by 012-antiplasmin. Protection of fibrin-bound t-PA and plasmin from their specific inhibitors* could, therefore, explain the sustained thrombolytic activity of t-PA.