Tissue plasminogen activator for the treatment of acute pulmonary embolism

Thirteen patients with acute pulmonary embolism were treated in a randomized double-blind fashion either with recombinant tissue plasminogen activator (rt-PA) 40 to 80 mg, usually in combination with heparin, or with placebo plus heparin. The drug was administered intravenously over 40 to 90 minutes. Nine patients received rt-PA, and four received placebo. A lytic effect was observed 1.5 and three hours after the onset of therapy with rt-PA based upon elevated levels of fragment-D dimers. Among the patients who received rt-PA, there was a modest improvement of the total pulmonary resistance 1.5 hours after the start of therapy, but the angiograms showed no significant changes in two hours. After 24 hours, the lung scans showed a trend toward greater improvement with rt-PA, but the rate of improvement in comparison to control subjects was not statistically significant. Massive bleeding occurred in one patient. The observations in this study suggest that rt-PA has little effect in two hours on angiographic clot burden, but may produce some improvement in hemodynamics. The treatment, however, is not without risk.