Low dose urokinase preactivated natural prourokinase for thrombolysis in acute myocardial infarction.

By inducing minimal free-fibrinolytic activity with low dose urokinase, the lag phase of prourokinase can be overcome, and the rate of thrombolysis with this substance can be strongly enhanced. The thrombolytic potency of a combination of 250,000 IU of urokinase and 2 doses of prourokinase (4.5 or 6.5 megaunits) was evaluated in an open-label, nonrandomized dose-finding study. Thirty-one patients participated. With 4.5 megaunits of prourokinase (group 1, 15 patients) patency was demonstrated angiographically at 60 minutes in 33% while with 6.5 megaunits (group II, 16 patients) 75% patency was achieved (p less than 0.01). A second angiogram recorded 24 to 36 hours after thrombolysis revealed reocclusion in 60 versus 8% of primarily patent coronary arteries (p less than 0.05). Hemostatic monitoring in both groups revealed only slight to moderate consumption of fibrinogen (-9 vs -13%), plasminogen (-29 vs -34%) and alpha 2-antiplasmin (-59 vs -63%), and an increase in D-dimers, the split products of cross-linked fibrin, to a maximum of 1.008 +/- 1.211 vs 0.547 +/- 0.684 micrograms/liter. None of these differences was significant. Bleeding complications were more frequently observed in group II (13 vs 37%) (difference not significant), but were mild and related to puncture sites, except in 1 patient with mild oozing from the gum. No major hemorrhage was observed. These results suggest that low dose urokinase preactivation enhances the thrombolytic potency of prourokinase, without affecting its high fibrin specificity. Compared to previous studies using only prourokinase, low dose urokinase preactivation reduces by 50% the prourokinase dose as required for effective thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)