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Serial coagulation studies were obtained in 25 patients treated with intracoronary streptokinase infusion for myocardial infarction (23 patients) or coronary insufficiency (two patients) to determine the frequency of systemic fibrinolytic activity. Clotting studies were obtained before and after infusion and at 4-hour intervals until normalization. Intracoronary thrombolysis was successful in 20 of 23 patients (87%) with myocardial infarction. Streptokinase dosage in this study was 201,000 +/- 74,000 IU (+/- SD). Systemic fibrinolytic activity, defined as greater than 70% reduction of fibrinogen using a functional assay (Claus method), occurred in 22 of 25 patients (88%) and was present at a mean streptokinase dosage of 119,000 +/- 52,000 IU. Fibrinogen in the total population decreased from 342 +/- 80 to 87 +/- 94 mg% (p less than 0.0001). In patients with systemic effect, the mean fibrinogen level after infusion was 17% of baseline, increased to 43% at 24 hours, and returned to normal at 30 hours. Plasminogen decreased to 7% of baseline activity after infusion (p less than 0.0001), was 44% of baseline at 24 hours, and returned to normal at 48 hours. Intraprocedural sampling during infusion showed reduction of fibrinogen by 25% after 30,000 IU (p less than 0.0005) and by 71% at 120,000 IU (p less than 0.0001); plasminogen decreased by 50% after 30,000 IU (p less than 0.0001) and by 84% at 120,000 IU (p less than 0.0001). Prothrombin time increased from 11.5 +/- 0.8 seconds to 22.0 +/- 7.8 seconds after infusion (p less than 0.0001) and returned to normal at a mean of 18 +/- 11 hours after infusion. Partial thromboplastin time was markedly prolonged (greater than 100 seconds) after infusion, returned to less than or equal to 2 times control at 5 +/- 2 hours, and returned to normal at 9 +/- 4 hours after infusion. Fibrinogen degradation products were less than 10 micrograms/ml before infusion, increased to greater than 40 micrograms/ml after infusion, and remained greater than 40 micrograms/ml in 40% of patients at 24 hours after infusion. These data indicate that systemic fibrinolytic activity occurs in a high percentage of patients with "low-dose" intracoronary streptokinase infusion and that coagulation variables may be altered for 24-48 hours after infusion.