Activation of the complement system by recombinant tissue plasminogen activator

Abstract

Recent trials have shown that recombinant tissue plasminogen activator (rt-PA) is an effective thrombolytic agent in patients with acute myocardial infarction. Because rt-PA converts plasminogen to plasmin, which is known to activate complement in vitro, we tested the hypothesis that rt-PA can induce in vivo activation of complement. Studies were performed in 12 patients with acute myocardial infarction. Six control patients had patent coronary arteries and did not receive rt-PA; these patients had normal values of the components of the complement system C4a (409 +/- 111 ng/ml) and C5a (8.8 +/- 1.8 ng/ml) with a slight elevation of C3a (204 +/- 6.6 ng/ml) in samples collected before coronary arteriography (253 +/- 25 minutes after onset of pain). After coronary arteriography, there was a slight decrease in the values of C4a (224 +/- 37 ng/ml), C5a (7.3 +/- 1.3 ng/ml) and C3a (164 +/- 35 ng/ml). The remaining six patients had complete coronary occlusion and received rt-PA (80 to 150 mg intravenously). In this treated group, before coronary arteriography the values of C4a (406 +/- 51.6 ng/ml) and C5a (8.1 +/- 1.9 ng/ml) were normal, and those of C3a were slightly elevated (250 +/- 76 ng/ml). All complement values obtained before rt-PA were similar to those in the untreated group. However, after administration of rt-PA (but before any angiographically detectable reperfusion), there was a striking increase in C4a (2,265 +/- 480 ng/ml; p less than 0.01), C3a (600 +/- 89 ng/ml; p less than 0.05) and C5a (30.0 +/- 4.5 ng/ml; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)