The complement system is activated by streptokinase, but not by combined heparin-recombinant tissue-type plasminogen activator therapy in patients with myocardial infarction: A placebo-controlled study

Based on previous observations, we hypothesized that thrombolytic therapy for patients with myocardial infarction causes an activation of the complement system in vivo. In our present placebo-controlled study in patients with myocardial infarction treated with 100 mg recombinant tissue-type plasminogen activator (rt-PA) (n=20) or 1,500,000 U of streptokinase (n=7), we assessed plasma concentrations of plasminogen and complement components C1, C1-esterase inhibitor, and the activation product C3d to elucidate activation of the complement pathways. We observed that rt-PA treatment activates significantly less plasminogen in the circulation (about 50%) when compared with streptokinase therapy (> 95%) (P < 0.001). The complement system was not significantly affected by rt-PA treatment, whereas streptokinase therapy caused a marked selective increase of C3d in plasma to significantly higher median concentrations (38.0 mU/L, P<0.01) when compared with patients treated with rt-PA (24 mU/L) or placebo (26 mU/L). Test tube experiments revealed that plasmin does not activate the complement system, whereas the streptokinase-plasminogen complex has a pronounced capacity to do so. We conclude that coronary thrombolysis with streptokinase activates the complement system in vivo, and that this effect is related to the capacity of the streptokinase-plasminogen complex. It is suggested that the pronounced activation of complement induces systemic effects in streptokinase-treated patients, notably an accelerated activation of coagulation.