Thrombolytic therapy in acute myocardial infarction - Comparison of procoagulant effects of streptokinase and alteplase regimens with focus on the kallikrein system and plasmin

Background-Thrombolytic therapy in patients with acute myocardial infarctio n (AMI) is hampered by procoagulant effects. In vitro studies have indicate d that plasmin stimulation activates the kallikrein-contact-phase system, r esulting in thrombin activation. This prospective comparative study was des igned to examine the procoagulant effects of streptokinase or alteplase in AMI. Methods and Results-Sixty-one patients with AMI received 1.5 million U of s treptokinase or front-loaded alteplase (up to 100 mg) and systemic heparin. Twenty-four patients with AMI and no thrombolytic therapy and 30 control s ubjects were examined for comparison. Molecular markers of thrombin, plasmi n activation, and coagulation activities were determined before therapy and serially for up to 10 days. Moderate thrombin (initial thrombin-antithromb in [TAT] complex 18+/-5 versus 4+/-0.3 mu g/L, P<0.05) and kallikrein (up t o 45+/-4 versus 30=/-1 U/L at 3 hours, P<0.01) activation occurs in patient s with AMI. D-Dimers are increased (P<0.01), and plasmin is stimulated (P<0 .01). Streptokinase and alteplase increase TAT to 50+/-17 and 51+/-18 mu g/ L at 3 hours and to 50+/-17 and 33+/-14 mu g/L at 6 hours, respectively (P< 0.01). Kallikrein activity is elevated (P<0.01) to 76+/-5 and 71+/-7 U/L at 3 hours and 64+/-6 and 47+/-5 U/L by streptokinase and alteplase, respecti vely, at 6 hours. Reductions in fibrinogen and increases in D-dimers and pl asmin-antiplasmin complexes are more marked (P<0.05 and 0.01) after strepto kinase versus alteplase. Correlations were found among TAT, kallikrein acti vity, and plasmin activation (P<0.01). Conclusions-The data indicate a more marked procoagulant action of the stre ptokinase regimen compared with front-loaded alteplase, thus supporting the hypothesis of a plasmin-mediated kallikrein activation with consecutive pr ocoagulant action in vivo.