Thrombolytic Therapy in Acute Myocardial Infarction

Abstract

Background-Thrombolytic therapy in patients with acute myocardial infarction (AMI) is hampered by procoagulant effects. In vitro studies have indicated that plasmin stimulation activates the kallikrein-contact-phase system, resulting in thrombin activation. This prospective comparative study was designed 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 streptokinase or front-loaded alteplase (up to 100 mg) and systemic heparin. Twenty-four patients with AMI and no thrombolytic therapy and 30 control subjects were examined for comparison. Molecular markers of thrombin, plasmin activation, and coagulation activities were determined before therapy and serially for up to 10 days. Streptokinase and alteplase increase TAT to 50Ϯ17 and 51Ϯ18 g/L at 3 hours and to 50Ϯ17 and 33Ϯ14 g/L at 6 hours, respectively (PϽ0.01). Kallikrein activity is elevated (PϽ0.01) to 76Ϯ5 and 71Ϯ7 U/L at 3 hours and 64Ϯ6 and 47Ϯ5 U/L by streptokinase and alteplase, respectively, at 6 hours. Reductions in fibrinogen and increases in D-dimers and plasmin-antiplasmin complexes are more marked (PϽ0.05 and 0.01) after streptokinase versus alteplase. Correlations were found among TAT, kallikrein activity, and plasmin activation (PϽ0.01). Conclusions-The data indicate a more marked procoagulant action of the streptokinase regimen compared with front-loaded alteplase, thus supporting the hypothesis of a plasmin-mediated kallikrein activation with consecutive procoagulant action in vivo.

Microvascular Thrombosis, Fibrinolysis, Ischemic Injury, and Death After Cerebral Thromboembolism Are Affected by Levels of Circulating α2-Antiplasmin

“…Chopp and colleagues postulated that inhibition of fibrinolysis may accentuate microvascular thrombosis in stroke and studies have shown that microvascular thrombosis induced by endotoxemia is enhanced when fibrinolysis is inhibited. 24, 44-46 Consistent with that hypothesis, our data shows that differences in a2AP levels, which affect dissolution of the MCA thrombus, also modulate the development of microvascular thrombosis. Still, it is important to note that, despite their common effects on promoting thrombus dissolution through plasmin, TPA accentuated, while a2AP-I diminished, microvascular thrombosis.…”

A pilot study of streptokinase‐induced endothelial injury and platelet activation following acute myocardial infarction

“…In contrast, the rapid rise in sTM following initiation of streptokinase is temporarily associated with a fall in vitamin E. These changes support the hypothesis that increased oxidative stress during reperfusion is associated with endothelial damage, and this may have important prognostic implications [4]. The fall in fibrinogen is so immediate and profound that it is likely to be directly or indirectly due to the streptokinase, which is also associated with increased levels of the fibrin degradation product, d ‐dimer [5]. The observed platelet activation (increased sPsel) following both AMI and thrombolysis occurred despite routine administration of aspirin (acetylsalicylic acid) 300 mg.…”

Plasma kallikrein mediates brain hemorrhage and edema caused by tissue plasminogen activator therapy in mice after stroke

“…36 Systemic activation of the KKS by tPA could have both peripheral and cerebral effects. Peripheral activation of PKal by tPA could contribute to orolingual angioedema that has been reported to occur at an incidence of up to 5% of cases during thrombolytic For personal use only.…”