Beyond thrombolysis: other effects of thrombolytic drugs

OBJECTIVE: To review the effects of plasminogen activators (tissue plasminogen activator, streptokinase, and anistreplase) on fibrinogen and thrombin, platelets, complement, blood rheology, and neutrophils. DATA SOURCES: A MEDLINE search, as well as a review of recent scientific abstracts, was conducted to identify pertinent literature. STUDY SELECTION: Focus was placed on studies conducted in humans. However, many in vitro studies have been performed to fully elucidate the effect of plasminogen activators on different aspects of hemostasis and on the fibrinolytic and immune systems. DATA EXTRACTION: Data from in vitro, human, and animal studies were evaluated. DATA SYNTHESIS: There is a discrepancy between 90-minute patency and mortality in acute myocardial infarction patients treated with thrombolytic drugs. This could be caused, in part, by other hematologic and immunologic effects of thrombolytic drugs. Though the emphasis of clinical trials has been infarct-related artery patency, left ventricular function, and mortality, some studies have evaluated the effect of thrombolytic agents on fibrinogen and thrombin, platelets, blood rheology, complement, and neutrophils. This review discusses the alteration of systemic hematologic and immunologic parameters by thrombolytic drugs and the possible clinical implications of these effects. CONCLUSIONS: Although the interactions between thrombolytic drugs, hemostasis, and the fibrinolytic and immune systems are complex and still not fully understood, it appears that these drugs differ in their effects on these systems. A greater understanding of these properties and their clinical implications may ultimately enhance the care and outcome of acute myocardial infarction patients treated with thrombolytic therapy.