Thrombolytic therapies: the current state of affairs

Thrombotic occlusive diseases are manifested in several disorders that have significant morbidity and mortality, including acute myocardial infarction, pulmonary embolism, deep venous thrombosis, and cerebrovascular accidents. This review summarizes the recently published literature covering thrombolytic therapies in these diseases, with particular attention to comparisons between the fibrin-specific tissue plasminogen activators (alteplase, reteplase, and tenecteplase) and the nonfibrin-specific activators (streptokinase or urokinase plasminogen activator). These agents act to convert plasminogen to plasmin, which in turn cleaves fibrin as part of the lysis process. Fibrin-specific activators were anticipated to be more efficacious and safer than nonspecific agents in thrombolytic occlusive diseases because of their pathophysiologically restricted mechanism of action. However, the fibrin-specific activators also lyse physiological hemostatic plugs, which can result in costly adverse events. Efficacy of fibrin-specific tissue plasminogen activators has been shown to be generally equivalent, with similar mortality rates compared with nonspecific agents; however, fibrin-specific agents may be associated with an increased incidence of intracerebral hemorrhage and with increased costs. Therefore, it appears that given equivalent efficacy, nonfibrin-specific activators, such as streptokinase or urokinase, may be a safer choice in many thrombotic situations.