Historical overview of antithrombotic and thrombolytic therapy

Early attempts to treat thromboembolic disorders focused on the prevention of thrombus formation, along with the prevention of extension and/or embolization of an existing thrombus. Antithrombotic therapy for these conditions included intravenous and oral anticoagulants and later antiplatelet agents, all of which remain in use today. Subsequent research sought a thrombolytic agent that could lyse a clot directly. Intravenously administered streptokinase and urokinase were found to act on the inactive proenzyme plasminogen to produce the active enzyme plasmin that could safely and effectively lyse fresh fibrin clots. These agents have proved effective for the treatment of myocardial infarction and pulmonary embolism, as well as peripheral arterial and venous thromboembolic conditions. Recent efforts have been directed toward a search for clot-specific agents that would avoid the systemic lytic state associated with the use of urokinase and streptokinase. Three clot-specific plasminogen activators are currently being evaluated: recombinant tissue-specific plasminogen activator, anisoylated streptokinase plasminogen activator complex, and pro-urokinase.