Fibrinolytic Therapy for Thromboembolic Diseases: Approved Indications and Future Directions

Fibrinolytic therapy plays a pivotal role in the management of thromboembolic diseases by promoting plasmin-mediated fibrin degradation and vessel recanalization, which frequently comes at the cost of increased risk of hemorrhagic events, including intracranial bleeding. Since the discovery of streptokinase in 1933, several additional fibrinolytic agents have been developed. Two plasminogen activators-urokinase and tissue plasminogen activator (tPA)-were identified in human samples. Through recombinant DNA technology, tPA was cloned and modified to produce alteplase. Subsequent efforts to prolong its plasma half-life led to the development of mutant derivatives such as tenecteplase and reteplase. Although fibrinolytic therapy in patients with ST-segment elevation myocardial infarction is currently restricted to those who cannot undergo primary percutaneous coronary intervention within 120 minutes of presentation, it has been a mainstay treatment for acute ischemic stroke and pulmonary embolism (PE) with hemodynamic compromise. Catheter-directed fibrinolysis has been evaluated in patients with intermediate-risk PE, deep vein thrombosis, acute limb ischemia, and after endovascular thrombectomy for ischemic stroke. Fibrinolytic agents have also been used in other clinically important indications, such as central venous access device thrombosis, mechanical prosthetic valve thrombosis, left ventricular assist device thrombosis, central retinal artery occlusion, cerebral venous sinus thrombosis, and left ventricular thrombus. This paper provides a comprehensive overview of the current applications, approved indications, evolving roles, and future directions of fibrinolytic agents in thromboembolic diseases.