urokinase

Urokinase (urokinase-type plasminogen activator, uPA) is a serine protease originally isolated from human urine, produced by the kidneys and various other tissues including endothelial cells. Mechanistically, it cleaves the Arg560-Val561 bond in plasminogen, converting it to plasmin, which then degrades fibrin clots into fibrin degradation products (including D-dimer). Unlike streptokinase, urokinase acts directly on plasminogen without forming an activator complex, and unlike tPA, it does not preferentially activate fibrin-bound plasminogen, making it less fibrin-specific and associated with more systemic fibrinolytic effects (i.e., more risk of systemic bleeding). Clinically, urokinase has been used for thrombolysis in conditions such as pulmonary embolism, catheter-directed thrombolysis for deep vein thrombosis, clearing occluded catheters, and historically for acute myocardial infarction (before tPA/alteplase became standard). It has a short half-life and requires continuous infusion. Contraindications mirror those of other thrombolytics: active internal bleeding, recent surgery, history of hemorrhagic stroke, and severe hypertension. Adverse effects include bleeding complications, especially intracranial hemorrhage. On USMLE, urokinase is often tested in comparison to other thrombolytics: streptokinase (bacterial, antigenic, forms complex with plasminogen), alteplase/tPA (fibrin-specific, recombinant), and tenecteplase/reteplase (longer-acting tPA variants). Understanding the fibrinolytic pathway and plasminogen activators is essential for both pharmacology and coagulation cascade topics.