Gewebeplasminogenaktivatoren

Gewebeplaminogenaktivator, commonly abbreviated tPA, is a serine protease that activates plasminogen to plasmin, initiating fibrinolysis and the breakdown of fibrin clots. It is produced by endothelial cells and used clinically in recombinant forms as tissue-type plasminogen activators. The most widely used is alteplase (recombinant rt-PA). Other tPAs include reteplase and tenecteplase, which differ in pharmacokinetics and dosing.

Mechanism of action: tPA binds to fibrin within a thrombus and accelerates the conversion of plasminogen to plasmin on the clot surface. Plasmin then degrades fibrin and other clot-associated proteins, leading to dissolution of the clot. The clot-specific activation reduces systemic plasmin generation compared with non-fibrin-targeted activators, but systemic bleeding remains a potential risk.

Clinical use: rt-PA is employed in the treatment of acute ischemic stroke within defined time windows, and in selected cases of myocardial infarction or massive pulmonary embolism where reperfusion therapy is indicated and no contraindications exist. Its use requires rapid assessment and careful risk–benefit evaluation.

Administration and safety: tPA is given intravenously, with dosing tailored to the indication. It has a short half-life and is typically monitored to balance clot dissolution against bleeding risk. Major safety concerns include intracranial hemorrhage and other major bleeding. Contraindications encompass active internal bleeding, recent intracranial surgery or hemorrhagic stroke, known intracranial vascular lesions, uncontrolled hypertension, and certain recent surgeries or injuries. Careful patient selection and monitoring are essential to minimize complications.