alteplase

Alteplase is a serine protease that activates plasminogen to plasmin, which degrades fibrin clots (fibrinolysis). It preferentially activates plasminogen bound to fibrin, giving it relative clot-selectivity compared to older agents like streptokinase, though systemic fibrinolysis and bleeding risk still occur.

Clinical uses: - Acute ischemic stroke: must be given within 3-4.5 hours of symptom onset (per specific eligibility criteria) after excluding hemorrhage via CT; improves functional outcomes. - ST-elevation myocardial infarction (STEMI): used when primary PCI is not readily available within guideline time windows. - Massive/high-risk pulmonary embolism with hemodynamic instability. - Catheter or central line clearance for thrombotic occlusion.

Contraindications/cautions: active internal bleeding, recent surgery or trauma, history of intracranial hemorrhage, severe uncontrolled hypertension, bleeding diatheses, and recent ischemic stroke (within 3 months) for repeat use. Absolute contraindications also include suspected aortic dissection and active GI bleeding.

Adverse effects: primary concern is hemorrhage, particularly intracranial hemorrhage (most feared complication in stroke treatment), and reperfusion arrhythmias post-MI. Angioedema (orolingual) can occur, particularly in patients on ACE inhibitors.

Mechanism detail: Alteplase mimics endogenous tPA, binds fibrin, and activates plasminogen to plasmin within the clot, leading to fibrin degradation and clot lysis. This is distinct from anticoagulants (heparin, warfarin, DOACs) which prevent new clot formation but do not lyse existing clots, and from antiplatelets (aspirin, clopidogrel) which inhibit platelet aggregation.

Key boards association: Differentiate thrombolytics (tPA, streptokinase, tenecteplase, reteplase) from anticoagulants and antiplatelets in mechanism and clinical timing. Streptokinase is antigenic (risk of allergic reaction) and less fibrin-specific; alteplase and other recombinant tPAs are more fibrin-specific and non-antigenic.