tenecteplase

Tenecteplase is a genetically engineered variant of alteplase (tPA) with three amino acid substitutions that confer increased fibrin specificity, resistance to plasminogen activator inhibitor-1 (PAI-1), and a longer plasma half-life (~20 minutes vs. ~5 minutes for alteplase). Mechanism: binds fibrin in a thrombus and converts plasminogen to plasmin, which degrades fibrin and dissolves the clot. Clinical uses: (1) STEMI - given as a single weight-based IV bolus, particularly useful in pre-hospital or transfer settings where PCI is not immediately available (pharmacoinvasive strategy); (2) increasingly used off-label/investigationally for acute ischemic stroke as an alternative to alteplase due to easier administration (single bolus vs. infusion) and comparable or superior efficacy in some trials (e.g., EXTEND-IA TNK). Contraindications/adverse effects: major risk is hemorrhage, especially intracranial hemorrhage; contraindicated in patients with active internal bleeding, history of hemorrhagic stroke, recent major surgery/trauma, severe uncontrolled hypertension, or bleeding diatheses. Monitoring involves clinical assessment for bleeding, neurological changes, and reperfusion arrhythmias. Key teaching points for boards: differentiate tenecteplase from alteplase (reteplase, another variant, also bolus-dosed but less fibrin-specific); understand the fibrinolytic cascade and the role of plasmin; recognize the importance of timing (door-to-needle time) in STEMI and stroke management; know contraindications to thrombolysis.