reteplase

**Class/Mechanism:** Thrombolytic (fibrinolytic) agent, a recombinant tPA variant (r-PA). It is produced in E. coli and is non-glycosylated, with the finger, EGF, and kringle-1 domains deleted. This gives it a longer half-life (~15-20 min) than alteplase (~5 min), so it can be given as bolus doses rather than an infusion. It binds fibrin less avidly than alteplase (reduced fibrin specificity). Like other tPAs, it cleaves plasminogen to plasmin, and plasmin degrades fibrin (clot lysis) and increases fibrin degradation products and D-dimer. Serum fibrinogen may fall, and PT/aPTT may rise.

**Dosing (STEMI):** 10 units IV bolus over 2 minutes, then a second 10-unit bolus 30 minutes later (double-bolus). It is given with aspirin and heparin as adjunctive therapy.

**Indications:** Acute STEMI, to improve ventricular function and reduce mortality and heart failure. It is used when PCI cannot be done within ~120 minutes of first medical contact, and ideally within 12 hours of symptom onset (benefit is greatest within the first few hours). It is not approved for acute ischemic stroke (alteplase and tenecteplase are used there) or for PE, though these uses appear in comparisons of thrombolytics.

**Comparison with other fibrinolytics:** - Alteplase (tPA): fibrin-specific; used in STEMI, ischemic stroke (within 3-4.5 h), and massive PE. - Tenecteplase (TNK-tPA): single bolus; more fibrin-specific and resistant to PAI-1. - Reteplase (r-PA): double bolus; less fibrin-specific. - Streptokinase: non-fibrin-specific; can cause allergic reactions and hypotension; antibodies develop after prior streptococcal infection or prior use. - Urokinase: directly activates plasminogen.

**Adverse effects:** Bleeding is the major one: GI, GU, intracranial hemorrhage (the most feared), and bleeding at puncture sites. Others include reperfusion arrhythmias (e.g., accelerated idioventricular rhythm), hypotension, and rarely allergic reactions. Treat serious bleeding by stopping the drug and giving cryoprecipitate or fresh frozen plasma (to replace fibrinogen), and aminocaproic acid or tranexamic acid (antifibrinolytics that inhibit plasmin/plasminogen activation).

**Contraindications (high yield):** - Absolute: prior intracranial hemorrhage, ischemic stroke within 3 months, known intracranial neoplasm or AVM, active internal bleeding, suspected aortic dissection, significant head or facial trauma within 3 months, intracranial or spinal surgery within 2 months, and severe uncontrolled hypertension (>180/110 mmHg). - Relative: anticoagulant use with elevated INR, recent major surgery or trauma, pregnancy, prolonged CPR, and history of chronic severe hypertension.

**Boards pearls:** Thrombolytics are best for STEMI when PCI is unavailable. They do not help in NSTEMI/unstable angina and may be harmful. Aminocaproic acid reverses thrombolytic-induced bleeding. Reteplase is a tPA analog, so think of the "-teplase" suffix as a tPA derivative (alteplase, reteplase, tenecteplase).