A 62-year-old woman with acute pulmonary embolism and hemodynamic instability (systolic BP 85 mmHg, RV dysfunction on echo) is admitted to the ICU. After starting unfractionated heparin, what is the drug of choice for immediate thrombolysis?

Explanation

## Thrombolysis in Massive PE **Key Point:** Alteplase (recombinant tissue plasminogen activator, rt-PA) is the FDA-approved and guideline-recommended thrombolytic agent for hemodynamically unstable (massive) pulmonary embolism. ### Indications for Thrombolysis in PE **High-Yield:** Thrombolysis is reserved for **massive PE** (hemodynamic instability: systolic BP <90 mmHg for >15 minutes, signs of shock, RV dysfunction on imaging) or **submassive PE** with RV dysfunction and elevated biomarkers (troponin, BNP) in selected cases. ### Why Alteplase is Preferred | Agent | Fibrin Selectivity | Approval for PE | Onset | Bleeding Risk | Cost | |-------|-------------------|-----------------|-------|---------------|------| | **Alteplase** | High | FDA-approved | Rapid (10–30 min) | Moderate | Standard | | Urokinase | Low | Not approved (discontinued) | Rapid | High | High | | Streptokinase | Low | Not approved for PE | Slow | High | Low | | Tenecteplase | High | Not approved for PE | Rapid | Moderate | High | **Clinical Pearl:** Alteplase has the highest fibrin selectivity among thrombolytics, meaning it preferentially activates plasminogen bound to fibrin clots rather than circulating plasminogen. This reduces systemic fibrinolysis and bleeding complications compared to non-selective agents like streptokinase and urokinase. ### Dosing of Alteplase for PE - **Bolus:** 10 mg IV over 1–2 minutes - **Infusion:** 90 mg IV over 2 hours (15 mg/hr for first hour, then 17.5 mg/hr for next hour) - **Total dose:** 100 mg **Mnemonic:** **MASSIVE PE = ALTEPLASE** (Massive PE = Anticoagulation + Lysis with Alteplase for Systemic Embolism) ### Contraindications to Thrombolysis - Active bleeding or bleeding disorder - Recent surgery, trauma, or intracranial pathology - Uncontrolled hypertension (SBP >180 mmHg) - Ischemic stroke within 3 months - Severe hepatic or renal disease **Warning:** Do NOT use streptokinase in PE — it is not approved, has high bleeding risk, and is antigenic (contraindicated if prior streptococcal infection or prior streptokinase use within 6 months). **Tip:** Alteplase should be given AFTER heparin is started. Continue UFH during and after thrombolysis. Monitor for reperfusion (improved oxygenation, hemodynamics) and bleeding complications (oozing from lines, hematuria, GI bleeding). [cite:Harrison 21e Ch 297]