A 48-year-old woman with acute massive pulmonary embolism and cardiogenic shock (systolic BP 85 mmHg, RV dysfunction on echocardiography) is admitted to the ICU. What is the drug of choice for immediate reperfusion therapy?

Explanation

## Thrombolysis in Massive (Haemodynamically Unstable) PE **Key Point:** Alteplase (tPA) is the drug of choice for acute thrombolysis in haemodynamically unstable (massive) pulmonary embolism with cardiogenic shock and/or RV dysfunction. ### Indications for Thrombolysis in PE **High-Yield:** Thrombolysis is indicated in: 1. **Massive PE** — haemodynamic instability (SBP <90 mmHg or drop ≥40 mmHg) with RV dysfunction 2. **Submassive PE** — RV dysfunction + myocardial injury (elevated troponin/BNP) + high-risk features (consider case-by-case) ### Thrombolytic Agents in PE | Agent | Dose | Infusion Time | Fibrin-Specificity | Notes | |-------|------|----------------|-------------------|-------| | **Alteplase (tPA)** | 100 mg | 2 hours | High | **Preferred agent** for PE thrombolysis | | Streptokinase | 250,000 IU bolus, then 100,000 IU/hr | 24 hours | Low | Older agent; less commonly used | | Tenecteplase | Weight-based (30–50 mg) | Single bolus | High | Faster infusion; emerging alternative | **Clinical Pearl:** Alteplase 100 mg IV over 2 hours (or 10 mg bolus, then 90 mg over 2 hours) is the standard regimen. Anticoagulation with UFH is continued (or initiated) concurrently [cite:Harrison 21e Ch 298]. ### Mechanism of Benefit ```mermaid flowchart TD A[Massive PE with shock]:::urgent --> B[Alteplase thrombolysis]:::action B --> C[Rapid thrombus dissolution]:::outcome C --> D[Reduced RV afterload]:::outcome D --> E[Restored haemodynamics]:::outcome E --> F[Improved survival]:::outcome G[Anticoagulation UFH]:::action --> B G --> H[Prevents new thrombus]:::outcome ``` **Warning:** Thrombolysis carries a significant bleeding risk (major bleeding ~10–20%, intracranial haemorrhage ~1–2%). Absolute contraindications include active bleeding, recent stroke, and intracranial pathology. ### Comparison: Thrombolysis vs. Anticoagulation Alone | Feature | Thrombolysis | Anticoagulation Only | |---------|--------------|---------------------| | **Indications** | Massive PE (shock) | Stable/submassive PE | | **Mortality benefit** | Yes (in massive PE) | No | | **Bleeding risk** | High (~10–20%) | Lower (~2–5%) | | **Time to effect** | Hours | Days | **Mnemonic:** **MASSIVE PE = THROMBOLYSIS** — Massive (haemodynamic instability) → Alteplase (thrombolysis) → Survival improved.