A 62-year-old woman with acute massive pulmonary embolism and haemodynamic instability (systolic BP 85 mmHg, heart rate 125/min, RV dysfunction on echo) is admitted to the ICU. She has no absolute contraindications to thrombolysis. What is the drug of choice for acute reperfusion therapy in this patient?

Explanation

## Thrombolysis in Massive PE with Haemodynamic Instability **Key Point:** Alteplase (tPA) is the drug of choice for acute thrombolysis in massive PE with haemodynamic instability and RV dysfunction. It is the only FDA-approved fibrinolytic agent for PE and offers the best chance of rapid clot dissolution and haemodynamic recovery. ### Indications for Thrombolysis in PE **Massive PE (Haemodynamically Unstable):** - Systolic BP < 90 mmHg for > 15 minutes OR - Requiring inotropes / vasopressors OR - Cardiac arrest - **Absolute indication for thrombolysis** [cite:Harrison 21e Ch 297] **Submassive PE (Haemodynamically Stable but with RV Dysfunction):** - Elevated troponin + RV dilation on echo - Consider thrombolysis if high-risk features present - Individualized decision based on bleeding risk ### Alteplase Dosing for PE | Parameter | Dose | | --- | --- | | **Bolus** | 10 mg IV over 1–2 minutes | | **Infusion** | 90 mg IV over 2 hours (remaining dose) | | **Total dose** | 100 mg | | **Monitoring** | Haemodynamics, oxygenation, bleeding signs | **High-Yield:** Alteplase achieves thrombolysis within 24–48 hours in ~80% of massive PE cases, with rapid improvement in RV function and haemodynamics. ### Mechanism of Alteplase 1. Binds fibrin in thrombus 2. Activates plasminogen → plasmin 3. Degrades fibrin scaffold 4. Dissolves clot rapidly (faster than anticoagulation alone) ### Comparison: Thrombolysis vs Anticoagulation Alone | Feature | Thrombolysis | Anticoagulation Alone | | --- | --- | --- | | **Onset of action** | Hours | Days | | **RV recovery** | Rapid (24–48 hrs) | Slow (weeks) | | **Mortality benefit** | Yes, in massive PE | No | | **Bleeding risk** | Higher (~10% major bleed) | Lower (~2–3%) | | **Indication** | Haemodynamic instability | Stable PE | **Clinical Pearl:** In this haemodynamically unstable patient with RV dysfunction, anticoagulation alone will be too slow to prevent cardiogenic shock and death. Thrombolysis is life-saving and should not be delayed. ### Contraindications to Thrombolysis - Active bleeding or bleeding disorder - Recent intracranial surgery / stroke (< 3 months) - Intracranial mass or metastases - Severe uncontrolled hypertension (SBP > 180 mmHg) - Recent major surgery (< 2 weeks) **Warning:** Do NOT withhold thrombolysis in massive PE due to minor bleeding risk — the mortality benefit outweighs the risk. Always check for absolute contraindications first.