A 42-year-old woman presents with fatigue, haemoglobinuria in the morning, pancytopaenia, and a positive flow cytometry showing GPI-anchor deficient RBCs (PNH clone 38%). Which complication is the leading cause of death in paroxysmal nocturnal haemoglobinuria (PNH)?
- A Aplastic anaemia and bone marrow failure
- B Infection from complement deficiency
- C Thrombosis (venous and arterial, especially hepatic vein — Budd-Chiari syndrome) ✓
- D Acute leukaemic transformation
Explanation
Thrombosis is the leading cause of death in PNH, occurring in ~40% of patients and accounting for >50% of PNH-related mortality. Thrombi can occur at unusual sites including the hepatic vein (Budd-Chiari syndrome), portal vein, mesenteric vein, cerebral venous sinuses, and renal veins. The pathogenesis involves complement-mediated platelet activation on GPI-deficient platelets and impaired fibrinolysis from nitric oxide scavenging by free haemoglobin. Eculizumab (anti-C5 complement inhibitor) and ravulizumab dramatically reduce haemolysis and thrombosis risk, making anticoagulation considerations important alongside complement inhibition.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.