A 40-year-old man presents with episodic haemoglobinuria (dark urine especially in the morning), anaemia (Hb 8.5 g/dL), thrombocytopenia, and a recent history of Budd-Chiari syndrome. Flow cytometry of peripheral blood shows a deficiency of CD55 and CD59 on red blood cells and granulocytes. The drug that has transformed outcomes in this condition by blocking complement C5 is:

• A Eculizumab (anti-C5 complement inhibitor) ✓
• B Rituximab (anti-CD20)
• C Defibrotide (for hepatic veno-occlusive disease)
• D Danazol (attenuated androgen for aplastic anaemia)

Explanation

Paroxysmal nocturnal haemoglobinuria (PNH) results from a somatic PIGA gene mutation causing deficiency of GPI-anchored complement regulatory proteins CD55 (DAF) and CD59 (protectin), leading to uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody against complement C5, blocks the terminal complement cascade, dramatically reducing haemolysis, transfusion dependence, and thrombotic risk (including Budd-Chiari syndrome and cerebral vein thrombosis). Ravulizumab (long-acting anti-C5) is a newer approved alternative.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.