A 28-year-old woman presents with episodic dark urine, especially in the morning, and jaundice. CBC: Hb 8.1 g/dL, reticulocyte count 8%, LDH 850 U/L, haptoglobin undetectable. Direct Coombs test is negative. Flow cytometry shows absence of CD55 and CD59 on erythrocytes (>50% affected). The first-line treatment for this patient to prevent thrombosis and hemolysis is:

• A Warfarin anticoagulation
• B Allogeneic stem cell transplantation immediately
• C Splenectomy
• D Eculizumab (anti-C5 complement inhibitor) ✓

Explanation

Paroxysmal nocturnal hemoglobinuria (PNH) is caused by a PIG-A gene mutation leading to deficiency of GPI-anchored complement regulatory proteins CD55 and CD59 on blood cells. Eculizumab (anti-C5 monoclonal antibody) blocks terminal complement activation, preventing MAC-mediated hemolysis and significantly reducing thrombotic events (the major cause of mortality in PNH). The TRIUMPH and SHEPHERD trials established eculizumab as the standard of care. Ravulizumab (longer-acting anti-C5) is an alternative. HSCT is reserved for PNH with bone marrow failure (aplastic anemia). Warfarin addresses thrombosis but not hemolysis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.