A 40-year-old man has episodes of dark-colored urine in the morning and is found to have hemolytic anemia with thrombocytopenia. Flow cytometry shows absence of CD55 and CD59 on RBCs. Which mechanism leads to hemolysis in this condition?

• A Warm IgG antibodies causing extravascular hemolysis in spleen
• B Complement-mediated intravascular hemolysis due to GPI-anchor deficiency ✓
• C Microangiopathic hemolysis from fibrin strand shearing of RBCs
• D Osmotic fragility from spectrin/ankyrin mutations

Explanation

This is paroxysmal nocturnal hemoglobinuria (PNH), caused by a somatic PIGA mutation leading to deficiency of GPI-anchored complement regulatory proteins CD55 (DAF) and CD59 (protectin). Without these, complement activation on the RBC surface proceeds unchecked to the membrane attack complex, causing intravascular hemolysis. The characteristic morning hemoglobinuria reflects overnight respiratory acidosis activating complement.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.