A 35-year-old woman presents with fatigue, pallor, and episodic dark urine in the morning. CBC shows hemoglobin 7.2 g/dL, MCV 104 fL, reticulocyte count 8%. Peripheral smear shows polychromasia. LDH is elevated, haptoglobin is undetectable, and indirect bilirubin is elevated. Flow cytometry of peripheral blood shows absence of CD55 and CD59 on red blood cells. What is the MOST appropriate treatment for her underlying condition?
- A Prednisolone with splenectomy if refractory
- B Cyclophosphamide for clonal suppression
- C Iron supplementation to correct hemolytic anemia
- D Eculizumab (anti-C5 complement inhibitor) ✓
Explanation
The clinical triad of hemolytic anemia, hemoglobinuria (especially nocturnal/morning), and absence of GPI-anchored proteins (CD55/CD59) on flow cytometry is diagnostic of paroxysmal nocturnal hemoglobinuria (PNH). CD55 (decay-accelerating factor) and CD59 (protectin) normally protect red cells from complement-mediated lysis; their absence in PNH (due to somatic PIG-A mutation) renders cells susceptible to terminal complement activation. Eculizumab is a humanized monoclonal anti-C5 antibody that blocks terminal complement, dramatically reducing hemolysis, transfusion dependence, and thrombotic complications. Corticosteroids and splenectomy are used in autoimmune hemolytic anemia, not PNH. Iron supplementation may be needed (PNH patients lose iron in urine) but does not address the underlying hemolysis. Cyclophosphamide is not a treatment for PNH.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.