A 30-year-old African American man develops acute intravascular hemolysis with hemoglobinuria after taking primaquine for malaria prophylaxis. Peripheral smear shows bite cells and Heinz bodies. His G6PD enzyme activity is markedly reduced. G6PD A– is the most common variant in sub-Saharan Africa. Why are older red cells preferentially destroyed while reticulocytes and young RBCs survive during an oxidative challenge?

• A Older RBCs have accumulated more mutant hemoglobin and are preferentially targeted by splenic macrophages via opsonization
• B Band 3 protein on older RBCs is phosphorylated, making them more susceptible to complement-mediated lysis
• C Reticulocytes and young RBCs contain residual G6PD protein from erythropoiesis; aging RBCs lose G6PD activity because the mutant enzyme is thermolabile and degrades faster than normal, leaving old cells unprotected against oxidative denaturation of hemoglobin ✓
• D Older RBCs have exhausted their 2,3-DPG stores, shifting the hemoglobin-oxygen dissociation curve and increasing susceptibility to oxidative damage

Explanation

In G6PD A– (the African type), the enzyme is synthesized normally but is structurally unstable and degrades with RBC aging (half-life ~13 days vs. ~60 days for normal G6PD). Young RBCs and reticulocytes retain sufficient G6PD to maintain NADPH production via the hexose monophosphate shunt, protecting against oxidative stress. Older RBCs have negligible G6PD activity, cannot regenerate glutathione, and are destroyed when exposed to oxidants (e.g., primaquine, dapsone, infections). This explains the self-limiting nature of hemolysis in G6PD A– (reticulocytosis rescues the patient).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.