A 12-year-old boy with relapsed acute lymphoblastic leukemia receives rasburicase before chemotherapy to prevent tumor lysis syndrome. His pre-treatment screening shows G6PD deficiency. What is the main reason rasburicase must be avoided in this patient?
- A Rasburicase raises serum uric acid by blocking hepatic urate oxidase
- B Hydrogen peroxide generated during urate oxidation causes hemolysis and methemoglobinemia in G6PD-deficient red cells ✓
- C Rasburicase is renally cleared and precipitates acute kidney injury in enzyme-deficient patients
- D Rasburicase cross-reacts with the mutant G6PD protein and triggers complement-mediated hemolysis
Correct answer: B. Hydrogen peroxide generated during urate oxidation causes hemolysis and methemoglobinemia in G6PD-deficient red cells
Explanation
Rasburicase is recombinant urate oxidase that converts poorly soluble uric acid to allantoin, producing hydrogen peroxide as a byproduct. In G6PD-deficient erythrocytes, reduced glutathione cannot be regenerated adequately, so the peroxide oxidizes hemoglobin and membrane lipids, causing hemolysis and methemoglobinemia. This oxidative mechanism, not renal handling or immune cross-reactivity, is why G6PD deficiency is a contraindication to rasburicase.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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