## G6PD Deficiency: Oxidative Hemolysis Mechanism **Key Point:** G6PD deficiency causes hemolysis through oxidative stress. The enzyme glucose-6-phosphatase dehydrogenase is critical for the pentose phosphate pathway, which generates NADPH—the cofactor needed to maintain reduced glutathione (GSH), the cell's primary antioxidant defense. ### Pathophysiology of Hemolysis 1. **Normal state:** G6PD catalyzes glucose-6-phosphate → 6-phosphogluconolactone, generating NADPH 2. **NADPH function:** Reduces oxidized glutathione (GSSG) back to reduced glutathione (GSH) 3. **GSH role:** Neutralizes reactive oxygen species (ROS) and hydrogen peroxide 4. **In G6PD deficiency:** Oxidative triggers (drugs, infections, fava beans) overwhelm the limited antioxidant capacity 5. **Result:** RBC membrane lipids and proteins oxidize → hemolysis ### Common Triggers (Mnemonic: **SANDS**) - **S**ulfonamides - **A**spirin (high-dose) - **N**itrofurantoin - **D**apsone - **S**ulfa drugs **Also:** Infections (bacterial, viral), fava beans, and other oxidative stressors ### Key Laboratory Features - **Heinz bodies:** Denatured hemoglobin precipitates (visible with supravital stain) - **Bite cells:** RBCs with Heinz bodies removed by splenic macrophages - **Hemoglobinuria:** During acute hemolytic episodes - **Reticulocytosis:** Elevated response to hemolysis **High-Yield:** G6PD deficiency is **episodic hemolysis** (triggered by oxidative stress), not chronic hemolysis. Between episodes, patients are asymptomatic. **Clinical Pearl:** Most common in males of African, Mediterranean, and Asian descent. X-linked inheritance means females are usually carriers but can be symptomatic if homozygous or have skewed X-inactivation.
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