A 2-year-old girl from Delhi presents with hemolytic anemia, jaundice, and dark urine after eating fava beans. Laboratory tests show: - Hemoglobin: 8.5 g/dL (baseline 11 g/dL) - Reticulocyte count: 8% (elevated) - Serum bilirubin: 4.2 mg/dL (conjugated 0.3 mg/dL) - Peripheral blood smear: Heinz bodies, schistocytes - RBC glucose-6-phosphatase dehydrogenase (G6PD) activity: 5% of normal The child is hemodynamically stable. What is the most appropriate immediate next step?

Explanation

## G6PD Deficiency and Acute Hemolytic Crisis This patient has **G6PD deficiency**, a glycolytic enzyme defect affecting the pentose phosphate pathway. G6PD catalyzes the first step of the pentose phosphate pathway, producing NADPH, which is essential for maintaining reduced glutathione (GSH) and protecting RBCs from oxidative stress. ### Pathophysiology of G6PD Deficiency **Key Point:** G6PD deficiency → ↓ NADPH → ↓ reduced glutathione (GSH) → impaired antioxidant defense → oxidative hemolysis when exposed to oxidative triggers (fava beans, sulfonamides, aspirin, infections). **Mnemonic for G6PD triggers:** **AAABBBCCCC** - **A**spirin, **A**ntibiotics (sulfonamides, nitrofurantoin), **A**cetaminophen - **B**road beans (fava), **B**arbiturates, **B**lue dyes - **C**ontaminated food, **C**old exposure, **C**hemical oxidants ### Acute Management of Hemolytic Crisis **High-Yield:** In an acute G6PD hemolytic crisis, the FIRST step is to **identify and remove the offending agent**. The hemolysis is self-limited because older RBCs (which have lower G6PD activity) are preferentially destroyed, while younger RBCs (with higher enzyme activity) survive. **Clinical Pearl:** Most acute hemolytic episodes in G6PD deficiency resolve spontaneously within 7–14 days once the trigger is removed, even without transfusion. The reticulocytosis (8%) indicates the bone marrow is compensating appropriately. ### Management Algorithm ```mermaid flowchart TD A[G6PD hemolytic crisis]:::outcome --> B{Hemodynamically stable?}:::decision B -->|Yes| C[Remove offending agent]:::action C --> D[Monitor Hb and reticulocytes]:::action D --> E[Supportive care: hydration, folic acid]:::action E --> F[Most crises resolve in 7-14 days]:::outcome B -->|No| G[Transfusion if Hb < 7 g/dL or symptomatic]:::action G --> H[Exchange transfusion only if severe/life-threatening]:::urgent ``` ### Why NOT the Other Options | Option | Why Incorrect | | --- | --- | | Exchange transfusion + IVIG | Not indicated in a stable patient with mild-to-moderate hemolysis. Exchange transfusion is reserved for severe hemolysis (Hb < 7 g/dL with symptoms) or life-threatening crisis. IVIG is used for immune-mediated hemolysis, not oxidative hemolysis. | | Corticosteroids | Ineffective in G6PD-mediated oxidative hemolysis. Steroids are indicated for immune hemolytic anemia (warm/cold agglutinin disease), not enzyme deficiency. | | Splenectomy | Not indicated. Splenectomy is used for hereditary spherocytosis and immune hemolytic anemia, not G6PD deficiency. It does not prevent oxidative hemolysis and carries surgical risk. | ### Supportive Care Details 1. **Discontinue fava beans and other triggers** 2. **Maintain hydration** — prevents acute kidney injury from hemoglobinuria 3. **Folic acid supplementation** (1 mg daily) — supports increased RBC production during reticulocytosis 4. **Monitor hemoglobin and reticulocyte count** — assess recovery trajectory 5. **Transfusion only if** Hb < 7 g/dL with symptoms (dyspnea, tachycardia, altered mental status) ### Long-Term Management - Educate family on triggers (fava beans, sulfonamides, aspirin, NSAIDs) - Genetic counseling (X-linked recessive inheritance) - Periodic monitoring of hemoglobin - Avoid unnecessary medications