A 38-year-old woman from rural Maharashtra presents with progressive fatigue, dyspnea on exertion, and jaundice for 3 weeks. She has a history of recurrent episodes of fever and abdominal pain. On examination: pallor, icterus, splenomegaly (3 cm below costal margin), and dark urine. Hemoglobin 7.2 g/dL, reticulocyte count 12%, indirect bilirubin 4.8 mg/dL, haptoglobin <10 mg/dL. Peripheral blood smear shows spherocytes, polychromasia, and bite cells. Direct antiglobulin test (DAT) is negative. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: G6PD Deficiency with Acute Hemolytic Crisis ### Key Clinical Features **High-Yield:** The combination of acute hemolytic crisis (jaundice, dark urine, elevated indirect bilirubin, low haptoglobin) with a **negative DAT** and **bite cells** on peripheral smear is pathognomonic for G6PD deficiency. **Key Point:** Bite cells (or "blister cells") are RBCs with a characteristic appearance of a bite taken out of the cell, caused by Heinz body removal by the spleen. They are virtually diagnostic of G6PD deficiency during hemolysis. ### Peripheral Blood Smear Findings in G6PD Deficiency | Finding | Significance | |---------|-------------| | **Bite cells** | Pathognomonic; Heinz bodies removed by splenic macrophages | | **Polychromasia** | Reticulocytosis (RBC count 12% confirms this) | | **Schistocytes** | Absent (rules out MAHA) | | **Spherocytes** | May be present but not the dominant finding | | **DAT negative** | Rules out immune-mediated hemolysis | ### Why G6PD Deficiency Fits This Case 1. **Acute hemolytic crisis** triggered by infection (fever history suggests recent infection) 2. **Negative DAT** excludes autoimmune hemolytic anemia 3. **Bite cells** are the diagnostic hallmark 4. **High reticulocyte count** (12%) indicates bone marrow response 5. **Splenomegaly** from extramedullary hematopoiesis and RBC sequestration 6. **Geographic predisposition:** G6PD deficiency is common in Indian populations, particularly in malaria-endemic regions ### Pathophysiology **Clinical Pearl:** G6PD is an X-linked enzyme deficiency affecting the pentose phosphate pathway. During oxidative stress (infection, fava beans, certain drugs), RBCs cannot regenerate reduced glutathione, leading to oxidative damage, Heinz body formation, and hemolysis. ### Diagnostic Confirmation - **Heinz body stain** (supravital stain): Shows multiple Heinz bodies within RBCs - **G6PD enzyme assay:** Definitive test (but may be falsely normal immediately after hemolysis due to reticulocytosis) - **Osmotic fragility test:** Normal (rules out HS) [cite:Robbins 10e Ch 12] [cite:Harrison 21e Ch 135]