A 28-year-old woman of Indian origin presents with jaundice, dark urine, and splenomegaly. Blood film shows spherocytes and polychromasia. Osmotic fragility test is positive. What is the most common cause of hereditary hemolytic anemia in this patient?

Explanation

## Most Common Hereditary Hemolytic Anemia **Key Point:** Hereditary spherocytosis (HS) is the most common hereditary hemolytic anemia in Caucasian and Indian populations, accounting for approximately 50% of all hereditary hemolytic anemias in these regions. ### Pathophysiology HS results from mutations in genes encoding red cell membrane proteins (spectrin, ankyrin, band 3, or protein 4.2). This leads to: 1. Loss of membrane surface area 2. Formation of spherical RBCs (spherocytes) 3. Osmotic fragility and splenic sequestration ### Diagnostic Features | Feature | Finding | |---------|----------| | **Blood film** | Spherocytes, polychromasia | | **Osmotic fragility** | Positive (RBCs lyse at higher saline concentrations) | | **Indirect bilirubin** | Elevated | | **Reticulocyte count** | Elevated (>2%) | | **LDH** | Elevated | | **Haptoglobin** | Decreased | ### Clinical Presentation - Jaundice (unconjugated hyperbilirubinemia) - Dark urine (due to hemoglobinuria) - Splenomegaly (from RBC sequestration) - Gallstones (from chronic hemolysis) - Aplastic crisis (from parvovirus B19 infection) **High-Yield:** The combination of **spherocytes + positive osmotic fragility test + family history** is pathognomonic for HS. **Clinical Pearl:** Splenectomy is curative in 70–80% of HS patients, as the spleen is the primary site of spherocyte destruction.