Which feature best distinguishes sickle cell disease from hereditary spherocytosis in a patient with chronic hemolytic anemia and jaundice?

Explanation

## Sickle Cell Disease vs. Hereditary Spherocytosis ### Morphologic and Functional Distinctions **Key Point:** Sickling of RBCs on deoxygenation (or in hypotonic saline with reducing agents) is pathognomonic for sickle cell disease and is absent in hereditary spherocytosis. This morphologic change reflects the polymerization of deoxygenated HbS and is the definitive discriminator. ### Comparison Table | Feature | Sickle Cell Disease | Hereditary Spherocytosis | | --- | --- | --- | | **RBC morphology** | **Sickle cells, target cells** | **Spherocytes** | | **Sickling on deoxygenation** | **Yes (pathognomonic)** | No | | **Osmotic fragility test** | Normal or decreased | **Increased (fragile)** | | **Hemoglobin** | HbS (abnormal β-globin) | Normal (membrane defect) | | **Spleen function** | Autoinfarction (nonfunctional) | Functional (may enlarge) | | **Vaso-occlusive crises** | Yes | No | | **Gallstones** | Common (pigment) | Common (pigment) | | **Diagnosis** | Hemoglobin electrophoresis, sickle prep | Osmotic fragility, eosin-5-maleimide (EMA) binding, genetic testing | ### Pathophysiology of Sickling **High-Yield:** When deoxygenated, HbS polymerizes into long fibers that distort the RBC into the characteristic sickle shape. This polymerization is specific to HbS and does NOT occur in hereditary spherocytosis, where the defect is in the red cell membrane (spectrin, ankyrin, band 3) and the cells are spherical, not sickled. **Mnemonic:** **SICKLE** = **S**tructural hemoglobin defect (HbS polymerization); **H**ereditary **S**phero = **S**tructure membrane defect (no sickling). ### Why Other Options Are Non-Specific - **Osmotic fragility:** Increased in hereditary spherocytosis (spherocytes are fragile); normal or decreased in sickle cell disease. This is a discriminator, but in the opposite direction. - **Target cells, polychromasia, reticulocytosis, hyperbilirubinemia:** All are seen in BOTH conditions due to chronic hemolysis. Not specific. **Clinical Pearl:** The sickle prep (deoxygenation with sodium metabisulfite) is a rapid bedside test for HbS. A positive sickle prep rules in sickle cell disease or trait and rules out hereditary spherocytosis.