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

Question

Accepted Answer

D. Sickling of RBCs on deoxygenation or in hypotonic saline. ## 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.

Answer

A. Elevated reticulocyte count and indirect hyperbilirubinemia

Answer

B. Positive osmotic fragility test

Answer

C. Presence of target cells and polychromasia on blood smear

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

Comparison Table

Pathophysiology of Sickling

Why Other Options Are Non-Specific

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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