Hereditary spherocytosis
- Lesion
An inherited weakness of the red cell skeleton makes cells lose membrane and become spheres that the spleen destroys. Removing the spleen fixes the anaemia.
What it is
Hereditary spherocytosis (HS) is the commonest inherited membrane disorder in people of northern European ancestry and usually autosomal dominant. Mutations in ankyrin, band 3, spectrin or protein 4.2 weaken the vertical links between the membrane skeleton and the lipid bilayer. The cells shed membrane as they age and become small spheres that cannot deform through the splenic cords, where they are trapped and eaten. The result is chronic extravascular haemolysis with splenomegaly, jaundice and gallstones.
Structure
- Smear: spherocytes, polychromasia from reticulocytes; Howell–Jolly bodies after splenectomy.
- Spleen: enlarged, congested cords packed with red cells, many macrophages with red cell debris and haemosiderin.
- Marrow: erythroid hyperplasia.
Step by step
- A mutation reduces a protein linking spectrin to band 3 (ankyrin, protein 4.2) or spectrin itself.
- The bilayer is poorly anchored and sheds small vesicles as the cell ages.
- Surface area falls relative to volume: the disc becomes a sphere.
- Spheres cannot squeeze from cords into sinusoids; trapped, they lose more membrane in the acidic, glucose-poor splenic environment.
- Macrophages remove them: extravascular haemolysis.
Markers
- Spherocytes
- High MCHC
- Negative direct Coombs
- Reduced EMA binding
Clinical notes
- Variable severity: from neonatal jaundice needing exchange transfusion to mild anaemia found in adulthood.
- Splenectomy raises the risk of sepsis by encapsulated bacteria; an overlooked accessory spleen can cause relapse.
In the lab
- Eosin-5′-maleimide binding by flow cytometry is reduced (it labels band 3).
- Increased osmotic fragility; reticulocytosis; high MCHC.
Test yourself
Think of the answer, then tap the question to see it.
Which proteins are most commonly mutated in hereditary spherocytosis?
Ankyrin, band 3, spectrin and protein 4.2.
Which test result separates HS from warm autoimmune haemolytic anaemia?
A negative direct Coombs test in HS.
What happens to the anaemia and the spherocytes after splenectomy?
The anaemia corrects, but the spherocytes persist in the blood.
Elsewhere in DurgiPedia
Connections
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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Hereditary spherocytosis: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.