Hereditary Spherocytosis

Hereditary spherocytosis (HS) is an autosomal dominant condition characterised by mutations in red cell membrane proteins. The majority of mutations are in ankyrin and ß-spectrin genes, with a minority occuring in the red cell membrane protein, band 3 and α-spectrin genes. This results in a destabilised membrane and spherocytosis.

Clinical features:

• Phenotypic severity ranges from asymptomatic to severe chronic haemolysis.
• Most patients have compensated haemolysis with normal haemoglobin concentration but a reticulocytosis.
• Patients may also have an increased frequency of choledocholithiasis.
• Pregnancy may cause severe anaemia in non-splenectomised patients.

Diagnosis:

• In patients with a strong family history, typical blood film findings with a negative DCT are enough to confirm the diagnosis.
• Otherwise, the eosin-5-maleimide (EMA) binding test is the screening test of choice.
  • EMA binds to transmembrane proteins.
  • Fluorescence is measured via flow cytometry. 
  • HS results in a decrease in EMA binding and reduced fluorescence. 

Blood film features:

• Anaemia is usually mild or absent
• Spherocytosis
• Polychromasia and polychromatic reticulocytes

Other features to look out for:

• Features of splenectomy:
  • Howell-Jolly bodies
  • Pappenheimer bodies
  • Acanthocytes
  • Target cells
  • Spherocytes
  • Stomatocytes
  • Thrombocytosis
  • Platelet anisocytosis
  • Lymphocytosis

Treatment:

• Supportive measures:
  • Folic acid supplementation.
  • Transfusion support during haemolytic crises.
• Splenectomy is the treatment of choice for patients with severe HS.
  • Splenectomy should ideally be delayed till after the age of 6.
  • Patients should be vaccinated against encapsulated bacteria before splenectomy.
  • Thromboprophylaxis should be given to all patients undergoing splenectomy.

Other resources:

• BCSH Guideline: Hereditary Spherocytosis (2011)
• ASH Image Bank: HS