Hereditary spherocytosis

Hereditary spherocytosis

Updated: 07/14/2024

© Jun Wang, MD, PhD

 

General features

• Most common cause of hemolytic anemia due to a red cell membrane defect
• Caused by mutations in genes for membrane/cytoskeletal proteins
• Autosomal dominant for mutations in ANK1, SPTB or SLC4A1
• Autosomal recessive for SPTA1 and EPB42
• Hemolysis due to impaired RBC elasticity

Pathogenesis

• Variants in one of the five genes (ANK1, SPTA1, SPTB, SLC4A1, and EBP42) that encode the erythrocyte membrane proteins ankyrin, alpha-spectrin, beta-spectrin, band 3, and band 4.2, respectively
• Mutations of these proteins cause reduced membrane stability

 

Clinical features

• Clinical features: splenomegaly, anemia, jaundice
• Splenectomy in severe cases usually curative

Laboratory findings

• Peripheral blood

o   Spherocytes: small, hyperchromic RBC lacking the central zone of pallor area

o   Normal MCH, high MCHC

o   Normal to decreased MCV

o   Normal to increased RDW

o   Increased reticulocytes

• Chemistries:

o   Increased LDH and indirect bilirubin

o   Decreased haptoglobin

• Bone marrow: Erythroid hyperplasia
• Elevated reticulocyte count

Diagnosis

• Family history
• Increased osmotic fragility
• Confirmation tests: EMA binding, osmotic fragility, or osmotic gradient ektacytometry (OGE)
• Genetic testing
• DAT (direct antiglobulin test) to exclude autoimmune causes of spherocytosis and hemolysis

Management

• Preventing or minimizing complications of chronic hemolysis and anemia
• Treatment of hyperbilirubinemia
• Folate supplementation
• Erythropoietin
• Transfusion
• Splenectomy

 

 

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