Hereditary Spherocytosis (HS)

Epidemiology and Etiology:

• Intrinsic defect in the red cell membrane skeleton
• Red cells are spheroid, less deformable, and vulnerable to splenic sequestration and destruction
• Northern Europe highest prevalence
• Autosomal dominant
• 75%
• 25% with compound heterozygosity and more severe phenotype

Common sites:

Gross features:

• Jaundice (mild)
• Cholelithiasis (pigment stones (40-50%)
• Splenomegaly characteristically (moderate) (500-1000 g)

Microscopic features:

• Peripheral blood smear:
• Spherocytosis
• Small
• Hyperchromatic
• Lacking central pallor
• Reticulocytosis
• Bone marrow:
• Erythroid hyperplasia
• Hemosiderosis

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

• Diverse loss of function mutations that lead to an insufficiency of membrane skeletal components
• Ankyrin mutation
• Band 3 mutation
• Spectrin mutation
• Band 4.2 mutation
• Mutations result in red cell membrane/cytoskeleton instability
• Loss of pieces of membrane, forcing the RBC to assume a sphere shape over time
• Decrease in life span of RBC to 10-20 d, down from 120 d normally

Other features:

• Anemia
• Jaundice
• splenomegaly
• Splenectomy is beneficial
• Aplastic crisis may be triggered by acute parvovirus infection
• Sudden worsening of anemia due to reduced life span of HS red cells

References:

• Kumar V, Abbas AK, Fausto N, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease, 8^th ed. (2010)