Hereditary Spherocytosis

Introduction

• Hereditary Spherocytosis (HS) is the most common hemolytic anemia due to a red blood cell (RBC) membrane disorder.
• HS is due to a mutation in spectrin, ankyrin, band 3 protein, or protein 4.2. These proteins normally maintain the biconcave disc shape of RBCs.
• With a defect in these proteins, the RBC typically takes on a spherical shape.
• These RBCs are not as flexible as the regular RBC, and can undergo hemolysis when trying to pass through the small capillaries of the reticuloendothelial system (RES).
• This then causes the spleen to become engorged, which can be palpable on physical exam.

Image: Peripheral blood smear from a patient with HS. Numerous sphere-shaped RBCs are seen. https://en.wikipedia.org/wiki/Hereditary_spherocytosis#/media/File:Hereditary_Spherocytosis_smear_2010-03-17.JPG

• HS is thought to be under diagnosed as a cause for neonatal hyperbilirubinemia.
• A mean corpuscular hemoglobin concentration (MCHC) of >36.0 g/dL can alert providers that HS could be a possibility
• The treatment for HS can be blood transfusions, which can cause secondary hemochromatosis from iron overload.
• A splenectomy is another treatment option in moderate to severe cases.
• Following a splenectomy, patients will need to be immunized against encapsulated organisms such as:
  • Streptococcus pneumoniae
  • Haemophilus influenzae
  • Neisseria meningitidis

Epidemiology:

• Inheritance pattern is 75% autosomal dominant
• Incindence of HS is 1/5000 in individuals of European descent

Clinical Presentation and Lab Findings

Anemia, jaundice, and splenomegaly are common clinical features of disease. The degree of of anemia varies based on the severity of symptoms

• Mild: 20-30% of cases
  • May have no anemia, modest reticulocytosis, a minimal juandice or splenomegaly
  • Detected in adolescence or adulthood
• Moderate: 60 to 75% of cases
  • Patients are moderately anemic, with high reticulocyte counts and elevated bilirubin
  • Detected in infancy or childhood
  • May require occasional RBC transfusions
• Severe: 5% of cases
  • Characterized by marked hemolysis, anemia, splenomegaly, and hyperbilrubinemia
  • Pattern of inheritance is usually recessive
  • Requires regular need for RBC transfusions

Lab Findings:

• Increased MCHC
• Spherocytes on peripheral smear
• Howell Jolly bodies on peripheral smear following splenectomy
• Negative Coombs test
• Increased osmotic fragility on acidified glycerol lysis test
• Abnormal eosin-5-maleimide binding test

Treatment and Complications

Treatment

• There is no specific treatment for HS apart from supportice care, which consists of the following modalities:
• Folic acid supplementation
  • Need for folic acid increases with marked increase in hematopoiesis
• Blood transfusion
  • Transfusion dependence is present in approximately 70-80% of HS affected infants, secondary to inadequate bone marrow compensation
  • Need for continuous tranfusions decreases to 30% after first year of life
• Splenectomy
  • Decision to proceed with splenectomy must take into account
    • Severity of hemolysis
    • Age of patient
    • Associated risk factors (e.g. sepsis)

Complications

• Pigment gallstones
• Aplastic crisis from parvovirus B19 infection

References

1. Bolton‐Maggs, Paula HB, et al. "Guidelines for the diagnosis and management of hereditary spherocytosis–2011 update." British journal of haematology 156.1 (2012): 37-49.
2. Christensen, Henry. “Hereditary Spherocytosis in Neonates with Hyperbilirubinemia”. PEDIATRICS Vol. 125 No. 1 January 1, 2010 pp. 120 -125
3. Shah, Vega. “Hereditary Spherocyosis” PEDIATRICS IN REVIEW Vol. 25 No. 5 May 1, 2004 pp. 168 -172