Hereditary Spherocytosis

Key Features

Essentials of Diagnosis

• Anemia and jaundice

• Splenomegaly

• Positive family history of anemia, jaundice, or gallstones

• Spherocytosis with increased reticulocytes

• Increased osmotic fragility

• Negative direct antiglobulin test (DAT)

General Considerations

• Relatively common inherited hemolytic anemia

• Occurs in all ethnic groups, but is most common in persons of northern European ancestry, in whom the incidence is about 1:5000

• Disease is inherited in an autosomal dominant fashion in about 75% of cases; the remaining cases are thought to be autosomal recessive or due to de novo mutations

Clinical Findings

Symptoms and Signs

• Hemolysis causes significant neonatal hyperbilirubinemia in 50% of affected children

• Splenomegaly subsequently develops in the majority and is often present by age 5 years

• Jaundice is variably present and in many patients may be noted only during infection

• Patients with significant chronic anemia may complain of pallor, fatigue, or malaise

• Intermittent exacerbations of the anemia

  • Caused by increased hemolysis, splenic sequestration or by aplastic crises

  • May be associated with severe weakness, fatigue, fever, abdominal pain, or even heart failure

Diagnosis

• Most patients have mild chronic hemolysis with hemoglobin levels of 9–12 g/dL

• In some cases, hemolysis is fully compensated and the hemoglobin level is in the normal range

• Anemia is usually normocytic and hyperchromic, and many patients have an elevated mean corpuscular hemoglobin concentration

• Peripheral blood smear shows numerous microspherocytes and polychromasia

• WBC and platelet counts are usually normal

• Serum bilirubin usually shows an elevation in the unconjugated fraction

Treatment

• Supportive measures include the administration of folic acid to prevent the development of red cell hypoplasia due to folate deficiency

• Acute exacerbations of anemia, due to increased rates of hemolysis or to aplastic crises caused by infection with human parvovirus, may be severe enough to require red cell transfusions

• Splenectomy

  • May be indicated depending on clinical severity and always results in significant improvement

  • Should be postponed until the child is at least age 5 years because of the greater risk of postsplenectomy sepsis prior to this age, except in unusually severe cases

  • All patients scheduled for splenectomy should be immunized with pneumococcal, Haemophilus influenzae type b (Hib), and meningococcal vaccines prior to the procedure, and some clinicians recommend penicillin prophylaxis afterward

  • Asplenic patients with fever should be promptly evaluated for severe infection

  • Splenectomy prevents the subsequent development of cholelithiasis and eliminates the need for the activity restrictions

Outcome

Complications

• Severe jaundice may occur in the neonatal period and, if not controlled by phototherapy, may occasionally require exchange transfusion

• Intermittent or persistent splenomegaly occurs in 10–25% of patients and may require removal

• Splenectomy is associated with an increased risk of overwhelming bacterial infections, particularly with pneumococci