Hereditary spherocytosis
Hereditary spherocytosis is an inherited red cell membrane defect, usually autosomal dominant, that produces rigid spherocytes trapped and destroyed in the spleen. It presents with anemia, jaundice, splenomegaly, and pigment gallstones, is diagnosed by spherocytes with elevated MCHC and a negative direct antiglobulin test, and is confirmed by eosin-5-maleimide binding or osmotic fragility testing, with folic acid and splenectomy as the mainstays of treatment.
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What this article covers
- Overview
Definition: hereditary spherocytosis (HS) is an inherited defect of the red cell membrane cytoskeleton that causes erythrocytes to lose surface area relative to volume, adopt a spherical rather than…
- Epidemiology
Most common inherited hemolytic anemia in people of Northern European descent, where it is the leading cause of an inherited hemolytic anemia requiring clinical attention.
- Risk factors
Family history of hemolytic anemia, jaundice, splenectomy, or gallstones at a young age: the strongest clue, reflecting the usual autosomal dominant transmission.
- Pathophysiology
Primary defect: mutations in ankyrin, alpha- or beta-spectrin, band 3, or protein 4.2 disrupt the vertical linkages anchoring the spectrin-actin cytoskeleton to the overlying lipid bilayer.
- Clinical features
Anemia: ranges from asymptomatic/fully compensated hemolysis with a normal hemoglobin to symptomatic anemia (fatigue, pallor) with more brisk, poorly compensated hemolysis in severe disease.
- Differential diagnosis
Warm autoimmune hemolytic anemia: also produces spherocytes and extravascular splenic hemolysis, but is acquired, typically has no family history, and is distinguished by a positive direct…
- Diagnosis
Establish the diagnosis with the classic laboratory triad, then confirm: spherocytes on peripheral smear together with an elevated MCHC (often above 36 g/dL) and elevated RDW, plus a negative direct…
- Management
All patients receive folic acid supplementation: folic acid 1 to 2 mg orally once daily, continued indefinitely, to support the increased erythropoietic demand of chronic hemolysis and prevent…
- Complications
Aplastic crisis from parvovirus B19: the most dramatic acute complication, causing an abrupt, severe drop in hemoglobin with reticulocytopenia that can require transfusion.
- Prognosis
Excellent with appropriate management: most patients, particularly those with mild or moderate disease, have a normal life expectancy and good quality of life with folate supplementation and monitoring.
- Prevention
Vaccinate before elective splenectomy: pneumococcal, Haemophilus influenzae type b, and meningococcal vaccines (including serogroup B), completed at least 2 weeks before a planned, non-urgent splenectomy whenever feasible.
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