What is the diagnosis and treatment for a patient with suspected hereditary spherocytosis?

Hereditary Spherocytosis: Diagnosis and Treatment

Diagnostic Approach

For suspected hereditary spherocytosis, combine flow cytometric osmotic fragility testing (FOFT) with eosin-5'-maleimide (EMA) dye-binding test to achieve 100% diagnostic sensitivity. 1

Initial Clinical Assessment

• Look specifically for the classic triad: anemia, jaundice, and splenomegaly 2
• Examine peripheral blood smear for spherocytes (small, dense, round red blood cells lacking central pallor) 2, 3
• Obtain complete blood count showing anemia with elevated reticulocyte count (indicating compensatory hemolysis) 2
• Note that patients may present without anemia but with severe jaundice and cholestasis, particularly in late-stage disease 3

Definitive Diagnostic Testing

The American Society of Hematology recommends combining FOFT with EMA dye-binding test for optimal diagnostic accuracy. 1

• FOFT has 96.6% sensitivity and 98.63% specificity, significantly outperforming conventional osmotic fragility testing 1
• Use extended 300-second analysis time in FOFT for optimal sensitivity (90%) in pediatric populations 1
• EMA binding test by flow cytometry provides confirmatory diagnosis 3

Important Diagnostic Pitfalls

• Conventional osmotic fragility testing is unreliable: reticulocytosis makes young red cells more resistant to osmotic stress, potentially yielding false-negative results 1
• Recent blood transfusions interfere with test interpretation and should delay testing 1
• Red cell osmotic fragility can be normal in other red cell enzyme deficiencies, making it non-specific 1

Genetic Confirmation

• Genetic analysis identifies mutations in spectrin genes (SPTA1, SPTB) or other membrane protein genes 4
• Consider genetic testing when classical features are absent on blood film or when family screening is needed 4, 3
• Novel mutations may determine disease severity, particularly compound heterozygous states 4

Treatment Strategy

Indications for Splenectomy

Splenectomy is indicated in virtually every patient with moderate to severe hereditary spherocytosis and should be performed after age 6 years to minimize infection risk. 5

• Moderate to severe forms with transfusion dependence require splenectomy 2, 5
• Patients requiring monthly transfusions since infancy are clear candidates 4
• Delay splenectomy until after 6 years of age when possible to reduce overwhelming post-splenectomy sepsis risk 5

Surgical Considerations

• At the time of splenectomy, identify and remove any accessory spleens to prevent recurrent hemolysis 5
• If gallstones are present, perform concurrent cholecystectomy since pigment gallstones are common (risk increases with age, uncommon before age 10) 5
• Consider partial splenectomy as an alternative to retain splenic immunologic function while decreasing hemolysis rate 2

Expected Outcomes

• Splenectomy achieves clinical cure of anemia in most patients, though spherocytosis persists 5
• Hemolysis is alleviated, reducing transfusion requirements and risk of future gallstone formation 5
• Post-splenectomy, anemia improves and transfusion requirements steadily reduce 4
• Exception: Patients with recessively inherited spherocytosis benefit significantly but anemia is not completely corrected 5

Post-Splenectomy Management

• Life-long risk of potentially lethal infections requires vaccination and antibiotic prophylaxis 2
• Monitor for secondary complications including hemochromatosis from chronic hemolysis 6
• Screen for iron overload even without genetic hemochromatosis mutations, as idiopathic hemochromatosis can develop in long-standing HS 6

Management of Complications

• Address secondary hemochromatosis if present (elevated ferritin, transferrin saturation) 6
• Monitor for development of red blood cell antibodies in transfusion-dependent patients 4
• Manage gallstones surgically when symptomatic or at time of splenectomy 5