What is the approach to managing a patient, potentially a pediatric or young adult, presenting with microspherocytes, suspected of having hereditary spherocytosis or other hemolytic anemias?

Management of Microspherocytes and Suspected Hereditary Spherocytosis

Diagnostic Confirmation

When microspherocytes are identified on peripheral blood smear, the priority is to confirm hereditary spherocytosis (HS) through specific testing while simultaneously assessing disease severity and complications.

Essential Diagnostic Tests

• Eosin-5-maleimide (EMA) binding test is the preferred confirmatory test for HS, with superior sensitivity and specificity compared to traditional osmotic fragility testing 1
• Osmotic fragility testing (both fresh and incubated blood) remains useful when EMA testing is unavailable, with median osmotic fragility typically increased to 0.48 g/dL (fresh) and 0.65 g/dL (incubated) in HS patients 2
• The Acidified Glycerol Lysis Time (AGLT) test serves as an alternative confirmatory test 1
• Complete blood count typically reveals microcytic anemia (mean Hb in children: 10.5 g/dL; adults: 10.6-13.2 g/dL depending on sex) with marked reticulocytosis (average 336 x 10⁹/L) 2
• Indirect bilirubin and LDH are characteristically elevated (average 36.25 mmol/L and 236.48 UI/L respectively), with 76.5% of children and 26.7% of adults showing absent haptoglobin 2

Critical Diagnostic Pitfalls

• Do not rely solely on spherocyte visualization—microspherocytes may be sparse or absent during acute hemolytic crises, particularly when complicated by folate deficiency 3
• Negative Coombs test is essential to distinguish HS from autoimmune hemolytic anemia 2
• When classical features are absent on blood film or osmotic fragility testing, genetic analysis for mutations in SPTA1, SPTB, ANK1, SLC4A1, or EPB42 genes may be necessary, particularly in severe cases requiring early transfusions 4

Assessment of Disease Severity

Stratification Based on Clinical Presentation

• Mild HS: Compensated hemolysis, Hb >11 g/dL, minimal symptoms
• Moderate HS: Hb 8-11 g/dL, intermittent jaundice, splenomegaly
• Severe HS: Hb <8 g/dL, transfusion-dependent, early childhood presentation 1, 5

Screening for Complications

• Obtain abdominal ultrasound to screen for gallstones, as the risk of pigment cholelithiasis increases with age and is directly related to chronic hemolysis 5
• Screen for folate deficiency with serum folate levels, as chronic hemolysis increases folate consumption and can precipitate megaloblastic crisis 3
• Assess for secondary hemochromatosis in transfusion-dependent patients 4

Treatment Algorithm

Medical Management

• Initiate daily folic acid supplementation (1 mg daily) in all patients with confirmed HS to prevent megaloblastic crisis due to increased folate consumption from chronic hemolysis 3
• Monitor hemoglobin, reticulocyte count, and bilirubin every 3-6 months to assess hemolysis severity 2
• Transfusion support is reserved for severe anemia (Hb <7 g/dL) or hemolytic crises 4

Surgical Management: Splenectomy Indications

Splenectomy is indicated in virtually all patients with moderate to severe HS, as it provides clinical cure of anemia in most cases 5

Timing of Splenectomy

• Delay splenectomy until after 6 years of age whenever possible to minimize the risk of overwhelming post-splenectomy sepsis (OPSI) 5
• In severe cases requiring frequent transfusions before age 6, consider partial splenectomy as an alternative to preserve some splenic immunologic function while reducing hemolysis 1
• Patients with mild, compensated HS may not require splenectomy 1

Surgical Considerations

• Perform thorough intraoperative search for accessory spleens and remove them, as retained accessory splenic tissue can lead to recurrent hemolysis 5
• If gallstones are present at the time of splenectomy, perform concurrent cholecystectomy 5
• Prophylactic cholecystectomy is not indicated if gallstones are absent 5

Post-Splenectomy Management

• Administer pneumococcal, meningococcal, and Haemophilus influenzae type b vaccines at least 2 weeks before splenectomy 1
• Provide lifelong penicillin prophylaxis or educate patients about early antibiotic use for febrile illness to prevent OPSI 1
• Spherocytosis persists on blood smear post-splenectomy, but hemolysis is alleviated and anemia is corrected in most patients 5

Special Populations

• Patients with recessively inherited HS (compound heterozygous mutations) experience significant benefit from splenectomy but may not achieve complete correction of anemia 4, 5
• These patients may continue to require occasional transfusions despite splenectomy 5

Family Screening

• Obtain detailed family history, as HS typically follows autosomal dominant inheritance (though 12-25% have negative family history due to de novo mutations) 2
• Screen first-degree relatives with CBC, reticulocyte count, and blood smear examination 2
• Genetic counseling is appropriate for families with identified mutations, particularly for severe phenotypes 4