What is the diagnosis for a 10-year-old female patient presenting with pallor, splenomegaly, a total leukocyte count (TLC) of 30,000, severe anemia with a hemoglobin level of 5.6, no lymphadenopathy, elevated serum glutamic-pyruvic transaminase (SGPT) of 51, total serum bilirubin of 4.6 with unconjugated bilirubin of 3.6?

Diagnosis: Hereditary Spherocytosis with Hemolytic Crisis

Based on the clinical presentation of a 10-year-old with severe anemia (Hb 5.6 g/dL), marked splenomegaly, leukocytosis (TLC 30,000), predominantly unconjugated hyperbilirubinemia (3.6 mg/dL unconjugated of 4.6 mg/dL total), and absence of lymphadenopathy, the most likely diagnosis is hereditary spherocytosis in hemolytic crisis. 1, 2, 3

Key Diagnostic Features Supporting This Diagnosis

Pattern of Hemolysis

• Predominantly unconjugated hyperbilirubinemia (78% unconjugated) indicates extravascular hemolysis, which is characteristic of hereditary red cell membrane disorders rather than intrahepatic cholestasis or biliary obstruction 4, 2, 5
• The elevated unconjugated bilirubin results from breakdown of hemoglobin by the reticuloendothelial system, primarily in the spleen 4
• Splenomegaly is present in approximately 80% of patients with chronic hereditary hemolytic anemias and reflects the site of red cell destruction 4, 3

Clinical Presentation Consistent with Membranopathy

• Pallor, anemia, splenomegaly, and jaundice form the classic tetrad of congenital hemolytic anemia 3
• The absence of lymphadenopathy argues strongly against lymphoproliferative disorders (leukemia, lymphoma) or storage diseases, which typically present with generalized lymphadenopathy 1, 6
• Leukocytosis (TLC 30,000) represents a physiologic bone marrow response to severe anemia rather than a primary hematologic malignancy 1

Age and Severity Pattern

• Presentation at age 10 with severe manifestations is consistent with hereditary spherocytosis, which can present at any age from infancy through adolescence 4, 3
• The severity of anemia (Hb 5.6 g/dL) suggests either a hemolytic crisis (often triggered by viral infection) or chronic severe disease 4, 7

Essential Confirmatory Testing Required

Immediate Laboratory Studies

• Peripheral blood smear examination to identify spherocytes - this is the single most important diagnostic test and should never be skipped in any child with splenomegaly and anemia 1, 8, 5
• Reticulocyte count - should be markedly elevated (typically >5-10%) indicating bone marrow compensation for hemolysis 2, 5, 9
• Lactate dehydrogenase (LDH) - will be elevated as a marker of hemolysis 2, 5, 9
• Haptoglobin - will be decreased or undetectable due to binding of free hemoglobin 2, 5, 9
• Direct antiglobulin test (Coombs test) - must be negative to exclude autoimmune hemolytic anemia 4, 2, 5

Specialized Testing

• Osmotic fragility test or eosin-5-maleimide (EMA) binding test - confirms hereditary spherocytosis by demonstrating increased red cell membrane fragility 3
• Abdominal ultrasound - to confirm splenomegaly, assess splenic volume, and evaluate for gallstones (common complication) 1, 8

Critical Differential Diagnoses to Exclude

Malignant Causes (Must Be Ruled Out Urgently)

• Chronic myeloid leukemia (CML) can present with marked splenomegaly and leukocytosis in children, but typically shows circulating blasts on peripheral smear and requires BCR::ABL1 testing 1, 6
• Acute lymphoblastic leukemia (ALL) presents with lymphadenopathy in 20% of cases, which is absent here 6
• The peripheral blood smear will definitively exclude leukemia by absence of blasts 1, 8

Other Hemolytic Anemias

• Pyruvate kinase deficiency presents similarly with chronic hemolysis, splenomegaly, and unconjugated hyperbilirubinemia, but is distinguished by normal red cell morphology on smear and requires enzyme assay for diagnosis 4
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency causes episodic rather than chronic hemolysis and is triggered by oxidative stress 2, 5
• Autoimmune hemolytic anemia (AIHA) is excluded by negative direct antiglobulin test 4, 2

Storage Disorders (Less Likely Given Age and Presentation)

• Acid sphingomyelinase deficiency (Niemann-Pick) typically presents before age 6 with failure to thrive, and would show characteristic foam cells on bone marrow examination 1, 6
• The absence of developmental delay or neurologic symptoms argues against storage disorders 1

Interpretation of Liver Function Abnormalities

• Mildly elevated SGPT (51 U/L) is common in chronic hemolytic states due to hepatic congestion from splenomegaly and does not indicate primary liver disease 4
• The pattern of predominantly unconjugated hyperbilirubinemia (78% unconjugated) definitively excludes hepatocellular disease or biliary obstruction as primary causes 4
• Gilbert syndrome co-inheritance can exacerbate hyperbilirubinemia in hereditary spherocytosis but does not change management 4

Management Implications

Immediate Management

• Avoid transfusion to hemoglobin >10 g/dL as sequestered red cells in the enlarged spleen may be acutely released causing overtransfusion 1
• Transfuse packed red blood cells cautiously to hemoglobin 7-8 g/dL if symptomatic 1
• Evaluate for precipitating factors (viral infection, particularly parvovirus B19 which causes aplastic crisis) 4, 3

Definitive Treatment Considerations

• Splenectomy is curative for hereditary spherocytosis, typically resulting in hemoglobin increase of 1-3 g/dL and elimination of transfusion requirements 4, 3
• Splenectomy should be deferred until after age 5-6 years when possible to reduce infection risk 4
• Pre-splenectomy vaccination (pneumococcal, meningococcal, Haemophilus influenzae type b) is mandatory 4

Long-term Monitoring

• Monitor for gallstone formation with periodic ultrasound, as cholelithiasis develops in most patients by adolescence due to chronic hyperbilirubinemia 4, 7, 3
• Cholecystectomy can be performed concurrently with splenectomy if gallstones are present 7, 3
• Monitor iron status, as iron overload can occur even without transfusions in chronic hemolytic states 4

Common Pitfalls to Avoid

• Do not assume immune thrombocytopenic purpura (ITP) if thrombocytopenia is present, as significant splenomegaly suggests an alternative diagnosis 8
• Do not miss the peripheral smear examination - this is the most critical diagnostic step and directly visualizes spherocytes 1, 8, 5
• Do not perform splenectomy without confirming the diagnosis, as splenectomy is contraindicated in some other hemolytic conditions like hereditary stomatocytosis due to thrombotic risk 4
• Do not attribute all hyperbilirubinemia to Gilbert syndrome without excluding hemolysis, as the unconjugated fraction can be elevated in both conditions 4