Hereditary Spherocytosis
The most likely diagnosis is C. Hereditary spherocytosis (HS), based on the pathognomonic finding of microspherocytes on peripheral blood smear combined with hemolytic anemia, splenomegaly, and jaundice in a young child.
Clinical Reasoning
This 5-year-old girl presents with the classic triad of HS:
- Anemia with hemolytic features: Low hemoglobin (82 g/L) with markedly elevated reticulocytes (9%), indicating compensatory bone marrow response to ongoing hemolysis 1, 2
- Jaundice: Reflecting indirect hyperbilirubinemia from red cell destruction 1, 3
- Splenomegaly: 4 cm enlargement consistent with chronic hemolysis and splenic sequestration of abnormal spherocytes 1, 4
Diagnostic Blood Smear Findings
The peripheral blood smear is diagnostic:
- Microspherocytes (++): This is the pathognomonic finding for HS, representing red cells with defective membrane skeleton proteins (spectrin deficiency) that lose membrane surface area and assume a spherical shape 1, 2
- Mild anisocytosis: Common in HS due to variable degrees of membrane loss 2
- Normal MCV (80 fL): Despite being called "microspherocytes," the MCV is typically normal or only slightly reduced in HS, distinguishing it from true microcytic anemias 2
Why Not the Other Options?
A. Biliary obstruction would cause conjugated hyperbilirubinemia with elevated direct bilirubin, not the hemolytic pattern seen here with reticulocytosis and spherocytes 5
B. Sickle cell anemia presents with sickle cells (drepanocytes) on blood smear, not spherocytes, and typically shows more severe anemia with vaso-occlusive crises 5
D. Autoimmune hemolytic anemia (AIHA) can produce spherocytes, but would require a positive direct antiglobulin test (Coombs test) to confirm antibody-mediated hemolysis 1, 4. HS is distinguished by a negative Coombs test 2, 4
Confirmatory Testing
To definitively confirm HS diagnosis:
- Osmotic fragility test: Increased fragility in both fresh (0.48 g/dL) and incubated blood (0.65 g/dL) is characteristic 2
- Autohemolysis test: Markedly increased (average 15.54%) but corrected by glucose addition (to 4.07%) 2
- Genetic testing: Mutations in ANK1, SPTB, SPTA1, SLC4A1, or EPB42 genes confirm the diagnosis, with SPTB and ANK1 being most common 3
Clinical Pitfalls
Critical caveat: Always perform a direct antiglobulin test (Coombs test) to exclude AIHA, as both conditions can present with spherocytes and hemolysis 1, 4. The negative Coombs test is essential for diagnosing HS over AIHA.
The elevated MCH (39 pg/cell) reflects the spherocytic shape with concentrated hemoglobin content despite normal cell volume, which is characteristic of membrane disorders rather than hemoglobinopathies 2.