An 8-year-old girl, with a height and weight in the 10th percentile, presents with severe eye pain, scleral icterus, hepatomegaly, fever, tachycardia, and hypotension, along with laboratory findings of decreased haptoglobin and hemoglobin, what is the most likely diagnosis given her symptoms and lab results?

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Diagnosis: Hereditary Spherocytosis with Acute Hemolytic Crisis

This 8-year-old girl most likely has hereditary spherocytosis presenting with an acute hemolytic crisis, and the peripheral blood smear will show spherocytes. 1

Clinical Reasoning

The constellation of findings points definitively toward a hereditary hemolytic anemia rather than an acquired process:

  • Chronic hemolysis markers: Decreased haptoglobin and hemoglobin with scleral icterus indicate ongoing red cell destruction 1, 2, 3
  • Hepatomegaly: Reflects chronic hemolysis with splenic sequestration and compensatory extramedullary hematopoiesis 1
  • Growth failure: Height and weight at 10th percentile suggests chronic disease burden from hereditary hemolytic anemia 1
  • Young age with no prior diagnosis: Makes acquired causes like autoimmune hemolytic anemia or drug-induced hemolysis less likely 1

Why Spherocytes Are Most Likely

Spherocytes are the expected finding because hereditary spherocytosis is the most common hereditary hemolytic anemia presenting with these clinical features. 1, 2

Supporting Evidence for Spherocytes:

  • Hereditary spherocytosis characteristically presents with chronic hemolysis, splenomegaly, and spherocytes on peripheral smear 2
  • The American Society of Hematology guidelines emphasize that spherocytes with a family history and negative direct antiglobulin test are pathognomonic for hereditary spherocytosis 1, 2
  • Red cell morphology in membrane disorders like hereditary spherocytosis shows distinctive spherocytes, unlike enzyme deficiencies which show relatively normal morphology 4, 1

Why Not the Other Options:

High reticulocyte count alone is non-specific: While reticulocytosis occurs in hemolysis, it is paradoxically not as elevated as expected in hereditary hemolytic anemias before splenectomy because younger defective cells are preferentially sequestered in the spleen 4, 1. This creates a falsely reassuring reticulocyte response that doesn't reflect the true severity of hemolysis 1.

Pencil cells are incorrect: Pencil cells (elliptocytes) are characteristic of iron deficiency anemia or hereditary elliptocytosis, not the acute hemolytic presentation described here 2, 3. The presence of hepatomegaly, decreased haptoglobin, and scleral icterus rules out simple iron deficiency 1.

Diagnostic Workup

The American Journal of Hematology recommends this systematic approach for hereditary hemolytic anemia 4, 1:

  1. Peripheral blood smear: Will reveal spherocytes in hereditary spherocytosis 1, 2
  2. Direct antiglobulin test (DAT): Should be negative, excluding immune-mediated hemolysis 1, 2, 3
  3. Osmotic fragility test: Increased fragility confirms spherocytosis 4
  4. Family history: Often positive for anemia or splenectomy 1, 2

Critical Clinical Pitfall

Do not dismiss this as a simple viral illness despite the fever. The fever likely represents the acute hemolytic crisis triggered by a precipitating event (possibly the school activity mentioned), not a primary infectious process 4, 1. The severe eye pain may reflect bony pain from marrow expansion or referred pain from acute splenic sequestration 1.

The combination of chronic findings (growth failure, hepatomegaly) with acute decompensation (fever, severe pain, tachycardia) is classic for hereditary spherocytosis with superimposed hemolytic crisis 1, 2, 3.

References

Guideline

Hereditary Hemolytic Anemia Diagnosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Hemolytic anemia.

American family physician, 2004

Research

Hemolytic Anemia: Evaluation and Differential Diagnosis.

American family physician, 2018

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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