What is the best course of action for an 18-month-old child with a history of pallor and irregularity, who presented with shortness of breath and severe anemia, with a hemoglobin level of less than 70 g/L, normal white blood cell count, and previous episodes of hand-foot syndrome in infancy?

Hemoglobin Electrophoresis is the Best Initial Diagnostic Test

For an 18-month-old child with severe anemia (Hg <70 g/L), history of hand-foot syndrome in infancy, pallor, irritability, shortness of breath, and normal WBC count, hemoglobin electrophoresis (Option B) should be performed first to diagnose sickle cell disease.

Clinical Reasoning

Why Hemoglobin Electrophoresis is the Priority

The clinical presentation strongly suggests sickle cell disease (SCD):

• Hand-foot syndrome (dactylitis) in infancy is a hallmark early manifestation of sickle cell disease, typically occurring between 6 months and 2 years of age 1
• Severe anemia with Hg <70 g/L is consistent with chronic hemolytic anemia seen in SCD 1
• Normal WBC count helps distinguish this from acute infection or leukemia
• Shortness of breath indicates the child is symptomatic from severe anemia, which in SCD patients warrants urgent evaluation 1

Diagnostic Algorithm

Step 1: Hemoglobin Electrophoresis

• This test definitively identifies hemoglobin variants (HbSS, HbSC, HbS-beta thalassemia) and confirms sickle cell disease 1
• Should be performed urgently given the severity of presentation 1

Step 2: Complete Blood Count with Reticulocyte Count

• Reticulocyte count will be elevated in hemolytic anemia, confirming active hemolysis 2
• Helps differentiate from hypoproliferative causes 3

Step 3: Additional Hemolysis Markers (if needed)

• LDH, unconjugated bilirubin, and haptoglobin can confirm hemolysis 2
• However, these are supportive rather than diagnostic for the underlying cause 2

Why NOT the Other Options

LDH (Option A) - Not Specific Enough

• While LDH is elevated in hemolysis, it is non-specific and does not identify the underlying cause 2
• It confirms hemolysis is occurring but doesn't distinguish between sickle cell disease, G6PD deficiency, hereditary spherocytosis, or other hemolytic anemias 2
• Should be obtained as part of hemolysis workup but is not the primary diagnostic test 2

Coombs Test (Option C) - Wrong Mechanism

• Direct antiglobulin test (Coombs) identifies immune-mediated hemolytic anemia 2
• The clinical history of hand-foot syndrome in infancy points to a hemoglobinopathy, not immune hemolysis 1
• Coombs test would be negative in sickle cell disease 2
• This test is appropriate when autoimmune hemolytic anemia is suspected, not for hemoglobinopathies 2

Immediate Management Considerations

Transfusion Decision

• Hemoglobin <70 g/L with symptoms (shortness of breath) may require transfusion 1
• In sickle cell disease, transfusion decisions should consider clinical stability, not just hemoglobin level 1
• The presence of respiratory symptoms and severe anemia warrants careful evaluation for acute chest syndrome 1
• Transfuse to hemoglobin ~100 g/L if symptomatic, avoiding overtransfusion above 100 g/L 1

Acute Complications to Rule Out

• Splenic sequestration: rapidly enlarging spleen with acute drop in hemoglobin >20 g/L from baseline 1
• Acute chest syndrome: new pulmonary infiltrate with respiratory symptoms 1
• Aplastic crisis: low reticulocyte count with worsening anemia, often from parvovirus B19 1

Common Pitfalls to Avoid

• Do not delay hemoglobin electrophoresis while waiting for other test results in a child with this classic presentation 1
• Do not assume iron deficiency anemia based solely on severe anemia and pallor—the history of hand-foot syndrome is pathognomonic for SCD 1
• Do not order Coombs test first when the clinical picture suggests hemoglobinopathy rather than immune hemolysis 2
• Avoid acute overtransfusion in potential splenic sequestration, as sequestered cells may be released causing sudden hemoglobin rise 1
• Check spleen size urgently as splenic sequestration can progress rapidly to shock and death 1