How do you diagnose sickle cell anemia?

Diagnosis of Sickle Cell Anemia

The definitive diagnosis of sickle cell anemia requires a comprehensive hemoglobinopathy screen using high-performance liquid chromatography, capillary electrophoresis, mass spectrometry, or gel electrophoresis, which should be confirmed by a second test. 1

Diagnostic Testing Algorithm

Initial Screening

• Newborn screening programs detect sickle cell disease in infants, with screening now available in all 50 states, DC, Puerto Rico, US Virgin Islands, and US military 2
• For those without newborn screening results (e.g., born outside the US or before screening implementation), initial testing should be performed 2
• Hospital laboratories may use a rapid sickle solubility test to detect HbS, followed by a full hemoglobinopathy screen if positive 2

Confirmatory Testing

• A positive sickle solubility test alone is insufficient for diagnosis as it doesn't differentiate between heterozygous (trait), compound heterozygous, or homozygous (disease) states 1
• Hemoglobin electrophoresis is essential to confirm the presence and percentage of hemoglobin S and identify the specific genotype 1
• Four main genotypes exist: HbSS (most common), HbSC, Sβ⁰-thalassemia, and Sβ⁺-thalassemia, each with varying clinical severity 2

Additional Laboratory Evaluation

• Complete blood count (CBC) to assess for normocytic normochromic anemia 1
• Reticulocyte count to evaluate bone marrow response to hemolysis 1, 3
• Markers of hemolysis including bilirubin (total and direct) 1, 3
• Liver function tests (AST, ALT, alkaline phosphatase) 1, 3
• Renal function tests (BUN, creatinine) 1, 3

Interpretation of Results

Hemoglobin Patterns

• HbSS (sickle cell anemia): 80-95% HbS, 0% HbA, 5-15% HbF 2
• HbSC (sickle-C disease): 50-55% HbS, 0% HbA, 40-45% HbC 2
• Sβ⁰-thalassemia: 80-90% HbS, 0% HbA, 5-15% HbF 2
• Sβ⁺-thalassemia: 70-80% HbS, 10-25% HbA, <3% HbF 2
• Sickle trait (HbAS): 30-40% HbS, 55-65% HbA 2

Clinical Correlation

• Patients with HbSS and Sβ⁰-thalassemia typically have more severe disease manifestations 2
• HbSC and Sβ⁺-thalassemia generally have milder clinical presentations 2
• Each genotype shows marked variability in clinical expression and severity 2

Special Considerations

Timing of Diagnosis

• Infants with SCD are healthy at birth and develop symptoms as fetal hemoglobin declines 2
• First diagnostic visit should occur before 3 months of age 2
• Results should be discussed with parents and later with the child at school entry, preadolescence, and transition to adult care 2

Diagnostic Pitfalls to Avoid

• Using sickle solubility test alone for diagnosis, which can give false negative results in neonates or heavily transfused patients 1
• Failing to test siblings of affected children, who may also have disease or trait status 2
• Not communicating the diagnosis clearly on laboratory request forms, which may delay appropriate processing and interpretation 3
• Relying on spectral detection techniques without confirmatory testing, despite their potential as screening tools 4, 5

When to Suspect Sickle Cell Disease

• Unexplained severe atraumatic pain 6
• Normocytic anemia 6
• Acute illness with fever, pallor, or limping in a child with risk factors 2
• Family history of sickle cell disease or trait 2

Management Following Diagnosis

• Referral to a pediatric SCD center or hematologist for comprehensive care management 2
• Education of parents regarding disease course, complications, and genetic implications 2
• Establishment of baseline laboratory values for future comparison during acute events 2
• Implementation of preventive measures including penicillin prophylaxis and appropriate immunizations 2

By following this diagnostic approach, clinicians can accurately identify sickle cell anemia and its variants, allowing for appropriate management to reduce morbidity and mortality associated with this condition.