What is the recommended approach for screening for sickle cell anemia?

Screening for Sickle Cell Anemia

All patients at risk of sickle cell disease should be screened before surgery, unless they are ethnically of solely northern or eastern European, Jewish or South-East Asian heritage, or have been previously screened. 1

Who Should Be Screened

Screening for sickle cell anemia should follow a targeted approach based on risk factors:

• Universal newborn screening: All newborns should be screened as part of established newborn screening programs, which are now implemented in many countries 1, 2
• Pre-operative screening: All patients at risk should be screened before surgery, but repeated unnecessary screening should be avoided 1
• Risk-based screening: Screening should target individuals with:
  • African, Mediterranean, Middle Eastern, Indian, or Caribbean ancestry
  • Family history of sickle cell disease or trait
  • Unexplained severe atraumatic pain or normocytic anemia 2

Screening Methods

The recommended screening approach follows a systematic process:

1. Initial screening tests:

   • Newborns: Isoelectrofocusing or high-performance liquid chromatography of dried blood spots 3
   • Older children/adults: Hospital laboratories typically use one of two approaches:
     • Rapid sickle solubility test followed by full hemoglobinopathy screen if positive
     • Direct full hemoglobinopathy screen using high-performance liquid chromatography, capillary electrophoresis, mass spectrometry, or gel electrophoresis 1

2. Important caution: A positive sickle solubility test should never be used in isolation as it:

   • Cannot differentiate between heterozygous, compound heterozygous, or homozygous states
   • Can give false negative results in neonates or heavily transfused patients 1
   • May miss compound heterozygous states like SC disease 4

Timing of Screening

• Newborn period: Optimal time for initial screening as part of established newborn screening programs 1, 2
• Pre-operative: Before any surgical procedure for at-risk patients not previously screened 1
• Targeted screening during pregnancy: While sometimes practiced in West African areas, this approach is insufficient as it can miss approximately 1 in 6 affected newborns 4

Follow-up After Positive Screening

For positive screening results:

1. Confirmatory testing: Full hemoglobinopathy screen to determine exact genotype (HbSS, HbSC, Sβ⁰-thalassemia, or Sβ⁺-thalassemia) 1

2. Referral: Consultation with pediatric hematologist or sickle cell center before 3 months of age 1

3. Documentation: Record hemoglobinopathy results (disease, trait, or normal) in the medical record 1

4. Family education: Educate parents about:

   • Disease implications and management
   • Genetic implications for future pregnancies
   • Need to test siblings 1

5. Preventive care initiation:

   • Penicillin prophylaxis
   • Pneumococcal immunization
   • Malaria prevention in endemic areas 3

Clinical Pitfalls to Avoid

• Relying solely on sickling tests: This can miss compound heterozygous states like SC disease 4
• Delaying screening until symptoms appear: Early mortality is high without preventive interventions 3, 5
• Failing to screen siblings: All siblings of affected children should be tested 1
• Missing high-risk patients: In areas without universal newborn screening, consider screening all children with severe anemia (Hb < 6 g/dL) 5
• Inadequate follow-up: Effective contact and retrieval systems are essential to ensure affected infants receive care 3

Implementing comprehensive screening programs, particularly in high-prevalence regions like sub-Saharan Africa, can significantly reduce mortality and morbidity from sickle cell disease through early identification and preventive care 3, 6.