What laboratory test do you order to diagnose sickle cell trait (SCT)?

Laboratory Testing for Sickle Cell Trait

Order hemoglobin electrophoresis as the gold standard confirmatory test to diagnose sickle cell trait, which will show 55-65% HbA and 30-40% HbS. 1

Primary Diagnostic Approach

For Individuals Born in the U.S. After 1987

• Check the newborn screening results first, as all 50 U.S. states, the District of Columbia, Puerto Rico, the U.S. Virgin Islands, and the U.S. military perform universal newborn screening for hemoglobinopathies with 99.5-100% sensitivity and specificity. 1
• If newborn screening documented sickle cell trait, no additional testing is needed unless clinical confirmation is required. 1

For Individuals Without Prior Newborn Screening

• Order hemoglobin electrophoresis directly as the initial test for individuals born outside the U.S., immigrants, or those born before 1987. 1
• Hemoglobin electrophoresis separates and identifies different hemoglobin types (HbA, HbS, HbC, HbF) and definitively distinguishes sickle cell trait (HbAS) from sickle cell disease variants (HbSS, HbSC). 1

Confirmatory Testing Requirements

Never rely on a single test alone for diagnosis. 2, 3

• If hemoglobin electrophoresis is performed first, confirm with a second test such as:

  • Sickle solubility test 2, 3
  • Electrophoresis on agar in citrate buffer 3

• Alternative comprehensive screening methods include high-performance liquid chromatography (HPLC), capillary electrophoresis, mass spectrometry, or gel electrophoresis. 2

Critical Pitfalls to Avoid

• Do not use solubility testing alone for definitive diagnosis, as it cannot differentiate between sickle cell trait (HbAS) and sickle cell disease (HbSS, HbSC). 1, 4
• Do not assume negative newborn screening in individuals born before 1987 or outside the U.S.—always order confirmatory testing. 1
• A positive sickle solubility test should never be used in isolation as it doesn't differentiate between heterozygous, compound heterozygous, or homozygous states. 2

Special Clinical Contexts

Pregnancy Screening

• When sickle cell trait is identified in a pregnant woman, the baby's father must also be tested to determine if the fetus is at risk for sickle cell disease (25% chance if both parents have trait). 1

Point-of-Care Options

• Newer point-of-care tests like Sickle SCAN and HemoTypeSC show 99.5-100% sensitivity and specificity for detecting hemoglobin S, useful in resource-limited settings or for rapid screening. 5, 6
• These should still be confirmed with hemoglobin electrophoresis for definitive diagnosis. 2

Diabetes Monitoring Consideration

• Be aware that sickle cell trait can lower A1C values by approximately 0.3% compared to individuals without the trait at the same glycemic level, and some A1C assay methods experience interference from hemoglobin S variant. 1