What lab test is used to confirm a diagnosis of sickle cell trait?

Confirmatory Testing for Sickle Cell Trait

Hemoglobin electrophoresis is the gold standard confirmatory test for sickle cell trait, which separates and identifies different hemoglobin types and can definitively distinguish sickle cell trait (HbAS: 55-65% HbA, 30-40% HbS) from sickle cell disease variants. 1

Primary Diagnostic Approach

For Individuals Born in the U.S. After 1987

• Check existing 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 compared to hemoglobin electrophoresis 1
• These results should already be documented in the medical record 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
• This provides comprehensive hemoglobin phenotype information in a single test without requiring preliminary screening 1

Technical Specifications of Hemoglobin Electrophoresis

The test identifies and quantifies:

• HbA (normal adult hemoglobin): 55-65% in sickle cell trait 1
• HbS (sickle hemoglobin): 30-40% in sickle cell trait 1
• HbC, HbF, and other variants for comprehensive phenotyping 1

This pattern definitively distinguishes trait (HbAS) from disease states (HbSS, HbSC, HbS-beta thalassemia) 1

Critical Pitfalls to Avoid

Do Not Rely on Solubility Testing Alone

• Solubility testing (sickle cell preparation) cannot differentiate between sickle cell trait and sickle cell disease 1
• While solubility tests detect the presence of HbS, they cannot quantify the proportion of HbS versus HbA, which is essential for distinguishing trait from disease 2, 3
• The NCAA uses solubility testing for screening athletes, but this is for initial detection only, not definitive diagnosis 4

Do Not Assume Negative Screening in Certain Populations

• Never assume individuals born before 1987 or outside the U.S. have been screened 1
• Order confirmatory hemoglobin electrophoresis in these populations regardless of clinical presentation 1

Special Clinical Considerations

Pregnancy and Genetic Counseling

• When sickle cell trait is identified in a pregnant woman, the baby's father must also be tested to determine fetal risk 1
• If both parents have sickle cell trait, there is a 25% chance of having a child with sickle cell disease 1

Impact on Other Laboratory Tests

• Sickle cell trait lowers A1C values by approximately 0.3% compared to individuals without the trait at the same glycemic level 1
• Some A1C assay methods experience interference from the hemoglobin S variant 1
• For individuals with sickle cell trait requiring diabetes screening or monitoring, use an A1C assay without interference from hemoglobin variants (updated list available at ngsp.org/interf.asp) 4

Alternative Testing Methods

While hemoglobin electrophoresis remains the gold standard, other methods include:

• Isoelectric focusing: Provides similar diagnostic accuracy 3
• Cation exchange HPLC: Increasingly used and highly accurate 3
• Point-of-care immunoassays (e.g., HemoTypeSC): Show 99.5% sensitivity and 99.9% specificity but are primarily used in resource-limited settings 5

However, any positive screening test should be confirmed with hemoglobin electrophoresis for definitive diagnosis and accurate phenotyping 3