What diagnostic labs are used to diagnose sickle cell trait?

Diagnostic Labs for Sickle Cell Trait

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

Primary Diagnostic Approach

Newborn Screening (First-Line for Infants)

• 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 that can definitively diagnose sickle cell trait at birth, with sensitivity and specificity of 99.5-100% compared to hemoglobin electrophoresis. 1
• Newborn screening has been routine since 1987 and should 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

Confirmatory Testing Methods

Hemoglobin Electrophoresis (Gold Standard)

• Separates and identifies HbA, HbS, HbC, and HbF with high precision. 1
• Sickle cell trait shows characteristic pattern: 55-65% HbA and 30-40% HbS. 1
• Isoelectric focusing provides better resolution than conventional cellulose acetate electrophoresis at alkaline pH. 2

Alternative Laboratory Methods

• Cation exchange HPLC can be used as a first-line test in some laboratories. 2
• Solubility testing or electrophoresis on agar in citrate buffer should be used as confirmatory second tests, never as sole diagnostic methods. 2
• Quantitative hemoglobin electrophoresis at alkaline pH combined with citrate agar electrophoresis provides accurate definition. 3

Critical Clinical Pitfalls to Avoid

Do Not Rely on Solubility Testing Alone

• Solubility testing cannot differentiate between sickle cell trait (HbAS) and sickle cell disease (HbSS, HbSC), making it inadequate as a standalone diagnostic test. 1
• Always confirm with hemoglobin electrophoresis. 2

Do Not Assume Negative Screening in Certain Populations

• Never assume negative newborn screening in individuals born before 1987 or outside the U.S.—order confirmatory testing. 1

Special Testing Considerations

Partner Testing in Pregnancy

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

Impact on A1C Testing

• Sickle cell trait can lower A1C values by approximately 0.3% compared to individuals without the trait at the same glycemic level. 1, 4
• Some A1C assay methods experience interference from hemoglobin S variant, affecting measurement accuracy. 1, 4
• For patients with sickle cell trait requiring diabetes monitoring, use A1C assays without interference from hemoglobin variants, or use plasma glucose criteria instead. 4, 5

Point-of-Care Options for Resource-Limited Settings

• HemoTypeSC, a point-of-care immunoassay, demonstrated 99.5% sensitivity and 99.9% specificity across all hemoglobin phenotypes in multi-center evaluation. 6
• This rapid test costs less than $2 per test and can provide timely diagnosis in resource-limited regions. 6