Sickle Cell Trait Detection and Diagnosis

Primary Diagnostic Methods

The American Academy of Pediatrics recommends that 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 make a definitive diagnosis of sickle cell trait at birth, with a sensitivity and specificity of 99.5-100% compared to hemoglobin electrophoresis 1, 2, 3
Newborn screening has been routine since 1987 following National Institutes of Health recommendations, and results should be documented in the medical record and discussed with families at diagnosis, school entry, preadolescence, and transition to adult care 1, 2, 3, 4

Hemoglobin electrophoresis is the gold standard confirmatory test that separates and identifies different hemoglobin types, including HbA, HbS, HbC, and HbF, and can distinguish between sickle cell trait (HbAS: 55-65% HbA, 30-40% HbS) and sickle cell disease variants 1, 5

For individuals without prior newborn screening (born outside the U.S., immigrants, or pre-1987 births), the American Academy of Pediatrics recommends ordering hemoglobin electrophoresis directly as the initial test, which provides comprehensive hemoglobin phenotype information in a single test 1, 2, 3

When sickle cell trait is identified in a pregnant woman, the American College of Medical Genetics recommends that the baby's father must also be tested to determine if the fetus is at risk for sickle cell disease, with a 25% chance of having a child with sickle cell disease if both parents have sickle cell trait 6, 7
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, affecting measurement accuracy 8

The American Heart Association recommends that one should not rely solely on solubility testing for definitive diagnosis, as it cannot differentiate between trait (HbAS) and disease (HbSS, HbSC), and do not assume negative newborn screening in individuals born before 1987 or outside the U.S. - order confirmatory testing 1, 4

The American College of Cardiology is not mentioned, however, the NCAA uses solubility testing for screening athletes, but this is for initial detection only, not definitive diagnosis 9
For individuals with sickle cell trait requiring diabetes screening or monitoring, the American Diabetes Association recommends using an A1C assay without interference from hemoglobin variants, as sickle cell trait lowers A1C values by approximately 0.3% compared to individuals without the trait at the same glycemic level 10