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Screening for   β  -thalassemia trait (BTT) relies on measuring hemoglobin (Hb) A 2 . Since multiple factors can affect HbA 2  levels, the screening can become unreliable. In 1356 healthy Arabs enrolled into a federally funded premarital BTT screening program, the effects of iron deficiency (ID),  α   + -thalassemia trait, gender, smoking, and tribalism on HbA 2  were studied. The complete blood count and hemoglobin fractions were determined on the entire cohort; serum ferritin (<15   μ  g/L) in 391 subjects was used to determine ID. BTT was present in 29 (2.1%) subjects (HbA 2  > 3.5%). Among 77(20.3%) subjects with ID, the mean HbA 2  (2.30 ± 0.23%) was 0.2% lower than in subjects without iron deficiency (2.50 ± 0.24%,  P  < 0.0001). In 65 (38%)/172 subjects with phenotypic  α   + -thalassemia trait, the mean HbA 2  (2.43 ± 0.24%) was 0.13% lower than in subjects without  α   + -thalassemia trait,  P  < 0.0001. The mean HbA 2  did not differ between males and females, smokers and nonsmokers, and between the tribes. Thus, 35 (2.6%) subjects with HbA 2  between 3.2 and 3.5% were at a risk of false negative diagnosis of BTT. Since iron deficiency and  α   + -thalassemia are both common and both lower HbA 2 , modifications in screening recommendations for BTT are proposed.

Hemoglobin A2 Lowered by Iron Deficiency and α-Thalassemia: Should Screening Recommendation for β-Thalassemia Change?

Hemoglobin A₂ Lowered by Iron Deficiency and α-Thalassemia: Should Screening Recommendation for β-Thalassemia Change?