Hemoglobin A(2) Lowered by Iron Deficiency and α-Thalassemia: Should Screening Recommendation for β-Thalassemia Change?

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 μg/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.