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

Abstract

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.