Is HbA2 level a reliable diagnostic measurement for β-thalassemia trait in people with iron deficiency?

Abstract

Microcytic anemia is commonly caused by either iron deficiency, β-thalassemia trait (BTT) or a-thalassemia trait. Elevated HbA 2 level (=3.5%) is a well-established screening test for BTT [1]. Conflicting reports have led to confusion about the reliability of this test to screen for BTT in the presence of iron deficiency. In this study, 444 people with BTT were confirmed by DNA-based genotyping. HbA 2 levels were assessed by high performance liquid chromatography (HPLC). Individuals were classified as 'iron-deficient' or 'non-iron-deficient' based on serum ferritin level. The mean HbA 2 (5.3%) in individuals with serum ferritin <15 μg/L was lower than those who are not iron-deficient (5.6%; P = 0.004). Nevertheless, HbA 2 in individuals with serum ferritin <15 μg/L ranged from 4.2 to 6.2%, with none <3.5%. Multiple linear-regression analysis revealed a significant association of lower HbA 2 with β +-thalassemia mutation and serum ferritin <15 μg/L. Thus, in this large cohort of individuals with BTT, serum ferritin <15 μg/L was associated with a small decrease in HbA 2. Nonetheless, individuals with overt iron deficiency and BTT consistently had elevated HbA 2 (=3.5%) indicating that HbA 2 remains a reliable test for BTT screening in the presence of iron deficiency. © 2011 Wiley Periodicals, Inc.