The Effect of Co‐Existing Iron Deficiency on HbA2 Level and the Diagnosis of Beta Thalassemia Trait

Introduction The diagnosis of beta thalassemia trait is primarily based on an elevated HbA2 level (> 3.5%) measured by high‐performance liquid chromatography or capillary electrophoresis. Iron deficiency (ID) can influence HbA2 levels, raising concern about potential diagnostic misclassification, particularly in individuals with borderline HbA2 values. This study aimed to evaluate the effect of ID and its correction on HbA2 levels and the diagnosis of beta thalassemia trait. Methods A prospective interventional study conducted between June 2021 and June 2022 at a National Thalassemia Centre, Sri Lanka. Ninety‐two participants aged 12–57 years with low red cell indices (MCV ≤ 80 fL, MCH ≤ 27 pg) and HbA2 < 3.5% were included. All had serum ferritin < 30 ng/mL indicating ID. Hematological and iron parameters, including HbA2 levels, were assessed before and after 3 months of oral iron therapy. Comparisons were made between subgroups with serum ferritin levels of < 15 ng/mL and 15–30 ng/mL. Correlations between Hb, HbA2, ferritin, and other iron indices were also examined. Results A significant positive correlation was observed between Hb and HbA2 levels prior to treatment. Following iron therapy, HbA2 levels increased significantly in iron‐deficient individuals ( p < 0.001). In three of eight participants with borderline HbA2 levels, treatment raised HbA2 above the 3.5% diagnostic threshold. Conclusions Oral iron therapy significantly affects HbA2 levels in iron‐deficient individuals and may cause borderline values to cross the diagnostic threshold for beta thalassemia trait. Iron status should therefore be considered when interpreting HbA2 results in thalassemia screening.