HBA2 levels in iron deficiency - Can iron deficiency mask thalassemia screening?

Iron deficiency has been found to affect hemoglobin A2 (HbA2) values in HPLC. This can be an issue for thalassemia screening laboratories where there is heavy reliance on increased Hb A2 levels for diagnosis of heterozygous thalassemia state. In resource constrained countries like India this could be real challenging where iron deficiency is widespread and facilities for molecular confirmation in borderline HbA2 values is generally unavailable. It was a prospective study done in a tertiary care center over 18 months. All consecutive patients (n = 164) presenting with microcytic hypochromic anemia on peripheral smear were included for further investigations out of which 92 were found to have pure iron deficiency (Hb < 12 Gm/dL with ferritin less than12 ng/ml) on iron parameters. These patients were divided into two groups, Group A with Hb < 9 g/dl and Group B with Hb > 9 g/dl. Common hematological parameters, iron indices and HbA2 levels were analysed in these two group of patients at baseline and after 3 months of documented oral iron therapy. Chi-square and Pearson tests were used for statistical analysis and a P- value of < 0.05 was considered statistically significant. As expected iron deficiency was found more prevalent in females (72%) than in males(28%). Mean pre -treatment and post - treatment hemoglobin of patients in group A was 8±0.5 gm/dl and 11.3±1.1gm/dl respectively and in group B was 10.2±0.6 g/dl and 11.5±1 g/dl showing positive correlation. Mean pre treatment and post treatment HbA2 levels of patients in group A were 1.8±0.5% and 2.4±0.5% respectively showing statistically significant change after iron therapy (P< 0.0001) but mean pre treatment and post treatment HbA2 levels of patients in group B were 2.1±0.4% and 2.2±0.5% respectively . this change post therapy was statistically insignificant(P=0.1517). The change in HbA2 levels was statistically insignificant for patients with mild / moderate iron deficiency anemia (Hb > 9 Gm/DL). Thus diagnosis of β thalassemia trait will not be difficult in patients with concomitant mild iron deficiency anemia but patients with severe iron deficiency anemia should first be treated with iron supplements for correct diagnosis of β Thalassemia trait especially patients with borderline Hb A2 levels.