HbA2 levels in children with β-thalassemia trait associated with iron deficiency: A perspective for pediatricians.

Abstract

Objectives: A critical factor in β-thalassemia trait screening is a hemoglobin A2 (HbA2) level of 3.5% or higher. In children with iron deficiency, HbA2 levels decrease, and diagnosis may be missed. Studies with adult carriers have yielded conflicting results on this issue. The effectiveness of HbA2-based thalassemia screening in carrier children with iron deficiency has not been studied before.

Methods: In this study, among 213 children with β-thalassemia trait, those with iron deficiency were determined based on ferritin value (<15 ng/mL), and their HbA2 levels were examined. We compared HbA2 levels of iron-deficient and iron-sufficient carriers and examined the correlation between low HbA2 levels and ferritin level. Because ferritin is an acute-phase reactant, similar evaluations were made by using transferrin saturation as the criterion for iron deficiency.

Results: The median HbA2 value of iron-deficient carrier children was 4.1% and within the diagnostic range (≥3.5%) in the majority of children. Median HbA2 levels in iron-deficient carriers differed from levels in iron-sufficient carriers (4.1% vs 4.9%, P < .007). No correlation was present between low HbA2 levels and ferritin levels (0.226). Furthermore, among children without iron deficiency, there were individuals with low HbA2 levels (26.9%). Similar results were obtained when transferrin saturation was used.

Conclusions: Hemoglobin A2 can be used as a screening test in children with β-thalassemia trait, despite accompanying iron deficiency. Low HbA2 levels in these children may be the result of underlying thalassemia mutation, not the result of accompanying iron deficiency. Therefore, in suspected cases of β-thalassemia trait, evaluation should continue, regardless of iron status or treatment.