HbA2

Hemoglobin A2 (HbA2) is one of the normal hemoglobin types found in adults, alongside HbA (α2β2, ~96-98%) and HbF (α2γ2, <1%). It is produced in small amounts throughout life and increases slightly with age. Quantification of HbA2 via hemoglobin electrophoresis or HPLC is a critical diagnostic tool in the workup of microcytic anemia.

In beta-thalassemia trait (heterozygous beta-thalassemia), there is a compensatory increase in HbA2 (typically >3.5%, often 4-6%) and sometimes mild elevation in HbF, due to decreased beta-globin chain synthesis allowing increased relative production of delta chains. This elevated HbA2 helps distinguish beta-thalassemia trait from iron deficiency anemia, both of which present with microcytic, hypochromic anemia but require very different management (iron supplementation vs. genetic counseling, avoiding unnecessary iron therapy).

Conversely, HbA2 levels may be normal or decreased in iron deficiency anemia, alpha-thalassemia trait, and delta-beta thalassemia (where delta chain production is also impaired). In beta-thalassemia major, HbA2 may be elevated or normal, but the clinical picture is dominated by severe anemia and HbF elevation.

Key clinical pearl: Always check HbA2 and HbF levels when microcytic anemia doesn't respond to iron therapy or when ethnic background (Mediterranean, African, Southeast Asian) suggests possible thalassemia. Iron deficiency can falsely lower HbA2, so iron studies should be checked concurrently or iron deficiency corrected before interpreting HbA2 levels definitively.