This is a young patient who has been transfusion dependent. His recent CBC shows moderate anemia with a significant microcytosis. The differential diagnosis for microcytic anemia is lengthy, including abnormal iron metabolism (iron deficiency, anemia of chronic disease, sideroblastic anemia, lead poisoning, defects of heme or porphoryin synthesis), thalassemia, and some hemoglobinopathies (hemoglobin C or E, but not S).

Keeping this differential in mind, the peripheral smear shows marked microcytosis (compared to the resting lymphocyte) and anisocytosis. Also conspicuous are multiple target cells.

Hemoglobin electrophoresis and HPLC confirm the diagnosis of thalassemia. There is a markedly decreased to absent production of hemoglobin A. The amount of hemoglobin A2 and F are noticeably increased. This is most compatible with beta-thalassemia major. Hemoglobin E can migrate with A2 in both hemoglobin electrophoresis on cellulose acetate and HPLC, but given the severity of the anemia, thalassemia is more likely. Hemoglobin E, even in the homozygous state, rarely causes serious anemia. Isoelectric focusing can be used to separate hemoglobin E from A2.