DIFFERENTIAL DIAGNOSIS OF THALASSEMIA
Signs, symptoms, and CBC results are strikingly similar in microcytic hypochromic anemias regardless of the etiology of the anemia, making the clinical diagnosis difficult. Differentiating the various thalassemias is even more difficult because they are all inherited and occur in similar nationalities. Additional laboratory tests are therefore crucial in making the differential diagnosis (Web Table 13.2).
a-Thalassemia vs. b-Thalassemia
The symptomatic thalassemias are usually diagnosed through a combination of clinical examination and hematological evaluation. The changes in erythrocyte morphology are substantial yet similar between the two dominant thalassemic conditions. However, hemoglobin electrophoresis reveals abnormal patterns that are helpful in making the distinction. In the a-thalassemias, all three normal adult hemoglobins, Hb A, A2, and F, are decreased and partially compensated for by Hb H (b4) and Hb Barts (g4). In contrast, the b-thalassemias show a decrease in Hb A with a compensatory increase in Hb F and A2 (Web Table 13.2).
Thalassemia vs. Iron Deficiency Anemia
Thalassemia may be confused with severe iron deficiency anemia because both are characterized by a microcytic hypochromic anemia and increased target cells in the peripheral blood. However, a combination of morphologic assessment, iron studies, hemoglobin electrophoresis patterns, and free erythrocyte protoporphyrin (FEP) levels is generally sufficient to make the distinction. Web Table 13.2 summarizes the laboratory tests used to differentiate thalassemia from iron deficiency anemia. The iron panel and free erythrocyte protoporphyrin will be abnormal in patients with iron deficiency anemia and normal in thalassemia. Hemoglobin electrophoresis will show a normal hemoglobin pattern in iron deficiency anemia and an abnormal pattern in thalassemia. Iron deficiency may, however, co-exist with thalassemia, complicating the diagnosis (Figure 13.14). Successful treatment of the iron deficiency accompanied by persistent microcytosis suggests the presence of thalassemia. Further investigation to help determine the cause of the persistent microcytosis is suggested. Lastly, family studies are helpful in identifying the hereditary nature of the anemia in thalassemia.
b-Thalassemia Major vs. HPFH
b-thalassemia major can also be confused with hereditary persistence of fetal hemoglobin (HPFH), since both produce high levels of Hb F. The acid elution technique of Kleihauer and Betke can be helpful in making the distinction. Hb F in the erythrocytes of patients with b-thalassemia major is distributed in a more heterogeneous fashion, present in some and absent in others, while in HPFH the distribution is more homogeneous (evenly distributed across most erythrocytes) (Web Table 13.2).