Thalassemias are a heterogeneous group of inherited disorders resulting form defects in hemoglobin synthesis (hemoglobinopathies). Production of either α- or β-chains, the protein constituent of hemoglobin, is impaired, leading to decreased hemoglobin formation. As a result, erythropoietic cells in the bone marrow die prematurely (ineffective erythropoiesis). In addition, "partnerless" chains aggregate, leading to premature destruction of erythrocytes in the spleen (hemolysis). Thalassemias occur frequently in people who inhabit the Mediterranean, the Near East, the Indian subcontinent and southeast Asia. Hemoglobin electrophoresis, high performance liquid chromatography (HPLC) and molecular methods are used to establish the diagnosis.
β-thalassemias can be divided into a severe form (thalassemia major, homozygous form) and a mild form (thalassemia minor, heterozygous form). The latter is usually asymptomatic, whereas the former is associated with a severe anemia, which leads to intrauterine death (hydrops fetalis) or requires frequent transfusions, resulting in iron overload that may limits life. The clinical picture of a homozygous but less severe form of β-thalassemia is called thalassemia intermedia.
In α-thalassemias, the deletion of all 4 α-globin genes lead to hydrops fetalis, the deletion of 3 α-globin genes leads to HbH disease, and the deletion of only 1 α-globin gene leads to α-thalassemia trait. The latter disease is very mild.
The anemia in thalassemia is hypochromic and microcytic. For this reason, it is often incorrectly diagnosed as an iron deficiency anemia. However, in contrast to iron deficiency anemia, the ferritin level is normal or high in thalassemia and the erythrocyte count is increased or minimally decreased. The MCV is disproportionately reduced in comparison to the hemoglobin concentration. RDW is mostly normal. Poikilocytosis, polychromasia and target cells are also typically seen in the blood film. In severe cases, normoblasts (nucleated red cells) can be seen as well.
Red cell inclusions can be demonstrated in HbH disease by staining with brilliant cresyl blue.