Thalassemia

THALASSEMIA

The thalassemias are a group of hereditary disorders associated with defective hemoglobin-chain synthesis. These anemias occur worldwide, but the highest prevalence is found in people of Mediterranean, African, and Southeast Asian ancestry (Hoffman et al., 2000). Thalassemias are characterized by hypochromia (an abnormal decrease in the hemoglobin content of RBCs), extreme microcytosis (smaller-than-normal RBCs), destruction of bloodelements (hemolysis), and variable degrees of anemia.

In thalassemia, the production of one or more globulin chains within the hemoglobin molecule is reduced. When this occurs, the imbalance in the configuration of the hemoglobin causes it to precipitate in the erythroid precursors or the RBCs themselves. This increases the rigidity of the RBCs and thus the premature destruction of these cells.

The thalassemias are classified into two major groups accord-ing to the globin chain diminished: alpha and beta. The alpha-thalassemias occur mainly in people from Asia and the Middle East; the beta-thalassemias are most prevalent in Mediterranean populations but also occur in people from the Middle East or Asia. The alpha-thalassemias are milder than the beta forms and often occur without symptoms. The RBCs are extremely micro-cytic, but the anemia, if present, is mild.

The severity of beta-thalassemia varies depending on the ex-tent to which the hemoglobin chains are affected. Patients with mild forms have a microcytosis and mild anemia. If left un-treated, severe beta-thalassemia (thalassemia major, or Cooley’s anemia) can be fatal within the first few years of life. If it is treated with regular transfusion of RBCs, patients may survive into their 20s and 30s. Patient teaching during the reproductive years should include pre-conception counseling about the risk of con-genital thalassemia major.

Thalassemia Major

Thalassemia major (Cooley’s anemia) is characterized by severe anemia, marked hemolysis, and ineffective erythropoiesis (produc-tion of RBCs). With early regular transfusion therapy, growth and development through childhood are facilitated. Organ dysfunction due to iron overload results from the excessive amounts of iron ob-tained through the RBC transfusions. Regular chelation therapy (eg, via subcutaneous deferoxamine) has reduced the complications of iron overload and prolonged the life of these patients. This dis-ease is potentially curable by BMT if the procedure can be per-formed before damage to the liver occurs (ie, during childhood).