The major cause of iron overload in persons with severe hemoglobinopathies is repeated transfusion of erythrocytes. Because body mechanisms to excrete iron are extremely limited, the short-term benefits of chronic transfusion are followed by the eventual development of iron overload and associated disorders. In some patients, especially those who also have thalassemia alleles (Chapter 21), dietary iron absorption is increased due to suppression of hepcidin production as a consequence of increased erythropoiesis or to mutations in iron regulatory genes. Prevention and treatment of iron overload in this heterogeneous group of patients has emerged as another clinical challenge in their management.

History

The advent of safe transfusion practices and the availability of erythrocytes for transfusion in some areas of the world during the twentieth century was associated with the development of iron overload in patients with several types of chronic anemia, including hemoglobinopathies. For more than five decades, the episodic use of erythrocyte transfusion to prevent or alleviate complications of hemolysis and intravascular sickling in African-Americans with sickle cell disease has increased. For more than three decades, systematic chronic erythrocyte transfusion has been used to decrease the incidence of recurrent stroke and premature death in sickle cell disease, especially in children. Hemoglobinopathy E, sometimes co-inherited with beta-thalassemia alleles, is very common in some Asian countries. Many patients require periodic erythrocyte transfusions to alleviate chronic severe anemia. Worldwide, chronic erythrocyte transfusion and improvement in other treatment modalities increase quality and length of life in some patients with severe hemoglobinopathy syndromes.