Management of iron overload in hemoglobinopathies.

ABSTRACT

Hemoglobinopathies, thalassemia and sickle cell disease are among the most frequent monogenic diseases in the world. Transfusion has improved dramatically their prognosis, but provokes iron overload, which induces multiple organ damages. Iron overload is related to accumulation of iron released from hemolysis and transfused red cell, but also, in thalassemic patients, secondary to ineffective erythropoiesis, which increases intestinal iron absorption via decreased hepcidin production. Transfusion-related cardiac iron overload remains a main cause of death in thalassemia in well-resourced countries, and is responsible for severe hepatic damages in sickle cell disease. Regular monitoring by Magnetic Resonance Imaging (MRI) using myocardial T2* (ms) and Liver Iron Content (LIC) (mg of iron/g dry weight) are now standards of care in chronically transfused patients. Serum ferritin level measurements and record of the total number of transfused erythrocyte concentrates are also helpful tools. Three iron chelators are currently available, deferoxamine, which must be injected subcutaneously or intravenously, and two oral chelators, deferiprone and deferasirox. We will review the main characteristics of these drugs and their indications.