An update on iron chelation therapy.

Abstract

Iron overload is a common clinical problem, arising from disorders of increased iron absorption such as hereditary haemochromatosis or thalassaemia intermedia syndromes or as a consequence of chronic blood transfusions for various blood disorders. Regular red blood cell (RBC) transfusions are the principal supportive therapy for many rare anaemias involving a decrease in RBC production, an increase in cell destruction, or chronic blood loss1. Anaemias such as beta-thalassaemia and sickle cell disease are examples of chronic diseases that require long-term transfusion therapy to improve life expectancy. Although transfusion requirements may vary according to the diagnosis, chronic blood transfusion therapy inevitably leads to secondary iron overload that can cause significant damage to many organs, such as the liver and heart, and to the endocrine system2,3. Iron overload is associated with the production of free radicals that can damage tissues, resulting in cardiac toxicity, endocrine dysfunction, and liver toxicity. The effects of iron overload are visible after damage has been done, when patients already have liver dysfunction, cirrhosis, cardiomyopathy or diabetes1,4. Iron is an essential element within the body and its quantity is tightly regulated physiologically; however, the body has no mechanism to excrete excess iron and it deposits iron into end organs leading to severe dysfunction. Each unit of RBC transfused contains 180 to 200 mg of iron. Chronic packed RBC transfusion therapy increases liver iron by approximately 1 mg/mL (by dry weight) for every 15 mL/kg delivered5. Labile plasma iron (LPI) is a toxic and chelatable form of iron that is produced continually during conditions of iron overload, and has been linked to the development of co-morbidities6. It is very important to remove excess iron and suppress LPI to avoid the serious clinical sequelae associated with iron overload. In this specific context phlebotomy cannot be used because patients are usually anaemic and other means must be used to mobilise the excess iron. The gold standard is iron chelation therapy.