Introduction

The efficacy of phlebotomy in the treatment of hemochromatosis is well established and described in detail elsewhere in this volume. Each pint of blood removed represents approximately 200 μg of iron, and there is no other method that could be compared with the efficacy and availability of this mode of intervention. However, phlebotomy requires an intact hemopoietic system and is not suitable for patients with hereditary and other chronic anemias who require blood transfusions for their survival. For these patients, iron chelating therapy is the only available method of protection against the life-threatening consequences of severe transfusional iron overload. Because aggressive iron-chelating treatment can reverse existing iron-induced cardiomyopathy, iron chelation (in addition to phlebotomy) may also be considered in newly diagnosed hemochromatosis patients with cardiomyopathy in whom an immediate threat of fatal complications may not allow sufficient time for the effective removal of iron by phlebotomy alone. The iron-chelating drug deferoxamine (DF) had a major impact on the life expectancy of children with thalassemia. In this chapter the pharmacology of DF will be reviewed, the compartments of body iron available for chelation defined, the mechanism of iron-induced myocardial injury discussed, the impact of long-term DF therapy on life expectancy in transfusion iron overload discussed, and the development of orally effective iron chelators of potential clinical usefulness reviewed.

Deferoxamine pharmacology

The discovery of deferoxamine (DF), the useful iron chelator for the management of transfusion iron overload, was accidental. As described by Keberle, ferrioxamine B was first identified as an antagonist to ferrimycin, a fermentation product with antibiotic properties.