Excretion and Distribution of Iron During Chronic Deferoxamine Therapy

Abstract

Abstract In order to evaluate the consequences of chronic chelation therapy on iron overload, the cumulative excretion and tissue distribution of iron were analyzed in a child given deferoxamine (DFO) for transfusion hemosiderosis. During 5 yr of treatment, DFO induced a mean urinary loss of 13.0 mg iron per 24 hr per 500 mg injected. Of the 32 grams of iron administered as transfused red cells during the treatment period 30% was recovered in the urine. Mapping of the tissue distribution of iron was facilitated by splenectomy after 41 mo of chelation therapy. Despite an abundance of iron in Kupffer cells and bone marrow reticulum cells, the spleen was depleted of iron. The heterogeneous distribution of reticuloendothelial iron suggests that the spleen contains a reservoir of metabolically active, chelatable iron, whereas those parts of the reticuloendothelial system less active in heme catabolism store iron in a metabolically dormant, nonchelatable pool. The capacity of DFO to chelate spleen iron in the face of severe erythroid hypoplasia suggests that transferrin-prompted flow of iron across cell membranes is not necessary for chelate mobilization.