title: Iron metabolism and iron chelation in sickle cell disease.
abstract: This review highlights recent advances in iron metabolism that are relevant to sickle cell disease (SCD). SCD is a common hemoglobinopathy that results in chronic inflammation. Improved understanding of how iron metabolism is controlled by proteins such as hepcidin, ferroportin, hypoxia-inducible factor 1, and growth differentiation factor 15 have revealed how they are involved in the organ toxicity of SCD. SCD patients have lower levels of non-transferrin-bound iron (NTBI) relative to other hemoglobinopathies, such as thalassemia. Care for SCD now commonly uses transfusion that results in iron overload and necessitates the need for chelation. New oral chelation therapy using deferasirox (Exjade/ICL670) appears to be safe and may even lower the amount of toxic free NTBI and enhance patient compliance. Finally, we suggest that iron metabolism and trafficking is different in SCD compared to other hemoglobinopathies. The high levels of inflammatory cytokines in SCD may enhance macrophage/reticuloendothelial cell iron and/or renal cell iron retention. This makes the tissues that retain iron different in SCD, and thus the organs that fail in SCD are different from those of other hemoglobinopathies, such as the cardiomyopathy or endocrinopathies of thalassemia.
authors.affiliation: Children's Hospital & Research Center Oakland, Oakland, Calif., USA.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Walter
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
mesh_terms: D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000627:therapeutic use*
chemical_list: D007502:Iron Chelating Agents; D007501:Iron