title: Management of iron overload in hemoglobinopathies: what is the appropriate target iron level?
abstract: Patients with thalassemia become iron overloaded from increased absorption of iron, ineffective erythropoiesis, and chronic transfusion. Before effective iron chelation became available, thalassemia major patients died of iron-related cardiac failure in the second decade of life. Initial treatment goals for chelation therapy were aimed at levels of ferritin and liver iron concentrations associated with prevention of adverse cardiac outcomes and avoidance of chelator toxicity. Cardiac deaths were greatly reduced and survival was much longer. Epidemiological data from the general population draw clear associations between increased transferrin saturation (and, by inference, labile iron) and early death, diabetes, and malignant transformation. The rate of cancers now seems to be significantly higher in thalassemia than in the general population. Reduction in iron can reverse many of these complications and reduce the risk of malignancy. As toxicity can result from prolonged exposure to even low levels of excess iron, and survival in thalassemia patients is now many decades, it would seem prudent to refocus attention on prevention of long-term complications of iron overload and to maintain labile iron and total body iron levels within a normal range, if expertise and resources are available to avoid complications of overtreatment.
authors.affiliation: Section of Hematology, Children's Center for Cancer, Blood Diseases and Bone Marrow Transplantation.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Coates
authors.affiliation: Section of Hematology, Children's Center for Cancer, Blood Diseases and Bone Marrow Transplantation.
authors.forename: Susan
authors.initials: S
authors.lastname: Carson
authors.affiliation: Division of Cardiology, Children's Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, California.
authors.forename: John C
authors.initials: JC
authors.lastname: Wood
authors.affiliation: Section of Hematology, Children's Center for Cancer, Blood Diseases and Bone Marrow Transplantation.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Berdoukas
mesh_terms: D000818:Animals; D015913:Chelation Therapy / Q000379:methods* / Q000639:trends; D019468:Disease Management; D006453:Hemoglobinopathies / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D007501:Iron / Q000097:blood; D019190:Iron Overload / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*
chemical_list: D007501:Iron
keywords: cancer; epidemiology; hemoglobinopathy; iron toxicity; outcomes; thalassemia; transferrin saturation; treatment