title: Pathophysiology of transfusional iron overload: contrasting patterns in thalassemia major and sickle cell disease.
abstract: The pathophysiological consequences of transfusional iron overload largely reflect the pattern of excess iron distribution and include cardiomyopathy, endocrinopathy, cirrhosis, and hepatocellular carcinoma. Since the introduction of desferrioxamine (DFO) in the late 1970s, these complications have fallen substantially but approximately half of the chelated adult patients with thalassemia major (TM) still show evidence of increased myocardial iron loading by MRI. An understanding of the factors that determine the propensity to extrahepatic iron distribution may be a key to minimizing the pathophysiological consequences of transfusional iron overload. Transfused patients with sickle cell disease (SCD) appear less likely to develop these extrahepatic complications, possibly because plasma nontransferrin-bound iron (NTBI) levels are typically lower than in TM patients at matched levels of iron loading. Other mechanisms that may reduce the extrahepatic iron distribution in SCD include raised plasma hepcidin due to chronic inflammation, lower growth differentiation factor 15 (GDF15) levels because of less ineffective erythropoiesis (IE), and induction of heme oxygenase (HO1) by intravascular hemolysis. Further understanding of these mechanisms may help in designing strategies to decrease extrahepatic iron distribution in TM.
authors.affiliation: Department of Haematology, University College London, London, UK. j.porter@ ucl.ac.uk
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications* / Q000628:therapy; D006801:Humans; D007501:Iron / Q000378:metabolism / Q000633:toxicity; D019190:Iron Overload / Q000150:complications* / Q000188:drug therapy / Q000209:etiology; D014018:Tissue Distribution; D065227:Transfusion Reaction; D017086:beta-Thalassemia / Q000150:complications* / Q000628:therapy
chemical_list: D007501:Iron