title: Mechanisms of plasma non-transferrin bound iron generation: insights from comparing transfused diamond blackfan anaemia with sickle cell and thalassaemia patients.
abstract: In transfusional iron overload, extra-hepatic iron distribution differs, depending on the underlying condition. Relative mechanisms of plasma non-transferrin bound iron (NTBI) generation may account for these differences. Markers of iron metabolism (plasma NTBI, labile iron, hepcidin, transferrin, monocyte SLC40A1 [ferroportin]), erythropoiesis (growth differentiation factor 15, soluble transferrin receptor) and tissue hypoxia (erythropoietin) were compared in patients with Thalassaemia Major (TM), Sickle Cell Disease and Diamond-Blackfan Anaemia (DBA), with matched transfusion histories. The most striking differences between these conditions were relationships of NTBI to erythropoietic markers, leading us to propose three mechanisms of NTBI generation: iron overload (all), ineffective erythropoiesis (predominantly TM) and low transferrin-iron utilization (DBA).
authors.affiliation: Department of Haematology, University College London, London, UK.
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Walter
authors.forename: Lynne D
authors.initials: LD
authors.lastname: Neumayr
authors.forename: Patricia
authors.initials: P
authors.lastname: Evans
authors.forename: Sukhvinder
authors.initials: S
authors.lastname: Bansal
authors.forename: Maciej
authors.initials: M
authors.lastname: Garbowski
authors.forename: Marcela G
authors.initials: MG
authors.lastname: Weyhmiller
authors.forename: Paul R
authors.initials: PR
authors.lastname: Harmatz
authors.forename: John C
authors.initials: JC
authors.lastname: Wood
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Miller
authors.forename: Colleen
authors.initials: C
authors.lastname: Byrnes
authors.forename: Guenter
authors.initials: G
authors.lastname: Weiss
authors.forename: Markus
authors.initials: M
authors.lastname: Seifert
authors.forename: Regine
authors.initials: R
authors.lastname: Grosse
authors.forename: Dagmar
authors.initials: D
authors.lastname: Grabowski
authors.forename: Angelica
authors.initials: A
authors.lastname: Schmidt
authors.forename: Roland
authors.initials: R
authors.lastname: Fischer
authors.forename: Peter
authors.initials: P
authors.lastname: Nielsen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Niemeyer
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
mesh_terms: D000293:Adolescent; D000328:Adult; D029503:Anemia, Diamond-Blackfan / Q000097:blood* / Q000628:therapy; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000628:therapy; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism; D001803:Blood Transfusion; D004920:Erythropoiesis; D005260:Female; D006801:Humans; D007501:Iron / Q000097:blood*; D019190:Iron Overload / Q000097:blood / Q000209:etiology; D008297:Male; D013789:Thalassemia / Q000097:blood* / Q000628:therapy; D014168:Transferrin
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D014168:Transferrin; D007501:Iron
keywords: NTBI; erythropoiesis; hepcidin; inflammation; iron overload; non-transferrin bound iron