title: Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders.
abstract: Non-transferrin-bound iron and its labile (redox active) plasma iron component are thought to be potentially toxic forms of iron originally identified in the serum of patients with iron overload. We compared ten worldwide leading assays (6 for non-transferrin-bound iron and 4 for labile plasma iron) as part of an international inter-laboratory study. Serum samples from 60 patients with four different iron-overload disorders in various treatment phases were coded and sent in duplicate for analysis to five different laboratories worldwide. Some laboratories provided multiple assays. Overall, highest assay levels were observed for patients with untreated hereditary hemochromatosis and β-thalassemia intermedia, patients with transfusion-dependent myelodysplastic syndromes and patients with transfusion-dependent and chelated β-thalassemia major. Absolute levels differed considerably between assays and were lower for labile plasma iron than for non-transferrin-bound iron. Four assays also reported negative values. Assays were reproducible with high between-sample and low within-sample variation. Assays correlated and correlations were highest within the group of non-transferrin-bound iron assays and within that of labile plasma iron assays. Increased transferrin saturation, but not ferritin, was a good indicator of the presence of forms of circulating non-transferrin-bound iron. The possibility of using non-transferrin-bound iron and labile plasma iron measures as clinical indicators of overt iron overload and/or of treatment efficacy would largely depend on the rigorous validation and standardization of assays.
authors.affiliation: Departments of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Louise
authors.initials: L
authors.lastname: de Swart
authors.affiliation: Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jan C M
authors.initials: JC
authors.lastname: Hendriks
authors.affiliation: Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Lisa N
authors.initials: LN
authors.lastname: van der Vorm
authors.affiliation: Department of Biochemical Chemistry, Hebrew University of Jerusalem, Israel.
authors.forename: Z Ioav
authors.initials: ZI
authors.lastname: Cabantchik
authors.affiliation: Department of Haematology, University College London, UK.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Evans
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Eldad A
authors.initials: EA
authors.lastname: Hod
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Brittenham
authors.affiliation: Aferrix Ltd., Tel-Aviv, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Furman
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Wojczyk
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Mirian C H
authors.initials: MC
authors.lastname: Janssen
authors.affiliation: Department of Haematology, University College London, UK.
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.affiliation: Department of Hematology, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: Vera E J M
authors.initials: VE
authors.lastname: Mattijssen
authors.affiliation: Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Biemond
authors.affiliation: Departments of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marius A
authors.initials: MA
authors.lastname: MacKenzie
authors.affiliation: Department of Biomedical Science and Biotechnology, Regional Microcythemia Hospital, University of Cagliari, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Origa
authors.affiliation: Department of Biomedical Science and Biotechnology, Regional Microcythemia Hospital, University of Cagliari, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
authors.affiliation: Institute of Pharmaceutical Science, King's College London, UK.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hider
authors.affiliation: Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands dorine.swinkels@radboudumc.nl.
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
mesh_terms: D000328:Adult; D000368:Aged; D001803:Blood Transfusion; D005260:Female; D006432:Hemochromatosis / Q000097:blood*; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000628:therapy; D014168:Transferrin / Q000378:metabolism*; D017086:beta-Thalassemia / Q000097:blood* / Q000628:therapy
chemical_list: D014168:Transferrin; D007501:Iron