title: Results of an international round robin for the quantification of serum non-transferrin-bound iron: Need for defining standardization and a clinically relevant isoform.
abstract: Non-transferrin-bound iron (NTBI) appears in the circulation of patients with iron overload. Various methods to measure NTBI were comparatively assessed as part of an international interlaboratory study. Six laboratories participated in the study, using methods based on iron mobilization and detection with iron chelators or on reactivity with bleomycin. Serum samples of 12 patients with hereditary (n=11) and secondary (n=1) hemochromatosis were measured during a 3-day analysis using 4 determinations per sample per day, making a total of 144 measurements per laboratory. Bland-Altman plots for repeated measurements are presented. The methods differed widely in mean serum NTBI level (range 0.12-4.32mumol/L), between-sample variation (SD range 0.20-2.13mumol/L and CV range 49.3-391.3%), and within-sample variation (SD range 0.02-0.45mumol/L and CV range 4.4-193.2%). The results obtained with methods based on chelators correlated significantly (R(2) range 0.86-0.99). On the other hand, NTBI values obtained by the various methods related differently from those of serum transferrin saturation (TS) when expressed in terms of both regression coefficients and NTBI levels at TS of 50%. Recent studies underscore the clinical relevance of NTBI in the management of iron-overloaded patients. However, before measurement of NTBI can be introduced into clinical practice, there is a need for more reproducible protocols as well as information on which method best represents the pathophysiological phenomenon and is most pertinent for diagnostic and therapeutic purposes.
authors.affiliation: Department of Clinical Chemistry, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.
authors.forename: Esther M G
authors.initials: EM
authors.lastname: Jacobs
authors.forename: Jan C M
authors.initials: JC
authors.lastname: Hendriks
authors.forename: Berry L J H
authors.initials: BL
authors.lastname: van Tits
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Evans
authors.forename: William
authors.initials: W
authors.lastname: Breuer
authors.forename: Ding Yong
authors.initials: DY
authors.lastname: Liu
authors.forename: Eugene H J M
authors.initials: EH
authors.lastname: Jansen
authors.forename: Katri
authors.initials: K
authors.lastname: Jauhiainen
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sturm
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.forename: Barbara
authors.initials: B
authors.lastname: Scheiber-Mojdehkar
authors.forename: Leni
authors.initials: L
authors.lastname: von Bonsdorff
authors.forename: Z Ioav
authors.initials: ZI
authors.lastname: Cabantchik
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hider
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
mesh_terms: D001761:Bleomycin / Q000737:chemistry; D001774:Blood Chemical Analysis / Q000592:standards; D002614:Chelating Agents / Q000737:chemistry; D006432:Hemochromatosis / Q000175:diagnosis*; D006801:Humans; D007501:Iron / Q000097:blood*; D020033:Protein Isoforms / Q000097:blood; D014168:Transferrin / Q000032:analysis
chemical_list: D002614:Chelating Agents; D020033:Protein Isoforms; D014168:Transferrin; D001761:Bleomycin; D007501:Iron