Results of an international round robin for the quantification of serum non-transferrin-bound iron: Need for defining standardization and a clinically relevant isoform

Jacobs, Esther; Hendriks, Jan C.M.; Tits, Berry L.J.H. van; Evans, Patricia; Breuer, William; Liu, Ding Yong; Jansen, Eugène; Jauhiainen, Katri; Sturm, Brigitte; Porter, John B.; Scheiber-Mojdehkar, Barbara; Bonsdorff, Leni von; Cabantchik, Z. Ioav; Hider, Robert C.; Swinkels, Dorine W.

doi:10.1016/j.ab.2005.03.008

Cited by 94 publications

(66 citation statements)

References 25 publications

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“…It has been observed that with the increase in the concentration of NTA there is also a parallel increase in the concentration of NTBI estimated [63]. In the method described by Gosriwatana et al [19,62,64,65] 80 mM NTA was suggested as compared to the other methods where lower concentrations of NTA was used. However Kolb et al [63] suggested that 4 mM NTA is the best suitable concentration for chelation of NTBI.…”

Section: Chelation Of Ntbi With Chelator Followed By Its Separation Amentioning

confidence: 99%

“…However Kolb et al [63] suggested that 4 mM NTA is the best suitable concentration for chelation of NTBI. This chelated fraction of iron is separated from plasma protein with ultra filter of cut off of 30,000 [64]. This step is operated to minimize the donation of chelated iron to the free sites of traditional iron binding protein like apotransferrin (aTf).…”

Section: Chelation Of Ntbi With Chelator Followed By Its Separation Amentioning

confidence: 99%

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Non Transferrin Bound Iron: Nature, Manifestations and Analytical Approaches for Estimation

Patel

Ramavataram

2012

Ind J Clin Biochem

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Section: Chelation Of Ntbi With Chelator Followed By Its Separation Amentioning

confidence: 99%

Section: Chelation Of Ntbi With Chelator Followed By Its Separation Amentioning

confidence: 99%

Non Transferrin Bound Iron: Nature, Manifestations and Analytical Approaches for Estimation

Patel

Ramavataram

2012

Ind J Clin Biochem

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“…NTBI appears in the blood when transferrin is highly saturated so its presence can be predicted by TSAT values [8]. NTBI is toxic to the liver, heart, and other endocrine tissues and increased blood levels may indicate developing organ toxicity in iron-overloaded patients.…”

Section: Tsatmentioning

confidence: 99%

Diagnosis and management of transfusion iron overload: The role of imaging

Wood

2007

Am. J. Hematol.

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The characterization of iron stores is important to prevent and treat iron overload. Serum markers such as ferritin, serum iron, iron binding capacity, transferrin saturation, and nontransferrin‐bound iron can be used to follow trends in iron status; however, variability in these markers limits predictive power for any given individual. Liver iron represents the best single marker of total iron balance. Measures of liver iron include biopsy, superconducting quantum interference device, computer tomography, and magnetic resonance imaging (MRI). MRI is the most accurate and widely available noninvasive tool to assess liver iron. The main advantages of MRI include a low‐rate of variability between measurements and the ability to assess iron loading in endocrine tissues, the heart and the liver. This manuscript describes the principles, validation, and clinical utility of MRI for tissue iron estimation. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.

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“…In view of the above, it is not surprising that a gold standard for NTBI determination has not emerged and the values obtained often depend on the assay used [13]. This implies that in practical diagnostic terms using a single NTBI assay method may provide an incomplete picture.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the composition of NTBI might vary with the degree and source of iron overload, treatment of the patient with chelator or phlebotomy and the sample storage conditions which, ideally, should preserve both the TBI and the NTBI components. Due to the chemical complexity and potential clinical importance of NTBI, a number of alternative methods have been developed for its detection [12,13] with the objective of obtaining a better measure of the total content of NTBI in a patient sample. In general, these methods have relied on the principle of using a powerful chelator or high concentrations of mobilizing agents (with or without a filtration step), to maximize NTBI's accessibility to the various iron-detecting reagents [11,[14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Non‐transferrin bound iron in Thalassemia: Differential detection of redox active forms in children and older patients

Breuer¹,

Ghoti

Shattat³

et al. 2011

American J Hematol

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Non-transferrin bound iron (NTBI) is commonly detected in patients with systemic iron overload whose serum iron-binding capacity has been surpassed. It has been perceived as an indicator of iron overload, impending organ damage and a chelation target in poly-transfused thalassemia patients. However, NTBI is a heterogeneous entity comprising various iron complexes, including a significant redox-active and readily chelatable fraction, which we have designated as ''labile plasma iron'' (LPI). We found that LPI levels can be affected by plasma components such as citrate, uric acid, and albumin. However, the inclusion of a mild metal mobilizing agent in the LPI assay (designated here as ''eLPI''), at concentrations that do not affect transferrin-bound iron, largely overcomes such effects and provides a measure of the full NTBI content. We analyzed three distinct groups of poly-transfused, iron overloaded thalassemia patients: non-chelated children (3-13 yrs, Gaza, Palestine), chelated adolescents-young adults (13-28 yrs, Israel), and chelated adults (27-61 yrs, Israel) for LPI and eLPI. The eLPI levels in all three groups were roughly commensurate (r 2 5 0.61-0.75) with deferrioxamine-detectable NTBI, i.e., DCI. In older chelated patients, eLPI levels approximated those of LPI, but in poly-transfused unchelated children eLPI was notably higher than LPI, a difference attributed to plasma properties affected by labile iron due to lack of chelation, possibly reflecting age-dependent attrition of plasma components. We propose that the two formats of NTBI measurement presented here are complementary and used together could provide more comprehensive information on the forms of NTBI in patients and their response to chelation. Am. J. Hematol. 87:55-61, 2012. V

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Results of an international round robin for the quantification of serum non-transferrin-bound iron: Need for defining standardization and a clinically relevant isoform

Cited by 94 publications

References 25 publications

Non Transferrin Bound Iron: Nature, Manifestations and Analytical Approaches for Estimation

Non Transferrin Bound Iron: Nature, Manifestations and Analytical Approaches for Estimation

Diagnosis and management of transfusion iron overload: The role of imaging

Non‐transferrin bound iron in Thalassemia: Differential detection of redox active forms in children and older patients

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