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Clinical thresholds for diagnosing iron deficiency: comparison of functional assessment of serum ferritin to population based centiles.
Sci Rep. 2020 10 26; 10(1):18233.SR

Abstract

Low serum ferritin is diagnostic of iron deficiency, yet its published lower cut-off values are highly variable, particularly for pediatric populations. Lower cut-off values are commonly reported as 2.5th percentiles, and is based on the variation of ferritin values in the population. Our objective was to determine whether a functional approach based on iron deficient erythropoiesis could provide a better alternative. Utilizing 64,443 ferritin test results from pediatric electronic health records, we conducted various statistical techniques to derive 2.5th percentiles, and also derived functional reference limits through the association between ferritin and erythrocyte parameters: hemoglobin, mean corpuscular volume, mean cell hemoglobin concentration, and red cell distribution width. We find that lower limits of reference intervals derived as centiles are too low for clinical interpretation. Functional limits indicate iron deficiency anemia starts to occur when ferritin levels reach 10 µg/L, and are largely similar between genders and age groups. In comparison, centiles (2.5%) presented with lower limits overall, with varying levels depending on age and gender. Functionally-derived limits better reflects the underlying physiology of a patient, and may provide a basis for deriving a threshold related to treatment of iron deficiency and any other biomarker with functional outcomes.

Authors+Show Affiliations

Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 6, 75 Talavera Road, Ryde, NSW, 2109, Australia. gorkem.sezgin@mq.edu.au.Department of Pediatrics, The University of Melbourne, Parkville, VIC, Australia. Hematology Research, Murdoch Children's Research Institute, Parkville, VIC, Australia. Department of Hematology, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.Department of Laboratory Medicine, National University Hospital, Kent Ridge, Singapore.Department of Pediatrics, The University of Melbourne, Parkville, VIC, Australia. Hematology Research, Murdoch Children's Research Institute, Parkville, VIC, Australia.Department of Pediatrics, The University of Melbourne, Parkville, VIC, Australia. Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, VIC, Australia.Outcome Health, East Burwood, VIC, Australia.Outcome Health, East Burwood, VIC, Australia.Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 6, 75 Talavera Road, Ryde, NSW, 2109, Australia.Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 6, 75 Talavera Road, Ryde, NSW, 2109, Australia.Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 6, 75 Talavera Road, Ryde, NSW, 2109, Australia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33106588

Citation

Sezgin, Gorkem, et al. "Clinical Thresholds for Diagnosing Iron Deficiency: Comparison of Functional Assessment of Serum Ferritin to Population Based Centiles." Scientific Reports, vol. 10, no. 1, 2020, p. 18233.
Sezgin G, Monagle P, Loh TP, et al. Clinical thresholds for diagnosing iron deficiency: comparison of functional assessment of serum ferritin to population based centiles. Sci Rep. 2020;10(1):18233.
Sezgin, G., Monagle, P., Loh, T. P., Ignjatovic, V., Hoq, M., Pearce, C., McLeod, A., Westbrook, J., Li, L., & Georgiou, A. (2020). Clinical thresholds for diagnosing iron deficiency: comparison of functional assessment of serum ferritin to population based centiles. Scientific Reports, 10(1), 18233. https://doi.org/10.1038/s41598-020-75435-5
Sezgin G, et al. Clinical Thresholds for Diagnosing Iron Deficiency: Comparison of Functional Assessment of Serum Ferritin to Population Based Centiles. Sci Rep. 2020 10 26;10(1):18233. PubMed PMID: 33106588.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical thresholds for diagnosing iron deficiency: comparison of functional assessment of serum ferritin to population based centiles. AU - Sezgin,Gorkem, AU - Monagle,Paul, AU - Loh,Tze Ping, AU - Ignjatovic,Vera, AU - Hoq,Monsurul, AU - Pearce,Christopher, AU - McLeod,Adam, AU - Westbrook,Johanna, AU - Li,Ling, AU - Georgiou,Andrew, Y1 - 2020/10/26/ PY - 2020/09/02/received PY - 2020/10/15/accepted PY - 2020/10/27/entrez PY - 2020/10/28/pubmed PY - 2020/10/28/medline SP - 18233 EP - 18233 JF - Scientific reports JO - Sci Rep VL - 10 IS - 1 N2 - Low serum ferritin is diagnostic of iron deficiency, yet its published lower cut-off values are highly variable, particularly for pediatric populations. Lower cut-off values are commonly reported as 2.5th percentiles, and is based on the variation of ferritin values in the population. Our objective was to determine whether a functional approach based on iron deficient erythropoiesis could provide a better alternative. Utilizing 64,443 ferritin test results from pediatric electronic health records, we conducted various statistical techniques to derive 2.5th percentiles, and also derived functional reference limits through the association between ferritin and erythrocyte parameters: hemoglobin, mean corpuscular volume, mean cell hemoglobin concentration, and red cell distribution width. We find that lower limits of reference intervals derived as centiles are too low for clinical interpretation. Functional limits indicate iron deficiency anemia starts to occur when ferritin levels reach 10 µg/L, and are largely similar between genders and age groups. In comparison, centiles (2.5%) presented with lower limits overall, with varying levels depending on age and gender. Functionally-derived limits better reflects the underlying physiology of a patient, and may provide a basis for deriving a threshold related to treatment of iron deficiency and any other biomarker with functional outcomes. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/33106588/Clinical_thresholds_for_diagnosing_iron_deficiency:_comparison_of_functional_assessment_of_serum_ferritin_to_population_based_centiles L2 - https://doi.org/10.1038/s41598-020-75435-5 DB - PRIME DP - Unbound Medicine ER -
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