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Use of ferritin concentrations to assess iron status in individuals and populations

Intervention | Last updated: 19 May 2023


Accurate determination of iron status is crucial for diagnostic and screening purposes in the clinical setting and to guide public health interventions to prevent and manage iron deficiency at the population level. In an individual patient, diagnosis of iron deficiency or overload will help guide management, including further investigations and appropriate therapy. At the population level, determination of the magnitude and distribution of iron deficiency can help to prioritize appropriate interventions in settings in which the prevalence is regarded as a severe public health problem, or help to identify populations with hereditary conditions that predispose them to iron overload.

Ferritin is an iron-storage protein present in all cells and can be measured in serum, plasma, liver, red blood cells, and other specimens. Low ferritin concentrations suggest deficient iron stores, whereas elevated ferritin concentrations could suggest iron overload.

Evidence suggests that ferritin concentration is a good marker of iron stores and may be used to monitor and assess the impact of interventions on iron status.

WHO Recommendations


Ferritin concentration is a good marker of iron stores and should be used to diagnose iron deficiency in otherwise apparently healthy individuals.

In individuals with infection or inflammation, a ferritin concentration below 30 µg/L in children and 70 µg/L in adults may be used to indicate iron deficiency (conditional recommendation,5 low certainty of evidence). In populations it is also possible to adjust ferritin values for infection/inflammation by applying correction factors.

A ferritin concentration exceeding 150 µg/L in menstruating women and 200 µg/L in men and non-menstruating women who are otherwise healthy may indicate a risk of iron overload (conditional recommendation, based on previous WHO recommendation). In adult, non-healthy individuals, a ferritin concentration exceeding 500 µg/L may indicate risk of iron overload.

Ferritin concentration should not be used alone to identify risk of iron overload. Patients with elevated ferritin levels should receive clinical and laboratory evaluation to establish the underlying cause.

Ferritin concentration increases in response to iron-related interventions and may be used to monitor and assess the impact of interventions on iron status.

Ferritin may be measured using radiometric, nonradiometric and agglutination assays. One method does not appear to be superior to another and all methods are acceptable if a commutable material traceable to the WHO international reference standard is used to calibrate the assay. Once a method has been selected, that same method should be used for the follow-up of individuals and populations.

Use of the WHO international reference standard of ferritin is recommended for calibration of all commercial kits and in regular laboratory practice, especially when following up individual cases, for population surveys or to measure the impact of public health interventions.

In areas of widespread infection or inflammation, serum ferritin should be assessed with the concurrent measurement of two acute phase response proteins, CRP and AGP.

The increase in ferritin values caused by inflammation should be accounted for in individuals and populations. One method is to raise the cut-off value that defines deficiency, to 30 µg/L or 70 µg/L, depending on the age group. Another method is to exclude individuals with elevated concentrations of CRP or AGP from prevalence calculations based on ferritin. Alternatively, arithmetic or regression correction approaches may be used to adjust ferritin concentrations for inflammation and apply the cut-off points recommended for healthy populations. The adjustment that best suits the country reality should be selected and used as long as those conditions prevail.

 



Evidence


Systematic reviews used to develop the guidelines


Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis

Thurnham DI, McCabe LD, Haldar S, Wieringa FT, Northrop-Clewes CA, McCabe GP. Am J Clin Nutr. 2010;92:546–55.


Performance and comparability of laboratory methods for measuring ferritin concentrations in human serum or plasma: A systematic review and meta-analysis

Garcia-Casal MN, Peña-Rosas JP, Urrechaga E, Escanero JF, Huo J, Martinez RX, Lopez-Perez L. PLoS One. 2018;13(5):e0196576.


Improved micronutrient status and health outcomes in low- and middle-income countries following large-scale fortification: evidence from a systematic review and meta-analysis

Keats E, Neufeld L, Garrett G, Mbuya M, Bhutta Z. Am J Clin Nutr. 2019;109(6):1696–708.


Laboratory diagnosis of iron‐deficiency anemia: an overview

G H Guyatt, A D Oxman, M Ali, A Willan, W McIlroy, C Patterson J Gen Intern Med. 1992;7(2):145-53.


Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Namaste SM, Rohner F, Huang J, Bhushan NL, Flores-Ayala R, Kupka R, Mei Z, Rawat R, Williams AM, Raiten DJ, Northrop-Clewes CA, Suchdev PS. Am J Clin Nutr. 2017;106(Suppl. 1):359S–371S.


Are current serum and plasma ferritin cut-offs for iron deficiency and overload accurate and reflecting iron status? A systematic review

Garcia-Casal MN, Pasricha S-R, Martinez RX, Lopez-Perez L, Peña-Rosas JP. Arch Med Res. 2018;49:405–17.


Serum or plasma ferritin concentration as an index of iron deficiency and overload (protocol)

Garcia‐Casal MN, Pasricha SR, Martinez RX, Lopez‐Perez L, Peña‐Rosas JP. Cochrane Database of Systematic Reviews. 2015; Issue 7. Art. No.: CD011817.


Serum ferritin thresholds for the diagnosis of iron deficiency in pregnancy: a systematic review

Daru J, Allotey J, Peña-Rosas JP, Khan KS. Transfus Med. 2017;27(3):167–74.


The magnitude and distribution across countries of iron deficiency using serum/plasma ferritin

Mei Z, Grummer-Strawn L. Med Res Arch. 2019;7(12).


Response on ferritin concentration from nutrition-specific and nutrition-sensitive interventions in children and women of reproductive age: an overview of reviews (protocol)

Merrill R, Mei Z. (Note: This document includes a summary of the results from a recent systematic review (April 2019). The systematic review has been submitted for publication and is undergoing peer-review.)


Is iron treatment beneficial in, iron-deficient but non-anaemic (IDNA) endurance athletes? A systematic review and meta-analysis

Burden RJ, Morton K, Richards T, Whyte GP, Pedlar CR. Br J Sports Med. 2015;49(21):1389–97.


Cost-effectiveness Learn More Alternate Text


Relevant cost-effectiveness analyses have not yet been identified.