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Cited by 328Iron Metabolism and DisordersErythropoietin and Anemia TreatmentHemoglobinopathies and Related Disorders

Guidelines on the diagnosis and treatment of iron deficiency across indications: A systematic review

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Peyrin-Biroulet, Laurent, Williet, Nicolas, Cacoub, Patrice·2015·The American Journal of Clinical Nutrition
DOI 10.3945/ajcn.114.103366
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Abstract

Background Guidelines on the diagnosis and treatment of iron deficiency (ID) vary widely across indications.Objective We reviewed all available guidelines on the management of ID worldwide.Design A literature search was conducted in PubMed, Cochrane, and EMBASE and in main professional association websites, limited to documents published between 1 January 2004 and 30 June 2014.Results Of 127 guidelines identified, 29 were selected, involving 29 professional associations and issued from the United States (n = 8), Europe (n = 6), Britain (n = 4), Canada (n = 3), international organizations (n = 2), France (n = 2), Poland (n = 1), Australia (n = 1), Mexico (n = 1), and Japan (n = 1). A total of 22 and 27 guidelines provided recommendations on diagnosis and treatment of ID, respectively. To define ID, all guidelines recommended a concentration for serum ferritin. One-half of them (10 of 22) proposed transferrin saturation (TSAT) as an alternative or complementary diagnostic test. To treat ID, most of the guidelines (18 of 27) recommended preferentially the oral route if possible, particularly in children and in women in the pre- or postpregnancy period. Iron supplementation should be administered intravenously according to 13 of 27 guidelines, particularly in patients with chronic kidney disease (CKD) (n = 7) and chemotherapy-induced anemia (n = 5). Treatment targets for ID included an increase in hemoglobin concentrations to 10-12 g/dL or normalization (n = 8) and serum ferritin >100 μg/L (n = 7) or 200 μg/L (n = 4). For the latter, in some situations, such as CKD, ferritin concentrations should not exceed 500 μg/L (n = 5) or 800 μg/L (n = 5). Only 9 guidelines recommended TSAT as a target, proposing various thresholds ranging from 20% to 50%.Conclusions It appears that for the diagnosis of ID, a cutoff of 100 μg/L for serum ferritin concentration should be considered in most conditions and 20% for TSAT, except in particular situations, including young healthy women with heavy menstrual flow. New indications of intravenous iron supplementation are emerging.

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  • The authors concluded that an SF threshold of <45 ng/mL was believed to be the most accurate for diagnosing ID.

    “The authors concluded that an SF threshold of <45 ng/mL was believed to be the most accurate for diagnosing ID [37].”

    From Defining Global Thresholds for Serum Ferritin: A Challenging Mission in Establishing the Iron Deficiency Diagnosis in This Era of Striving for Health Equity (2025) · cites this paper as [37]

    The Discussion (page not provided) concludes that a serum ferritin cutoff of 100 ng/mL should be considered to define iron deficiency in most conditions. The Ferritin concentration to define ID section reports that three guidelines proposed a 45–50 ng/mL threshold; it does not present that threshold as the authors’ conclusion or as the most accurate. (LLM, conf=0.90)

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  • The authors suggested that functional iron deficiency is defined by SF >100 ng/mL and TSAT <20%, whereas absolute ID is defined by SF <100 ng/dL and TSAT <20%.

    “The authors suggested the FID which is defined by SF >100 ng/mL and TSAT <20%, whereas absolute ID is defined by SF <100 ng/dL and TSAT <20%.”

    From Defining Global Thresholds for Serum Ferritin: A Challenging Mission in Establishing the Iron Deficiency Diagnosis in This Era of Striving for Health Equity (2025) · cites this paper as [37]

    The Discussion defines functional iron deficiency as ferritin above 100 and TSAT below 20%, and absolute iron deficiency as ferritin below 100 and TSAT below 20%. But it gives the same ferritin unit for both definitions; the citing sentence uses ng/mL for one and ng/dL for the other, which are not equivalent. (LLM, conf=0.88)

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  • In a systematic review of 55 studies, an SF threshold of <45 ng/mL had a sensitivity and specificity for ID of 85% and 92%, respectively, whereas an SF of <15 ng/mL had a sensitivity and specificity of only 59% and 99%, respectively.

    “In a systematic review of 55 studies, an SF threshold of <45 ng/mL had a sensitivity and specificity for ID of 85% and 92%, respectively. Conversely, an SF of <15 ng/mL had a sensitivity and specificity of only 59% and 99%, respectively.”

    From Defining Global Thresholds for Serum Ferritin: A Challenging Mission in Establishing the Iron Deficiency Diagnosis in This Era of Striving for Health Equity (2025) · cites this paper as [37]

    The ‘Ferritin concentration to define ID’ section reports that guidelines proposed thresholds of 12–15 and 45–50 ng/mL. It does not report the claimed sensitivity and specificity values or a review of 55 studies; the ‘Diagnosis of ID’ section describes 22 guidelines instead. No page number is available in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Laurent et al. analyzed 29 guidelines published over the last decade and proposed an SF concentration cutoff of 100 ng/mL should be considered in current practices and further clinical trials to define ID in most conditions.

    “Laurent et al. [37] analyzed 29 guidelines published over the last decade. They proposed an SF concentration cutoff of 100 ng/mL should be considered in current practices and further clinical trials to define an ID in most conditions.”

    From Defining Global Thresholds for Serum Ferritin: A Challenging Mission in Establishing the Iron Deficiency Diagnosis in This Era of Striving for Health Equity (2025) · cites this paper as [37]

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Research works printed but not linked: 1

  1. [46]46. II. Clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease in adults. Am J Kidney Dis 2006; 47:S16-85.

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Authors
Peyrin-Biroulet, L., Williet, N., & Cacoub, P.
Affiliations
  • Inserm (FR)
  • Centre National de la Recherche Scientifique (FR)
ORCID
Venue
The American Journal of Clinical Nutrition
Publisher
Elsevier BV
Published
2015-12
Volume
102
Issue
6
Pages
1585-1594
ISSN
0002-9165 (ISSN-L)
DOI
10.3945/ajcn.114.103366
OpenAlex
W2179606064
Cited by
328
References
58
Citations by year
2026: 13 · 2025: 36 · 2024: 41 · 2023: 38 · 2022: 36 · 2021: 29 · 2020: 40 · 2019: 16 · 2018: 40 · 2017: 28 · 2016: 10 · 2015: 1
FWCI
3.94
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal of Clinical Nutrition (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Society of Clinical Oncology
  • Kræftens Bekæmpelse
  • National Institute for Health and Care Excellence
  • National Comprehensive Cancer Network
  • European Crohn's and Colitis Organisation
  • European Society of Cardiology
  • Gastroenterological Society of Australia
  • European Organisation for Research and Treatment of Cancer
  • European Society for Medical Oncology
  • European Society of Anaesthesiology
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
Keywords
iron deficiency, iron deficiency diagnosis, iron deficiency treatment, serum ferritin, transferrin saturation, iron supplementation, intravenous iron, oral iron, chronic kidney disease, chemotherapy-induced anemia, hemoglobin target, guideline recommendations, iron deficiency anemia, women of reproductive age, heavy menstrual flow
MeSH terms
Algorithms, Ferric Compounds, Ferritins, Hematinics, Humans, Societies, Medical, Global Health, Biomarkers, Down-Regulation, Practice Guidelines as Topic, Anemia, Iron-Deficiency, Iron Overload, Iron, Dietary, Dietary Supplements, Renal Insufficiency, Chronic, Administration, Intravenous

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