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Cited by 50Iron Metabolism and DisordersErythropoietin and Anemia TreatmentHemoglobinopathies and Related Disorders

The role of reticulocyte hemoglobin content for diagnosis of iron deficiency and iron deficiency anemia, and monitoring of iron therapy: A literature review

Gelaw, Yemataw, Woldu, Berhanu, Melku, Mulugeta·2019·Clinical Laboratory
DOI 10.7754/clin.lab.2019.190315
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Abstract

BACKGROUND: The diagnosis of iron deficiency anemia is still complicated and most of the tests have drawbacks. Bone marrow examination, the gold standard for the diagnosis of iron deficiency and iron deficiency anemia, is a painful, invasive, and costly procedure. Other methods are also used to diagnose iron deficiency and iron deficiency anemia; soluble transferrin receptor, serum iron, serum ferritin, and transferrin saturation are most common biomarkers of iron status that are frequently affected by inflammation, chronic diseases, and in the normal aging process (except soluble transferrin receptor). All are less available compared to complete blood count with reticulocyte hemoglobin content (CHr). Reticulocytes have a normal life span of one or two days in the circulation. CHr is a good indication of iron availability and an early marker of iron deficient erythropoiesis which can be obtained readily using automated blood cell analyzers. Therefore, the main objective of the current review is to assess the role of CHr for diagnosis of iron deficiency, iron deficiency anemia, and monitoring of iron therapy. METHODS: Studies published in English were searched using the National Library of Medicine, PubMed, and Google scholar databases. RESULTS: According to this review, CHr has a moderate sensitivity and specificity for diagnosing iron deficiency, and is less affected by inflammation than serum iron, transferrin saturation, and ferritin and is an early predictor of treatment response. It is used in screening of iron deficiency, diagnosis of iron deficiency anemia, and diagnosis of functional iron deficiency anemia in acute or chronic diseases or inflammation. CHr is also important in treatment monitoring. It is useful for early measurement of response to iron therapy, increasing within days of the initiation of iron therapy. It helps monitoring of intravenous iron supplementation, recombinant human erythropoie¬tin therapy, and oral iron therapy in hemodialysis and non-hemodialysis patients, and children. CONCLUSIONS: It is easy to analyze, less time consuming, and less expensive than bone iron examination and iron biochemical tests. However, there is no standardized cutoff point and different researchers use varying cutoff values which affects its accuracy in diagnosing iron deficiency and it should therefore be standardized. Moreover, since CHr can be affected with any conditions that cause iron restricted erythropoiesis, further analysis may be needed.

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  • Based on real-life evidence, determination of iron status by using serum ferritin and transferrin saturation is the most commonly deployed strategy used in clinical and public health settings.

    “Although many laboratory indexes may be helpful for the ID differential diagnostic workup, such as the mean corpuscular volume (MCV), the reticulocyte count and reticulocyte Hb content, the soluble transferrin receptor and its correlation with SF, and hepcidin measurement, based on the real-life evidence, the determination of iron status by using SF and TSAT is the most commonly deployed strategy”

    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 [18]

  • It is usual practice in many specialties and guidelines to assume that, regardless of the lower normality value of the ferritin test used, SF <30 ng/mL (irrespective of TSAT) or SF <100 ng/mL and TSAT <20% are the hallmarks of absolute iron deficiency; while SF >100 ng/mL and TSAT <20% usually indicate anemia of inflammation in the context of infection or inflammation.

    “It is a usual practice in many specialties and guidelines to assume that, regardless of the lower normality value of the ferritin test used, SF <30 ng/mL (irrespective of the TSAT value) or SF <100 ng/mL and TSAT <20% are the hallmarks of absolute ID; while SF >100 ng/mL and TSAT <20% usually indicate AI in the context of infection or inflammation [1,2,15,16,17,18,19,20].”

    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 [18]

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Authors
Gelaw, Y., Woldu, B., & Melku, M.
ORCID
Venue
Clinical Laboratory
Publisher
Clinical Laboratory Publications
Published
2019
Volume
65
Issue
12/2019
ISSN
1433-6510 (ISSN-L)
DOI
10.7754/clin.lab.2019.190315
OpenAlex
W2994611123
Cited by
50
References
0
Citations by year
2026: 5 · 2025: 7 · 2024: 7 · 2023: 13 · 2022: 9 · 2021: 5 · 2020: 4
FWCI
3.20
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Laboratory (publishedVersion)
  • PubMed (publishedVersion)
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
reticulocyte hemoglobin content, iron deficiency, iron deficiency anemia, iron status biomarkers, hemodialysis patients, recombinant human erythropoietin, iron deficiency screening
MeSH terms
Iron Deficiencies, Adult, Ferritins, Hemoglobins, Humans, Infant, Iron, Reticulocytes, Sensitivity and Specificity, Biomarkers, Anemia, Iron-Deficiency

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