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Serum Transferrin Receptor and Its Ratio to Serum Ferritin in the Diagnosis of Iron Deficiency
Open accessAbstract
The objective of the study was to evaluate the diagnostic efficiency of laboratory tests, including serum transferrin receptor (TfR) measurements, in the diagnosis of iron depletion. The patient population consisted of 129 consecutive anemic patients at the University Hospital of Turku who were given a bone marrow examination. Of these patients, 48 had iron deficiency anemia (IDA), 64 anemia of chronic disease (ACD), and 17 patients had depleted iron stores and an infectious or an inflammatory condition (COMBI). Depletion of iron stores was defined as a complete absence of stainable iron in the bone marrow examination. Serum TfR concentrations were elevated in the vast majority of the IDA and COMBI patients, while in the ACD patients, the levels were within the reference limits reported earlier for healthy subjects. TfR measurement thus provided a reliable diagnosis of iron deficiency anemia (AUCROC 0.98). Serum ferritin measurement also distinguished between IDA patients and ACD patients. However, the optimal decision limit for evaluation of ferritin measurements was considerably above the conventional lower reference limits, complicating the interpretation of this parameter. Calculation of the ratio TfR/log ferritin (TfR-F Index) is a way of combining TfR and ferritin results. This ratio provided an outstanding parameter for the identification of patients with depleted iron stores (AUCROC 1.00). In anemic patients, TfR measurement is a valuable noninvasive tool for the diagnosis of iron depletion, and offers an attractive alternative to more conventional laboratory tests in the detection of depleted iron stores.
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“Steady-state levels of hemoglobin and hematocrit in healthy adults typically correlate negatively with log 10 EPO levels (21).”
From Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point (2014) · cites this paper as [21]
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“In their study, the log ferritin/soluble transferrin receptor ratio was used to categorize patients as having either anemia of chronic disease (ACD) or ACD with iron deficiency anemia (ACD/IDA), as the ratio has been demonstrated to discriminate ACD from ACD/IDA appropriately [69].”
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“Additionally, TfRF index has been suggested to be a sensitive indicator of iron deficiency [21,22] and a statistically significant positive correlation was found also between EPO and TfR-F index.”
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Zhu, Y., Liu, X., Li, N., Lingling, C., Zhang, X., Liu, X., Yu, K., Chen, Y., Wan, Z., & Yu, Z. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2019.00303 · Cited by 14
“It has been suggested that sTfR/ferritin index is a good estimate of body iron (26, 27).”
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“The receptor synthesis is induced by the depletion of intracellular iron (4, 7, 8), and elevated serum TfR has proved to be a sensitive indicator of depletion of iron stores (3, 9, 10).”
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Nutrigenomics and Trace Elements: Hopes and Hypes for Parkinson’s Treatment
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“These are a simple ratio (sTfR/SF) [61], the ratio of sTfR to the log of SF [62], or the body iron index [57].”
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“It is also worth mentioning, that calculation of the sTfR-F index (obtained by division of sTfR into log ferritin) may diagnose iron deficiency more accurately, because in the total obtained from this formula, two values of ferritin (iron index stored in the body) and sTfR (transferred iron index of the body) are invo…”
BackgroundCongestive heart failure-related anemia and a role for erythropoietin
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Velasco‐Rodríguez, D., Alonso‐Domínguez, J. M., González-Fernández, F.-A., Villarrubia, J., Sopeña, M., Abalo, L., Ropero, P., Nieto, J. M., de la Fuente-Gonzalo, F., & Cava, F. (2015) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2015-203034 · Cited by 12
Challenges in routine clinical chemistry analysis
Sepulveda, J. L. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813776-5.00010-8 · Cited by 12
Evanchuk, J. L., Kozyrskyj, A. L., Hanas, N., Goruk, S., Vaghef-Mehrabani, E., Archundia-Herrera, C. M., O'Brien, K. O., Letourneau, N. L., Giesbrecht, G. F., Bell, R. C., et al. (2023) · Journal of Nutrition · doi:10.1016/j.tjnut.2023.06.042 · Cited by 12
Caterina, M. D., Grimaldi, E., Pascale, G. D., Salerno, G., Rosiello, A., Passaretti, M., & Scopacasa, F. (2005) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2005.005 · Cited by 11
Ong, K. H., Tan, H. L., Tam, L., Hawkins, R. C., & Kuperan, P. (2007) · International Journal of Laboratory Hematology · doi:10.1111/j.1751-553x.2007.00982.x · Cited by 12
Increased hepcidin expression in multibacillary leprosy
de Souza, V. N. B., Malaspina, T. S. D. S., Campanelli, A. P., Ghidella, C. C., Ura, S., Dalpino, D., do Nascimento, D. C., & Latini, A. C. P. (2012) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/s0074-02762012000900026 · Cited by 12
“The serum levels of ferritin were largely used to describe AI, since they are increased in this condition, while in IDA they are diminished.”
BackgroundResultInfluentialEvaluation of reticulocyte hemoglobin for assessment of anemia in rheumatological disorders
Singh, B. G., Duggal, L., Jain, N. K., Chaturvedi, V. P., Patel, J., & Kotwal, J. (2019) · International Journal of Rheumatic Diseases · doi:10.1111/1756-185x.13567 · Cited by 12
Fiorentino, M., Pérignon, M., Kuong, K., Chamnan, C., Berger, J., & Wieringa, F. T. (2018) · Public Health Nutrition · doi:10.1017/s1368980017003809 · Cited by 12
“Other studies, however, showed a significant impact of the APR on TfR values((11,12)).”
BackgroundEvaluation of serum transferrin receptor assay in a centralized iron screening service
O’Broin, S. D., Kelleher, B., Balfe, Á., & Mahon, C. (2005) · Clinical & Laboratory Haematology · doi:10.1111/j.1365-2257.2005.00680.x · Cited by 12
The Anemia of Inflammation and Chronic Disease
Roy, C. N. (2011) · Humana Press eBooks · doi:10.1007/978-1-60327-485-2_15 · Cited by 12
Ruivard, M., Boursiac, M., Mareynat, G., Sapin, A.-F. S., Gerbaud, L., Derumeaux, H., Fouilhoux, A., Travade, P., & Philippe, P. (2000) · La Revue de Médecine Interne · doi:10.1016/s0248-8663(00)00234-4 · Cited by 12
Iron Depletion without Anemia Is Not Associated with Impaired Selenium Status in College-Aged Women
McAnulty, L. S., Gropper, S. S., McAnulty, S. R., & Keith, R. E. (2003) · Biological Trace Element Research · doi:10.1385/bter:91:2:125 · Cited by 12
Bjerner, J., Amlie, L. M., Rusten, L. S., & Jakobsen, E. (2002) · Tumor Biology · doi:10.1159/000064031 · Cited by 12
Katodritou, E., Speletas, M. G., Zervas, K., Kapetanos, D., Georgiou, E., Christoforidou, A., Pavlitou, A., Sion, M. L., & Christakis, J. I. (2006) · Laboratory Hematology · doi:10.1532/lh96.05030 · Cited by 12
The African enigma: the parasite's perspective
Fox, J. G., Wang, T. C., & Nagler‐Anderson, C. (2001) · Gut · doi:10.1136/gut.49.1.156a · Cited by 12
Anemia of chronic diseases: current state of the problem and perspectives
Mironova, O. I., & Panferov, A. S. (2023) · Terapevticheskii arkhiv · doi:10.26442/00403660.2022.12.201984 · Cited by 11
The Top 100 Cited Papers in the Field of Iron Deficiency in Humans: A Bibliometric Study
Frater, J. L. (2021) · BioMed Research International · doi:10.1155/2021/5573790 · Cited by 13
“The ratio of serum transferrin receptor to serum ferritin, a potentially useful laboratory test for whole body iron stores, is limited by lack of standardization of serum transferrin receptor assays [53, 57, 58].”
BackgroundKamer, B., Dółka, E., Pasowska, R., & Świątkowska, E. (2012) · Folia Histochemica et Cytobiologica · doi:10.5603/19760 · Cited by 11
“[30], in turn, while examining adults with iron deficiency anemia, found that in 95% of cases lowered serum ferritin concentrations correctly identified iron deficiency, as confirmed by bone marrow biopsy.”
BackgroundNadeem, S., Shah, S., Iqbal, T., Iqbal, Z., & Hanif, E. (2011) · PubMed · Cited by 11
Takala, T. I., Suominen, P., Lehtonen-Veromaa, M. K., Möttönen, T. T., Viikari, J. S. A., Rajamäki, A., & Irjala, K. M. A. (2003) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2003.033 · Cited by 11
Self-citationTransferrin receptor level as surrogate peripheral blood marker of iron deficiency states
Koulaouzidis, A., Saeed, A. A., Abdallah, M., & Said, E. (2008) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365520802555983 · Cited by 11
“TO THE EDITOR: The level of soluble transferrin receptor (sTfR) and its ratio to Log10ferritin (sTfR/F Index) is thought to be a reliable marker of iron deficiency (nearly as reliable as bone marrow examination) [1].”
BackgroundVázquez-López, M. Á., López‐Ruzafa, E., Lendínez, F., Ortiz-Pérez, M., Tudela, L. R., & Martín-González, M. (2016) · Pediatric Hematology and Oncology · doi:10.3109/08880018.2015.1138007 · Cited by 12
“27 = 1 μg IBC/dL; transferrin saturation (TS) was calculated as serum iron/TIBC × 100; serum erythropoietin (sEPO) determined by enzyme immunoassay using the Quantikine IVD-Human Erythropoietin kit (R&D Systems, Minneapolis, MN, USA); serum transferrin receptor (sTfR) by immunoturbidimetric assay using the Quantex sTf…”
BackgroundMethodIron deficiency anemia, anemia of chronic disorders and iron overload
Pippard, M. J. (2011) · Elsevier eBooks · doi:10.1016/b978-0-7020-3147-2.00011-0 · Cited by 13
Iron deficiency anaemia and iron overload
Worwood, M. (2006) · Elsevier eBooks · doi:10.1016/b0-44-306660-4/50011-8 · Cited by 11
Incidence of anemia in older Koreans: Community-based cohort study
Choi, C. W., Lee, J., Park, K. H., Choi, I. K., Kim, S. J., Seo, J. H., Kim, B. S., Shin, S. W., Kim, Y. H., & Kim, J. S. (2005) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2005.04.007 · Cited by 11
Metadata
- Authors
- Punnonen, K., Irjala, K., & Rajamäki, A.
- Affiliations
- Turku University Hospital (FI)
- From the Central Laboratory, Departments of Clinical Chemistry and Hematology, University Hospital of Turku, Turku, Finland.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1997-02-01
- Volume
- 89
- Issue
- 3
- Pages
- 1052-1057
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1924847619
- Cited by
- 859
- References
- 28
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 19 · 2023: 20 · 2022: 10 · 2021: 26 · 2020: 29 · 2019: 25 · 2018: 37 · 2017: 22 · 2016: 28 · 2015: 44 · 2014: 35 · 2013: 30 · 2012: 45
- FWCI
- 13.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Hematological disorders and diagnostics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- serum transferrin receptor, serum ferritin, iron deficiency anemia, anemia of chronic disease, iron depletion, diagnostic accuracy, inflammatory diseases
- MeSH terms
- Adult, Anemia, Blood Cell Count, Bone Marrow, Chronic Disease, Female, Ferritins, Humans, Iron, Male, Receptors, Transferrin, Staining and Labeling, Anemia, Iron-Deficiency
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