Serum Transferrin Receptor and Its Ratio to Serum Ferritin in the Diagnosis of Iron Deficiency
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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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Oral Iron Supplementation After Blood Donation
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“Time to recovery of baseline ferritin levels, median (IQR), d 21 (12-84) >168 (128->168) 107 (75-141) >168 (>168->168)”
Khalafallah, A. A., & Dennis, A. E. (2012) · Journal of Pregnancy · doi:10.1155/2012/630519 · Cited by 166 · see citing works
“Soluble TfR (sTfR) is present in human plasma and is considered as a truncated form of the tissue receptor that exists as a transferrin-receptor complex and therefore it reflects tissue iron deficiency [21].”
Nairz, M., Theurl, I., Wolf, D., & Weiss, G. (2016) · Wiener Medizinische Wochenschrift · doi:10.1007/s10354-016-0505-7 · Cited by 152 · see citing works
The relationship between obesity and hypoferraemia in adults: A systematic review
Cheng, H. L., Bryant, C., Cook, R., O'Connor, H., Rooney, K., & Steinbeck, K. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2011.00938.x · Cited by 159 · see citing works
“Other measurements such as the sTfR–ferritin index have also been reported to be valuable indicators of iron status in this circumstance (49,50).”
BackgroundIron, zinc, and copper in retinal physiology and disease
Ugarte, M., Osborne, N. N., Brown, L. A., & Bishop, P. N. (2013) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2012.12.002 · Cited by 157 · see citing works
Lanser, L., Fuchs, D., Kurz, K., & Weiß, G. (2021) · Nutrients · doi:10.3390/nu13113732 · Cited by 166 · see citing works
Anemia Is Associated With Depression in Older Adults: Results From the InCHIANTI Study
Onder, G., Penninx, B. W. J. H., Cesari, M., Bandinelli, S., Lauretani, F., Bartali, B., Gori, A. M., Pahor, M., & Ferrucci, L. (2005) · The Journals of Gerontology Series A · doi:10.1093/gerona/60.9.1168 · Cited by 153 · see citing works
“5 was used to define iron deficiency (20).”
MethodReticulocyte hemoglobin content
Mast, A. E., Blinder, M. A., & Dietzen, D. J. (2007) · American Journal of Hematology · doi:10.1002/ajh.21090 · Cited by 151 · see citing works
Skikne, B. (2008) · American Journal of Hematology · doi:10.1002/ajh.21279 · Cited by 148 · see citing works
“anemia of chronic disease, as well as combined anemia of chronic disease plus iron deficiency (COMBI) from anemia of chronic disease alone [29].”
BackgroundStructure, Function and Clinical Significance of Transferrin Receptors
Feelders, R. A., Kuiper-Kramer, E. P. A., & van Eijk, H. G. (1999) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.1999.001 · Cited by 148 · see citing works
“evaluated sTfR levels in 129 consecutive anaemic patients undergoing bone marrow examination for stainable iron content (86).”
BackgroundAnaemia in inflammatory rheumatic diseases
Weiss, G., & Schett, G. (2013) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2012.183 · Cited by 146 · see citing works
Tay, E. L. W., Peset, A. M., Papaphylactou, M., Inuzuka, R., Alonso-González, R., Giannakoulas, G. A., Tzifa, A., Goletto, S., Broberg, C. S., Dimopoulos, K., et al. (2010) · International Journal of Cardiology · doi:10.1016/j.ijcard.2010.05.066 · Cited by 146 · see citing works
Diagnosis and management of anaemia of chronic disease: current status
Cullis, J. (2011) · British Journal of Haematology · doi:10.1111/j.1365-2141.2011.08741.x · Cited by 144 · see citing works
“The ratio of sTFR to the log of the serum ferritin has been proposed to be a useful tool in the diagnosis of ACD, and particularly in differentiating ACD from IDA (Punnonen et al, 1997; Suominen et al, 2000; Malope et al, 2001; Skikne, 2008).”
MethodInfusino, I., Braga, F., Dolci, A., & Panteghini, M. (2012) · American Journal of Clinical Pathology · doi:10.1309/ajcp16ntxzlzfaib · Cited by 144 · see citing works
Garcia-Valdes, L., Campoy, C., Hayes, H. E., Florido, J., Rusanova, I., León, M. T. M., & McArdle, H. J. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.3 · Cited by 143 · see citing works
van Santen, S., van Dongen-Lases, E. C., de Vegt, F., Laarakkers, C. M., van Riel, P. L. C. M., van Ede, A. E., & Swinkels, D. W. (2011) · Arthritis & Rheumatism · doi:10.1002/art.30623 · Cited by 141 · see citing works
Prevalence of Iron Deficiency with and without Anemia in Recreationally Active Men and Women
Sinclair, L. M., & Hinton, P. S. (2005) · Journal of the American Dietetic Association · doi:10.1016/j.jada.2005.03.005 · Cited by 140 · see citing works
Iron and the endurance athlete
Hinton, P. S. (2014) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2014-0147 · Cited by 135 · see citing works
Iron deficiency in the elderly population, revisited in the hepcidin era
Busti, F., Campostrini, N., Martinelli, N., & Girelli, D. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00083 · Cited by 135 · see citing works
“In particular, the serum sTfR divided by the log of the ferritin (sTfR-ferritin index) was found useful in classifying patients with ACD and concomitant IDA (Punnonen et al., 1997; Rimon et al., 2002).”
MethodBeard, J. L., Murray‐Kolb, L. E., Rosales, F. J., Solomons, N. W., & Angelilli, M. L. (2006) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/84.6.1498 · Cited by 132 · see citing works
“The TfR-ferritin index was computed as the ratio of TfR to log ferritin (TfR/log ferritin) as previously reported (17, 18), and body iron was calculated by using the new approach of Cook et al (19).”
BackgroundMethodDiagnosis of Iron Deficiency Anemia in the Elderly by Transferrin Receptor–Ferritin Index
Rimon, E., Levy, S., Sapir, A., Gelzer, G., Peled, R., Ergas, D., & Sthoeger, Z. M. (2002) · Archives of Internal Medicine · doi:10.1001/archinte.162.4.445 · Cited by 129 · see citing works
“5 was considered diagnostic of iron deficiency.(24,28,29) All TR values herein are presented as TR-F index.”
BackgroundMethodInfluentialSerum or plasma ferritin concentration as an index of iron deficiency and overload
Garcia‐Casal, M. N., Pasricha, S., Martinez, R. X., Lopez-Perez, L., & Peña‐Rosas, J. P. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011817.pub2 · Cited by 132 · see citing works
Gupta, A. (2024) · Springer eBooks · doi:10.1007/978-981-99-8933-1_5 · Cited by 131 · see citing works
Iron Deficiency in Obese Postmenopausal Women
Lecube, A., Carrera, A., Losada, E., Hernández, C., Simó, R., & Mesa, J. (2006) · Obesity · doi:10.1038/oby.2006.198 · Cited by 130 · see citing works
“The ratio of the concentrations of sTfR to log ferritin (sTfR/log ferritin ratio) was used as an additional marker for biochemical identification of iron-deficient erythropoiesis (19,20).”
MethodDiagnosis of iron deficiency in chronic renal failure
Fernández-Rodríguez, A. M., Guindeo-Casasús, M. C., Molero-Labarta, T., Domínguez-Cabrera, C., Hortal-Cascón, L., Pérez-Borges, P., Vega-Díaz, N., Saavedra-Santana, P., & Palop-Cubillo, L. (1999) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(99)70079-x · Cited by 126 · see citing works
Parenteral iron therapy in obstetrics: 8 years experience with iron–sucrose complex
Perewusnyk, G., Huch, R., Huch, A., & Breymann, C. (2002) · British Journal Of Nutrition · doi:10.1079/bjn2002577 · Cited by 128 · see citing works
Girelli, D., Marchi, G., & Camaschella, C. (2018) · HemaSphere · doi:10.1097/hs9.0000000000000040 · Cited by 134 · see citing works
Þórsdóttir, I., Gunnarsson, B. S., Atladóttir, H. Ó., Michaelsen, K. F., & Palsson, G. (2003) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1601594 · Cited by 126 · see citing works
“When the TfR>8.5 mg=l is used as a cut-off (Asobayire et al, 2001), 25% of the infants in the present study have elevated TfR. Studies are needed on TfR and the TfR:log SF ratio, which have been suggested to depict the entire range of iron status (Punnonen et al, 1997; Skikne et al, 1990).”
MethodInfluentialIron deficiency in female pattern hair loss, chronic telogen effluvium, and control groups
Olsen, E. A., Reed, K. B., Cacchio, P. B., & Caudill, L. (2010) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2009.12.006 · Cited by 125 · see citing works
“Using serum ferritin levels as a marker for iron storage deficiency, the definition of ID (but not specifically IDA) in various studies has ranged from a serum ferritin of less than or equal to 15 g/L to less than 70 g/L.(14,16-20) The sensitivity of using serum ferritin of less than or equal to 15 g/L and less than o…”
Montonen, J., Boeing, H., Steffen, A., Lehmann, R., Fritsche, A., Joost, H.-G., Schulze, M. B., & Pischon, T. (2012) · Diabetologia · doi:10.1007/s00125-012-2633-y · Cited by 124 · see citing works
“Therefore, it has been suggested that the ratio of serum concentrations of sTfR and ferritin should be a preferred measure of body iron stores [18, 19, 37].”
BackgroundAnemia of chronic disease: pathophysiology and laboratory diagnosis.
THOMAS, C., & THOMAS, L. (2005) · Laboratory Hematology · doi:10.1532/lh96.04049 · Cited by 124 · see citing works
Long Term Outcome of Severe Anaemia in Malawian Children
Phiri, K. S., Calis, J. C. J., Faragher, B. E., Nkhoma, E., Kondwani, N., Mangochi, B., Molyneux, M. E., & van Hensbroek, M. B. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002903 · Cited by 120 · see citing works
“All laboratory assays were done in all study groups, unless otherwise stated and were blinded to patient study group where possible. Haemoglobin concentration was measured on site using the HemoCue B-Haemoglobin analyser (HemoCue, Angelholm, Sweden) and subsequently by Coulter counter analyser (Beckman Coulter, Durban…”
InfluentialIron deficiency without anemia – a clinical challenge
Soppi, E. T. (2018) · Clinical Case Reports · doi:10.1002/ccr3.1529 · Cited by 121 · see citing works
“Patients with true iron deficiency anemia on the basis of negative bone marrow iron staining may have a serum ferritin concentration close to 50 lg/L [7].”
BackgroundMeasurement of soluble transferrin receptor in serum of healthy adults
Allen, J., Backstrom, K. R., Cooper, J. A., Cooper, M. C., Detwiler, T. C., Essex, D. W., Fritz, R. P., Means, R. T., Meier, P. B., Pearlman, S. R., et al. (1998) · Clinical Chemistry · doi:10.1093/clinchem/44.1.35 · Cited by 121 · see citing works
“In iron deficiency, [sTfR] increases to about twice the normal concentration [16, 17], but the distribution of values is broad enough that the 95% ranges may overlap.”
BackgroundLiu, K., & Kaffes, A. J. (2011) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0b013e32834f3140 · Cited by 118 · see citing works
Dysregulated iron metabolism in polycythemia vera: etiology and consequences
Ginzburg, Y. Z., Feola, M., Zimran, E., Várkonyi, J., Ganz, T., & Hoffman, R. (2018) · Leukemia · doi:10.1038/s41375-018-0207-9 · Cited by 118 · see citing works
Biological and clinical aspects of soluble transferrin receptor
Speeckaert, M. M., Speeckaert, R., & Delanghe, J. (2010) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2010.550461 · Cited by 118 · see citing works
Hinton, P. S., & Sinclair, L. M. (2006) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602479 · Cited by 117 · see citing works
Classification of anemia for gastroenterologists
Chulilla, J. A. M., Colás, M. S. R., & Martín, M. G. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.4627 · Cited by 116 · see citing works
Jiang, Y., Jiang, F., Kong, F., An, M.-M., Jin, B.-B., Cao, D., & Gong, P. (2019) · Annals of Intensive Care · doi:10.1186/s13613-019-0542-7 · Cited by 118 · see citing works
- 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 › Emergency Medicine › 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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