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Reticulocyte hemoglobin equivalent as a potential marker for diagnosis of iron deficiency


Evaluation of parameters relating to serum ferritin and iron is critically important in the diagnosis of iron deficiency anemia (IDA). The recent development of automated systems for hematology analysis has made it possible to measure reticulocyte hemoglobin equivalent (RET-He), which is thought to reflect iron content in reticulocytes, in the same sample used for complete blood count tests. If RET-He is, indeed, capable of evaluating iron deficiency (ID), it would be useful for immediate diagnosis of IDA. In the present study, we examined the usefulness of RET-He for diagnosis of ID. Blood samples were obtained from 211 patients. Anemia was defined as hemoglobin (Hb) level of <12 g/dL. Iron deficiency was defined as serum ferritin level of <12 ng/mL. Patients were classified into four groups: IDA, ID, control, and non-ID with anemia. Patients in the IDA group had significantly lower RET-He levels than those in the control group. RET-He correlated with serum ferritin in the IDA and ID groups. The area under the curve for RET-He was 0.902, indicating that RET-He facilitates the diagnosis of ID with high accuracy. RET-He changed in parallel with changes in Hb during iron administration for 21 IDA patients. Our results indicate that RET-He may be a clinically useful marker for determining ID in the general population.

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  1. 1.

    Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L. Iron deficiency anaemia. Lancet. 2016;387:907–16.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    World Health Organization. Haemoglobin concentrations for the diagnosis of aneamia and assessment of severity: World Health Organization; 2011. WHO reference number: WHO/NMH/NHD/MNM/11.1.

  3. 3.

    Mei Z, Cogswell ME, Looker AC, Pfeiffer CM, Cusick SE, Lacher DA, et al. Assessment of iron status in US pregnant women from the National Health and Nutrition Examination Survey (NHANES), 1999–2006. Am J Clin Nutr. 2011;93:1312–20.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N, Lozano R, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014;123:615–24.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Guyatt GH, Oxman AD, Ali M, Willan A, McIlroy W, Patterson C. Laboratory diagnosis of iron-deficiency anemia: an overview. J Gen Intern Med. 1992;7:145–53.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Brugnara C, Laufer MR, Friedman AJ, Bridges K, Platt O. Reticulocyte hemoglobin content (CHr): early indicator of iron deficiency and response to therapy. Blood. 1994;83:3100–1.

    CAS  PubMed  Google Scholar 

  7. 7.

    Buttarello M, Temporin V, Ceravolo R, Farina G, Bulian P. The new reticulocyte parameter (RET-Y) of the Sysmex XE 2100: its use in the diagnosis and monitoring of posttreatment sideropenic anemia. Am J Clin Pathol. 2004;121:489–95.

    Article  PubMed  Google Scholar 

  8. 8.

    Brugnara C, Schiller B, Moran J. Reticulocyte hemoglobin equivalent (Ret He) and assessment of iron-deficient states. Clin Lab Haematol. 2006;28:303–8.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Torsvik IK, Markestad T, Ueland PM, Nilsen RM, Midttun O, Bjørke Monsen AL. Evaluating iron status and the risk of anemia in young infants using erythrocyte parameters. Pediatr Res. 2013;73:214–20.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Semmelrock MJ, Raggam RB, Amrein K, Avian A, Schallmoser K, Lanzer G, et al. Reticulocyte hemoglobin content allows early and reliable detection of functional iron deficiency in blood donors. Clin Chim Acta. 2012;413:678–82.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Joosten E, Lioen P, Brusselmans C, Indevuyst C, Boeckx N. Is analysis of the reticulocyte haemoglobin equivalent a useful test for the diagnosis of iron deficiency anaemia in geriatric patients? Eur J Intern Med. 2013;24:63–6.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Schoorl M, Schoorl M, van der Gaag D, Bartels PC. Effects of iron supplementation on red blood cell hemoglobin content in pregnancy. Hematol Rep. 2012;4:e24.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Miwa N, Akiba T, Kimata N, Hamaguchi Y, Arakawa Y, Tamura T, et al. Usefulness of measuring reticulocyte hemoglobin equivalent in the management of haemodialysis patients with iron deficiency. Int J Lab Hematol. 2010;32:248–55.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Ali MA, Luxton AW, Walker WH. Serum ferritin concentration and bone marrow iron stores: a prospective study. Can Med Assoc J. 1978;118:945–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Mast AE, Blinder MA, Gronowski AM, Chumley C, Scott MG. Clinical utility of the soluble transferrin receptor and comparison with serum ferritin in several populations. Clin Chem. 1998;44:45–51.

    CAS  PubMed  Google Scholar 

  16. 16.

    Piva E. Comment on: Evaluation of erythrocyte and reticulocyte parameters as indicative of iron deficiency in patients with anemia of chronic disease. Rev Bras Hematol Hemoter. 2015;37:73–6.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Miano M, Dufour C. The diagnosis and treatment of aplastic anemia: a review. Int J Hematol. 2015;101:527–35.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Skikne BS, Flowers CH, Cook JD. Serum transferrin receptor: a quantitative measure of tissue iron deficiency. Blood. 1990;75:1870–6.

    CAS  PubMed  Google Scholar 

  19. 19.

    Infusino I, Braga F, Dolci A, Panteghini M. Soluble transferrin receptor (sTfR) and sTfR/log ferritin index for the diagnosis of iron-deficiency anemia. A meta-analysis. Am J Clin Pathol. 2012;138:642–9.

    Article  PubMed  Google Scholar 

  20. 20.

    Thomas DW, Hinchliffe RF, Briggs C, Macdougall IC, Littlewood T, Cavill I. Guideline for the laboratory diagnosis of functional iron deficiency. Br J Haematol. 2013;161:639–48.

    CAS  Article  PubMed  Google Scholar 

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Author contribution

Study concept and design: YT, KI, MF, and TO. Laboratory analysis: YT, KI, YK, NN, MK, ME, SI, and YT. Statistical analysis and interpretation of data: YT and KI. Obtaining informed consent, sample collection, and analysis of medical data: YT, KI, MH, MY, MS, YK, MI, and KS. Manuscript preparation: YT and KI.

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Correspondence to Katsuya Ikuta.

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Conflict of interest

Yasumichi Toki, Katsuya Ikuta, Mayumi Hatayama, Masayo Yamamoto, Motohiro Shindo, Mikihiro Fujiya, Toshikatsu Okumura (Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University), Masayoshi Kon, Kazuya Sato (Asahikawa-Kosei General Hospital), Motoki Enomoto, Mitsutaka Inoue (Engaru-Kosei General Hospital), Yuko Tada, and Yoko Kikuchi (Moriyama Hospital) received research funding from Sysmex Corporation. This study was also performed in collaboration with Sysmex Corporation. Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University also received collaborative research funding for research work concerning iron metabolism from Chugai Pharmaceutical Co. Ltd., Novartis Pharma K. K., Asahi Kasei Medical Co. Ltd., Shino-Test Corporation and USHIO INC. Yoshie Kawahara and Noriyasu Niizeki have no conflict of interests to declare.

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Toki, Y., Ikuta, K., Kawahara, Y. et al. Reticulocyte hemoglobin equivalent as a potential marker for diagnosis of iron deficiency. Int J Hematol 106, 116–125 (2017).

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  • Reticulocyte hemoglobin equivalent (RET-He)
  • Iron deficiency anemia
  • Iron
  • Iron deficiency
  • Diagnosis