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Glycosylated ferritin as an improved marker for post-transfusion iron overload

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Abstract

Red blood cell (RBC) transfusion is an effective therapy for anemia, but repeated transfusions may cause iron overload-related damage to various organs. Iron chelation therapy, now widely available for patients who have received transfusions, is expected to reduce organ damage even in patients who received many transfusions. Therefore, determining when to start iron chelation therapy is important. In guidelines for iron chelation therapy, the serum ferritin level has been widely accepted as a practical marker for estimating iron overload. However, guidelines recommend multiple measurements of serum ferritin, because levels often fluctuate. Here, we investigated the usefulness of glycosylated ferritin as a marker of iron overload using a cohort consisted of 103 patients who had a total ferritin value over 1000 ng/mL. We found that the volume of RBCs transfused was clearly associated with the glycosylated ferritin level. We also found that acute inflammation, as represented by C-reactive protein values, was associated with increased non-glycosylated ferritin and that patients with hematopoietic diseases had higher glycosylated ferritin levels, possibly because of repeated RBC transfusions. We thus conclude that glycosylated ferritin may be an improved marker for predicting iron overload status.

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References

  1. U.S. Department of Agriculture ARS. What We Eat in America, NHANES, 2009-2010. U.S. Dept Agric Research Serv [Internet]. 2012; (July):2009–10. https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/1516/Table_1_NIN_GEN_15.pdf. Accessed 15 Dec 2020.

  2. Fujiwara A, Okada E, Okada C, Matsumoto M, Takimoto H. Association between free sugars intake and nutrient dilution among Japanese adults: the 2016 National Health and Nutrition Survey, Japan. Eur J Nutr. 2020;59:3827–39.

    Article  CAS  Google Scholar 

  3. Ems T, St Lucia K, Huecker MR. Biochemistry, iron absorption [Updated 2020 Apr 30]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2020. https://www.ncbi.nlm.nih.gov/books/NBK448204/. Accessed 15 Dec 2020.

  4. Zhang AS, Enns CA. Iron homeostasis: recently identified proteins provide insight into novel control mechanisms. J Biol Chem. 2009;284:711–5.

    Article  CAS  Google Scholar 

  5. Coates TD. Iron overload in transfusion-dependent patients. Hematol Am Soc Hematol Educ Program. 2019;2019:337–44.

    Article  Google Scholar 

  6. Gattermann N. Iron overload in myelodysplastic syndromes (MDS). Int J Hematol. 2018;107:55–63.

    Article  CAS  Google Scholar 

  7. Leitch HA, Buckstein R, Zhu N, Nevill TJ, Yee KWL, Leber B, et al. Iron overload in myelodysplastic syndromes: evidence based guidelines from the Canadian consortium on MDS. Leuk Res. 2018;74:21–41.

    Article  CAS  Google Scholar 

  8. Fernandes JL. Iron chelation therapy in the management of transfusion-related cardiac iron overload. Transfusion. 2012;52:2256–68.

    Article  CAS  Google Scholar 

  9. Takatoku M, Uchiyama T, Okamoto S, Kanakura Y, Sawada K, Tomonaga M, et al. Retrospective nationwide survey of Japanese patients with transfusion-dependent MDS and aplastic anemia highlights the negative impact of iron overload on morbidity/mortality. Eur J Haematol. 2007;78:487–94.

    Article  CAS  Google Scholar 

  10. Suzuki T, Tomonaga M, Miyazaki Y, Nakao S, Ohyashiki K, Matsumura I, et al. Japanese epidemiological survey with consensus statement on Japanese guidelines for treatment of iron overload in bone marrow failure syndromes. Int J Hematol. 2008;88:30–5.

    Article  CAS  Google Scholar 

  11. Jang JH, Lee JH, Yoon SS, Jo DY, Kim HJ, Chung J, et al. Korean guideline for iron chelation therapy in transfusion-induced iron overload. J Korean Med Sci. 2013;28:1563–72.

    Article  CAS  Google Scholar 

  12. Ho PJ, Tay L, Lindeman R, Catley L, Bowden DK. Australian guidelines for the assessment of iron overload and iron chelation in transfusion-dependent thalassaemia major, sickle cell disease and other congenital anaemias. Intern Med J. 2011;41:516–24.

    Article  CAS  Google Scholar 

  13. Cullis JO, Fitzsimons EJ, Griffiths WJ, Tsochatzis E, Thomas DW. Investigation and management of a raised serum ferritin. Br J Haematol. 2018;181:331–40.

    Article  Google Scholar 

  14. Rosário C, Zandman-Goddard G, Meyron-Holtz EG, D’Cruz DP, Shoenfeld Y. The hyperferritinemic syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome. BMC Med. 2013;11:185.

    Article  Google Scholar 

  15. Worwood M, Cragg SJ, Wagstaff M, Jacobs A. Binding of human serum ferritin to concanavalin A. Clin Sci (Lond). 1979;56:83–7.

    Article  CAS  Google Scholar 

  16. Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. Int Immunol. 2017;29:401–9.

    Article  CAS  Google Scholar 

  17. Fardet L, Coppo P, Kettaneh A, Dehoux M, Cabane J, Lambotte O. Low glycosylated ferritin, a good marker for the diagnosis of hemophagocytic syndrome. Arthritis Rheum. 2008;58:1521–7.

    Article  CAS  Google Scholar 

  18. Lambotte O, Cacoub P, Costedoat N, Le Moel G, Amoura Z, Piette JC. High ferritin and low glycosylated ferritin may also be a marker of excessive macrophage activation. J Rheumatol. 2003;30:1027–8.

    CAS  PubMed  Google Scholar 

  19. Fautrel B, Le Moël G, Saint-Marcoux B, Taupin P, Vignes S, Rozenberg S, et al. Diagnostic value of ferritin and glycosylated ferritin in adult onset Still’s disease. J Rheumatol. 2001;28:322–9.

    CAS  PubMed  Google Scholar 

  20. Moore C Jr, Ormseth M, Fuchs H. Causes and significance of markedly elevated serum ferritin levels in an academic medical center. J Clin Rheumatol. 2013;19:324–8.

    Article  Google Scholar 

  21. Harrison PM, Arosio P. The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta. 1996;1275:161–203.

    Article  Google Scholar 

  22. Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV. Serum ferritin: past, present and future. Biochim Biophys Acta. 2010;1800:760–9.

    Article  CAS  Google Scholar 

  23. Torti FM, Torti SV. Regulation of ferritin genes and protein. Blood. 2002;99:3505–16.

    Article  CAS  Google Scholar 

  24. Nash S, Marconi S, Sikorska K, Naeem R, Nash G. Role of liver biopsy in the diagnosis of hepatic iron overload in the era of genetic testing. Am J Clin Pathol. 2002;118:73–81.

    Article  Google Scholar 

  25. Ruefer A, Bapst C, Benz R, Bremerich J, Cantoni N, Infanti L, et al. Role of liver magnetic resonance imaging in hyperferritinaemia and the diagnosis of iron overload. Swiss Med Wkly. 2017;147:w14550.

    PubMed  Google Scholar 

  26. Henninger B, Alustiza J, Garbowski M, Gandon Y. Practical guide to quantification of hepatic iron with MRI. Eur Radiol. 2020;30:383–93.

    Article  Google Scholar 

  27. Santambrogio P, Cozzi A, Levi S, Arosio P. Human serum ferritin G-peptide is recognized by anti-L ferritin subunit antibodies and concanavalin-A. Br J Haematol. 1987;65:235–7.

    Article  CAS  Google Scholar 

  28. Worwood M, Cragg SJ, Williams AM, Wagstaff M, Jacobs A. The clearance of 131I-human plasma ferritin in man. Blood. 1982;60:827–33.

    Article  CAS  Google Scholar 

  29. Cohen LA, Gutierrez L, Weiss A, Leichtmann-Bardoogo Y, Zhang DL, Crooks DR, et al. Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood. 2010;116:1574–84.

    Article  CAS  Google Scholar 

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Correspondence to Hirotaka Matsui.

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Ishihara, A., Yamauchi, T., Ikeda, K. et al. Glycosylated ferritin as an improved marker for post-transfusion iron overload. Int J Hematol 113, 537–546 (2021). https://doi.org/10.1007/s12185-020-03056-9

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  • DOI: https://doi.org/10.1007/s12185-020-03056-9

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