Skip to main content
Top
Published in: International Journal of Hematology 4/2021

01-04-2021 | Erythrocyte Transfusion | Original Article

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

Authors: Ayako Ishihara, Tsuyuko Yamauchi, Katsuyoshi Ikeda, Yoko Fukuyoshi, Toshiro Yokoyama, Yuji Yonemura, Mitsuhiro Uchiba, Hirotaka Matsui

Published in: International Journal of Hematology | Issue 4/2021

Login to get access

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.
Appendix
Available only for authorised users
Literature
2.
go back to reference 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.CrossRef 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.CrossRef
4.
go back to reference Zhang AS, Enns CA. Iron homeostasis: recently identified proteins provide insight into novel control mechanisms. J Biol Chem. 2009;284:711–5.CrossRef Zhang AS, Enns CA. Iron homeostasis: recently identified proteins provide insight into novel control mechanisms. J Biol Chem. 2009;284:711–5.CrossRef
5.
go back to reference Coates TD. Iron overload in transfusion-dependent patients. Hematol Am Soc Hematol Educ Program. 2019;2019:337–44.CrossRef Coates TD. Iron overload in transfusion-dependent patients. Hematol Am Soc Hematol Educ Program. 2019;2019:337–44.CrossRef
6.
go back to reference Gattermann N. Iron overload in myelodysplastic syndromes (MDS). Int J Hematol. 2018;107:55–63.CrossRef Gattermann N. Iron overload in myelodysplastic syndromes (MDS). Int J Hematol. 2018;107:55–63.CrossRef
7.
go back to reference 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.CrossRef 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.CrossRef
8.
go back to reference Fernandes JL. Iron chelation therapy in the management of transfusion-related cardiac iron overload. Transfusion. 2012;52:2256–68.CrossRef Fernandes JL. Iron chelation therapy in the management of transfusion-related cardiac iron overload. Transfusion. 2012;52:2256–68.CrossRef
9.
go back to reference 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.CrossRef 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.CrossRef
10.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference 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.CrossRef 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.CrossRef
12.
go back to reference 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.CrossRef 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.CrossRef
13.
go back to reference 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.CrossRef 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.CrossRef
14.
go back to reference 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.CrossRef 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.CrossRef
15.
go back to reference Worwood M, Cragg SJ, Wagstaff M, Jacobs A. Binding of human serum ferritin to concanavalin A. Clin Sci (Lond). 1979;56:83–7.CrossRef Worwood M, Cragg SJ, Wagstaff M, Jacobs A. Binding of human serum ferritin to concanavalin A. Clin Sci (Lond). 1979;56:83–7.CrossRef
16.
go back to reference Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. Int Immunol. 2017;29:401–9.CrossRef Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. Int Immunol. 2017;29:401–9.CrossRef
17.
go back to reference 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.CrossRef 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.CrossRef
18.
go back to reference 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.PubMed 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.PubMed
19.
go back to reference 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.PubMed 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.PubMed
20.
go back to reference 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.CrossRef 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.CrossRef
21.
go back to reference Harrison PM, Arosio P. The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta. 1996;1275:161–203.CrossRef Harrison PM, Arosio P. The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta. 1996;1275:161–203.CrossRef
22.
go back to reference Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV. Serum ferritin: past, present and future. Biochim Biophys Acta. 2010;1800:760–9.CrossRef Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV. Serum ferritin: past, present and future. Biochim Biophys Acta. 2010;1800:760–9.CrossRef
23.
go back to reference Torti FM, Torti SV. Regulation of ferritin genes and protein. Blood. 2002;99:3505–16.CrossRef Torti FM, Torti SV. Regulation of ferritin genes and protein. Blood. 2002;99:3505–16.CrossRef
24.
go back to reference 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.CrossRef 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.CrossRef
25.
go back to reference 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 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
26.
go back to reference Henninger B, Alustiza J, Garbowski M, Gandon Y. Practical guide to quantification of hepatic iron with MRI. Eur Radiol. 2020;30:383–93.CrossRef Henninger B, Alustiza J, Garbowski M, Gandon Y. Practical guide to quantification of hepatic iron with MRI. Eur Radiol. 2020;30:383–93.CrossRef
27.
go back to reference 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.CrossRef 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.CrossRef
28.
go back to reference Worwood M, Cragg SJ, Williams AM, Wagstaff M, Jacobs A. The clearance of 131I-human plasma ferritin in man. Blood. 1982;60:827–33.CrossRef Worwood M, Cragg SJ, Williams AM, Wagstaff M, Jacobs A. The clearance of 131I-human plasma ferritin in man. Blood. 1982;60:827–33.CrossRef
29.
go back to reference 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.CrossRef 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.CrossRef
Metadata
Title
Glycosylated ferritin as an improved marker for post-transfusion iron overload
Authors
Ayako Ishihara
Tsuyuko Yamauchi
Katsuyoshi Ikeda
Yoko Fukuyoshi
Toshiro Yokoyama
Yuji Yonemura
Mitsuhiro Uchiba
Hirotaka Matsui
Publication date
01-04-2021
Publisher
Springer Singapore
Published in
International Journal of Hematology / Issue 4/2021
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-020-03056-9

Other articles of this Issue 4/2021

International Journal of Hematology 4/2021 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine