About Iron Deficiency
Iron Deficiency

Functional Iron Deficiency

A functional iron deficiency exists when the total body iron stores are normal or decreased, but the iron supply to the bone marrow and other tissues is inadequate. The ultimate consequence of this functional disturbance of iron homeostasis is anemia. Absolute and functional deficiencies can coexist.9

Functional iron deficiency can be present in many acute and chronic inflammatory states. In these conditions, ferritin can apparently be normal or even increased, because inflammatory states are known to increase serum ferritin levels. Thus, the predictive value of ferritin is limited in inflammation as it is an acute phase protein.9

It is now known that hepcidin plays a key role in pathogenesis by controlling iron availability to tissues: in cases of acute or chronic inflammatory states or infection, hepcidin production and release is induced by circulating pro-inflammatory cytokines, especially interleukin-6. This results in increased internalization and degradation of ferroportin and subsequent cellular iron retention, which in turn blocks iron transportation into the circulation.5, 10

Funktioneller Eisenmangel

Characteristics of functional iron deficiency 5, 21

  • Normal to elevated serum ferritin (in case of inflammation)
  • Transferrin saturation <20%
  • Increased fraction of hypochromic erythrocytes and reticulocytes
  • Reduced mean erythrocyte volume (MCV) and reduced mean cellular hemoglobin (MCH)
  • Often less good response to oral iron therapy
  • Insufficient response of hemoglobin to erythropoiesis-stimulating substances (ESA).

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References

  1. Clénin GE. The treatment of iron deficiency without anaemia (in otherwise healthy persons). Swiss Med Wkly. 2017;147:w14434
  2. Musallam KM, Taher AT. Iron deficiency beyond erythropoiesis: should we be concerned? Curr Med Res Opin. 2018;34(1):81–93.
  3. Doom JR. Striking while the iron is hot: Understanding the biological and neurodevelopmental effects of iron deficiency to optimize intervention in early childhood. Curr Pediatr Rep. 2015;2(4):291–298
  4. Worldwide prevalence of anaemia 1993–2005. WHO The global prevalence of anaemia in 2011. Geneva: World Health Organization 2015
  5. Lopez A et al. Iron deficiency anaemia. Lancet 2016;387(10021):907–16
  6. Herklotz R and Huber A. Labordiagnose von Eisenstoffwechselstörungen. Schweiz Med Forum 2010;10(30–31):500–507
  7. Clénin et al. The treatment of iron deficiency without anaemia (in otherwise healthy persons). Swiss Med Wkly. 2017 Jun14;147:w14434
  8. Hercberg S, Preziosi P, Galan P. Iron deficiency in Europe. Public Health Nutr 2001; 4: 537–545
  9. Chrobak C et al. Iron homeostasis in inflammation: a single centre prospective observational study in medical inpatients. Swiss Med Wkly. 2017;147:w14431
  10. Muckenthaler MU et al. A red carpet for iron metabolism. Cell 2017;168(3):344–361
  11. Dignass A et al. Limitations of Serum Ferritin in Diagnosing Iron Deficiency in Inflammatory Conditions. Int J Chronic Dis. 2018 Mar 18;2018:9394060
  12. Crichton RR et al. Iron therapy with special emphasis on intravenous administration. UNI-MED 2008, 4th Edition, chapter 3
  13. Huch R and Breymann C. Anämie in Schwangerschaft und Wochenbett. UNI-MED 2005, chapt. 3, p. 35
  14. Hunt JR. High-, but not low-bioavailability diets enable substantial control of women’'s iron absorption in relation to body iron stores, with minimal adaptation within several weeks, The American Journal of Clinical Nutrition, Volume 78, Issue 6, 1 December 2003, Pages 1168–1177
  15. Hurrell R, Egli I. Iron bioavailability and dietary reference values. Am J Clin Nutr. 2010;91(5):1467S–1467S
  16. Crichton R et al. Iron Therapy – With Special Emphasis on Intravenous Administration, 4th edition, UNI-MED, 2008, chapt. 2, p. 19–20
  17. Finch CA, Bellotti V, Stray S, Lipschitz DA, Cook JD, Pippard MJ, Huebers HA. Plasma ferritin determination as a diagnostic tool. West J Med 1986;145:657–663.
  18. Douglas B. Kell and Etheresia Pretorius. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics, 2014,6, 748.
  19. T. N. Tran, S. K. Eubanks, K. J. Schaffer, C. Y. J. Zhou and M. C. Linder, Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron, Blood, 1997, 90, 4979–4986.
  20. L. A. Cohen, L. Gutierrez, A. Weiss, Y. Leichtmann- Bardoogo, D. L. Zhang, D. R. Crooks, R. Sougrat, A. Morgenstern, B. Galy, M. W. Hentze, F. J. Lazaro, T. A. Rouault and E. G. Meyron-Holtz, Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood 2010 116:1574-1584; doi: https://doi.org/10.1182/blood-2009-11-253815
  21. Cappellini MD et al. Iron deficiency across chronic inflammatory conditions: international expert opinion on definition, diagnosis, and management. Am J Hematol. 2017; 92(10):1068–1078
Functional Iron Deficiency | Ferinject CH
A functional iron deficiency exists when the total body iron stores are normal or decreased, but the iron supply to the bone marrow and other tissues is inadequate.