Skip to main content

Transferrin as a Possible Treatment for Anemia of Inflammation in the Critically Ill

  • Chapter
  • First Online:
Annual Update in Intensive Care and Emergency Medicine 2019

Abstract

Previously termed ‘anemia of chronic diseases’, anemia developing as a consequence of inflammation is now called anemia of inflammation. In this chapter, we describe the prevalence and etiology of anemia of inflammation. Therapeutic strategies for anemia of inflammation that are currently under development are discussed, with a special emphasis on the rationale of transferrin as a novel therapy for anemia of inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Vincent JL, Baron JF, Reinhart K, et al. Anemia and blood transfusion in critically ill patients. JAMA. 2002;288:1499–507.

    Google Scholar 

  2. Walsh TS, Lee RJ, Maciver CR, et al. Anemia during and at discharge from intensive care: the impact of restrictive blood transfusion practice. Intensive Care Med. 2006;32:100–9.

    Article  Google Scholar 

  3. Corwin HL, Gettinger A, Pearl RG, et al. The CRIT Study: anemia and blood transfusion in the critically ill—current clinical practice in the United States. Crit Care Med. 2004;32:39–52.

    Article  Google Scholar 

  4. Sihler KC, Napolitano LM. Anemia of inflammation in critically ill patients. J Intensive Care Med. 2008;23:295–302.

    Article  Google Scholar 

  5. Lasocki S, Baron G, Driss F, et al. Diagnostic accuracy of serum hepcidin for iron deficiency in critically ill patients with anemia. Intensive Care Med. 2010;36:1044–8.

    Article  CAS  Google Scholar 

  6. Prakash D. Anemia in the ICU: anemia of chronic disease versus anemia of acute illness. Crit Care Clin. 2012;28:333–43.

    Article  Google Scholar 

  7. Pieracci FM, Barie PS. Diagnosis and management of iron-related anemias in critical illness. Crit Care Med. 2006;34:1898–905.

    Article  Google Scholar 

  8. Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 2003;102:783–8.

    Article  CAS  Google Scholar 

  9. Truman-Rosentsvit M, Berenbaum D, Spektor L, et al. Ferritin is secreted via 2 distinct nonclassical vesicular pathways. Blood. 2018;131:342–52.

    Article  CAS  Google Scholar 

  10. Ritchie RF, Palomaki GE, Neveux LM, et al. Reference distributions for the negative acute-phase serum proteins, albumin, transferrin and transthyretin: a practical, simple and clinically relevant approach in a large cohort. J Clin Lab Anal. 1999;13:273–9.

    Article  CAS  Google Scholar 

  11. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352:1011–23.

    Article  CAS  Google Scholar 

  12. Holst LB, Haase N, Wetterslev J, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371:1381–91.

    Article  Google Scholar 

  13. Cassat JE, Skaar EP. Iron in infection and immunity. Cell Host Microbe. 2013;13:509–19.

    Article  CAS  Google Scholar 

  14. Hébert PC, et al. TRICC Trial—a multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med. 1999;340:409–17.

    Article  Google Scholar 

  15. Murphy GJ, Pike K, Rogers CA, et al. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med. 2015;372:997–1008.

    Article  CAS  Google Scholar 

  16. Carson JL, Terrin ML, Noveck H, et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365:2453–62.

    Article  CAS  Google Scholar 

  17. Pieracci FM, Stovall RT, Jaouen B, et al. A multicenter, randomized clinical trial of IV iron supplementation for anemia of traumatic critical illness. Crit Care Med. 2014;42:2048–57.

    Article  CAS  Google Scholar 

  18. Shah A, Roy NB, McKechnie S, et al. Iron supplementation to treat anaemia in adult critical care patients: a systematic review and meta-analysis. Crit Care. 2016;20:306.

    Article  Google Scholar 

  19. Litton E, Baker S, Erber WN, et al. Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial. Intensive Care Med. 2016;42:1715–22.

    Article  CAS  Google Scholar 

  20. Pieracci FM, Henderson P, Rodney JRM, et al. Randomized, double-blind, placebo-controlled trial of effects of enteral iron supplementation on anemia and risk of infection during surgical critical illness. Surg Infect. 2009;10:9–19.

    Article  Google Scholar 

  21. Garrido-Martín P, Nassar-Mansur MI, de la Llana-Ducrós R, et al. The effect of intravenous and oral iron administration on perioperative anaemia and transfusion requirements in patients undergoing elective cardiac surgery: a randomized clinical trial. Interact Cardiovasc Thorac Surg. 2012;15:1013–8.

    Article  Google Scholar 

  22. Madi-Jebara SN, Sleilaty GS, Achouh PE, et al. Postoperative intravenous iron used alone or in combination with low-dose erythropoietin is not effective for correction of anemia after cardiac surgery. J Cardiothorac Vasc Anesth. 2004;18:59–63.

    Article  CAS  Google Scholar 

  23. Rohde JM, Dimcheff DE, Blumberg N, et al. Health care-associated infection after red blood cell transfusion: a systematic review and meta-analysis. JAMA. 2014;311:1317–26.

    Article  CAS  Google Scholar 

  24. Corwin HL, Gettinger A, Pearl RG, et al. Efficacy of recombinant human erythropoietin in critically ill patients a randomized controlled trial. JAMA. 2002;288:2827–35.

    Article  CAS  Google Scholar 

  25. Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355:333–40.

    Article  Google Scholar 

  26. Tonia T, Mettler A, Robert N, et al. Erythropoietin or darbepoetin for patients with cancer. Cochrane Database Syst Rev. 2012;2012:CD003407.

    Google Scholar 

  27. Marik PE, Corwin HL. Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature. Crit Care Med. 2008;36:2667–74.

    Article  Google Scholar 

  28. Schipperus M, Rijnbeek B, Reddy M, et al. CNTO328 (Anti-IL-6 mAb) Treatment is associated with an increase in hemoglobin (Hb) and decrease in hepcidin levels in renal cell carcinoma (RCC). Blood. 2009;114:1551 (abst).

    Google Scholar 

  29. Song S-NJ, Iwahashi M, Tomosugi N, et al. Comparative evaluation of the effects of treatment with tocilizumab and TNF-a inhibitors on serum hepcidin, anemia response and disease activity in rheumatoid arthritis patients. Arthritis Res Ther. 2013;15:1.

    CAS  Google Scholar 

  30. Song SNJ, Tomosugi N, Kawabata H, et al. Down-regulation of hepcidin resulting from long-term treatment with an anti-IL-6 receptor antibody (tocilizumab) improves anemia of inflammation in multicentric Castleman disease. Blood. 2010;116:3627–34.

    Article  CAS  Google Scholar 

  31. Isaacs JD, Harari O, Kobold U, et al. Effect of tocilizumab on haematological markers implicates interleukin-6 signalling in the anaemia of rheumatoid arthritis. Arthritis Res Ther. 2013;15:R204.

    Article  Google Scholar 

  32. Schwoebel F, van Eijk LT, Zboralski D, et al. The effects of the anti-hepcidin Spiegelmer NOX-H94 on inflammation-induced anemia in cynomolgus monkeys. Blood. 2013;121:2311–5.

    Article  CAS  Google Scholar 

  33. Van Eijk LT, John ASE, Schwoebel F, et al. Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans. Blood. 2014;124:2643–6.

    Article  Google Scholar 

  34. Sasu BJ, Cooke KS, Arvedson TL, et al. Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia. Blood. 2010;115:3616–24.

    Article  CAS  Google Scholar 

  35. Poli M, Girelli D, Campostrini N, et al. Heparin: a potent inhibitor of hepcidin expression in vitro and in vivo Heparin: a potent inhibitor of hepcidin expression in vitro and in vivo. Blood. 2010;117:997–1004.

    Article  Google Scholar 

  36. Steinbicker AU, Sachidanandan C, Vonner AJ, et al. Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation. Blood. 2011;117:4915–24.

    Article  CAS  Google Scholar 

  37. Chung MCM. Stucture and function of transferrin. Biochem Educ. 1984;12:146–54.

    Article  CAS  Google Scholar 

  38. Crichton RR, Charloteaux-wauters M. Iron transport and storage. Eur J Biochem. 1987;164:485–506.

    Article  CAS  Google Scholar 

  39. Parkkinen J, von Bonsdorff L, Ebeling F, Sahlstedt L. Function and therapeutic development of apotransferrin. Vox Sang. 2002;83(Suppl 1):321–6.

    Article  CAS  Google Scholar 

  40. Prakash M. Role of non-transferrin-bound iron in chornic renal failure and other disease conditions. Ren Physiol. 2007;17:188–93.

    Google Scholar 

  41. von Bonsdorff L, Tölö H, Lindeberg E, et al. Development of a pharmaceutical apotransferrin product for iron binding therapy. Biologicals. 2001;29:27–37.

    Article  Google Scholar 

  42. Hayashi A, Wada Y, Suzuki T, Shimizu A. Studies on familial hypotransferrinemia: unique clinical course and molecular pathology. Am J Hum Genet. 1993;53:201–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Boshuizen M, van der Ploeg K, von Bonsdorff L, et al. Therapeutic use of transferrin to modulate anemia and conditions of iron toxicity. Blood Rev. 2017;31:400–5.

    Article  CAS  Google Scholar 

  44. Li Bassi G, Rigol M, Marti JD, et al. A novel porcine model of ventilator-associated pneumonia caused by oropharyngeal challenge with Pseudomonas aeruginosa. Anesthesiology. 2014;120:1205–15.

    Article  Google Scholar 

  45. Sibila O, Agustí C, Torres A, et al. Experimental Pseudomonas aeruginosa pneumonia: evaluation of the associated inflammatory response. Eur Respir J. 2007;30:1167–72.

    Article  CAS  Google Scholar 

  46. Luna CM, Baquero S, Gando S, et al. Experimental severe Pseudomonas aeruginosa pneumonia and antibiotic therapy in piglets receiving mechanical ventilation. Chest. 2007;132:523–31.

    Article  Google Scholar 

  47. Hod EA, Zhang N, Sokol SA, et al. Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation. Blood. 2015;115:4284–93.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Boshuizen .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Boshuizen, M., Li Bassi, G., Juffermans, N.P. (2019). Transferrin as a Possible Treatment for Anemia of Inflammation in the Critically Ill. In: Vincent, JL. (eds) Annual Update in Intensive Care and Emergency Medicine 2019. Annual Update in Intensive Care and Emergency Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-06067-1_45

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-06067-1_45

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-06066-4

  • Online ISBN: 978-3-030-06067-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics