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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Vincent JL, Baron JF, Reinhart K, et al. Anemia and blood transfusion in critically ill patients. JAMA. 2002;288:1499–507.
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.
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.
Sihler KC, Napolitano LM. Anemia of inflammation in critically ill patients. J Intensive Care Med. 2008;23:295–302.
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.
Prakash D. Anemia in the ICU: anemia of chronic disease versus anemia of acute illness. Crit Care Clin. 2012;28:333–43.
Pieracci FM, Barie PS. Diagnosis and management of iron-related anemias in critical illness. Crit Care Med. 2006;34:1898–905.
Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 2003;102:783–8.
Truman-Rosentsvit M, Berenbaum D, Spektor L, et al. Ferritin is secreted via 2 distinct nonclassical vesicular pathways. Blood. 2018;131:342–52.
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.
Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352:1011–23.
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.
Cassat JE, Skaar EP. Iron in infection and immunity. Cell Host Microbe. 2013;13:509–19.
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.
Murphy GJ, Pike K, Rogers CA, et al. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med. 2015;372:997–1008.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Tonia T, Mettler A, Robert N, et al. Erythropoietin or darbepoetin for patients with cancer. Cochrane Database Syst Rev. 2012;2012:CD003407.
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.
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).
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.
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.
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.
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.
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.
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.
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.
Steinbicker AU, Sachidanandan C, Vonner AJ, et al. Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation. Blood. 2011;117:4915–24.
Chung MCM. Stucture and function of transferrin. Biochem Educ. 1984;12:146–54.
Crichton RR, Charloteaux-wauters M. Iron transport and storage. Eur J Biochem. 1987;164:485–506.
Parkkinen J, von Bonsdorff L, Ebeling F, Sahlstedt L. Function and therapeutic development of apotransferrin. Vox Sang. 2002;83(Suppl 1):321–6.
Prakash M. Role of non-transferrin-bound iron in chornic renal failure and other disease conditions. Ren Physiol. 2007;17:188–93.
von Bonsdorff L, Tölö H, Lindeberg E, et al. Development of a pharmaceutical apotransferrin product for iron binding therapy. Biologicals. 2001;29:27–37.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
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)