Anemia is seen frequently in critically ill patients and has several etiologies. This article reviews the causes with an emphasis on the effects of inflammation, examines the risks and benefits of current therapies, and discusses novel treatment options.
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;32:100-109.
2.
Vincent JL, Baron J.-F, Reinhart K., et al. Anemia and blood transfusion in critically ill patients. JAMA. 2002;288:1499-1507.
3.
Ba VN, Bota DP, Melot C., Vincent J-L.Time course of hemoglobin concentrations in nonbleeding intensive care unit patients. Crit Care Med. 2003;31:406-410.
4.
Rodriguez RM , Corwin HL, Gettinger A., Corwin MJ, Gubler D., Pearl RGNutritional deficiencies and blunted erythropoietin response as causes of the anemia of critical illness. J Crit Care. 2001;16:36-41.
5.
Weisbach V., Corbiere C., Strasser E., Zingsem J., Zimmermann R., Eckstein R.The variability of compensatory erythropoiesis in repeated autogenous blood donation. Transfusion. 2001;41:179-183.
6.
Weiss G., Goodnough LTAnemia of chronic disease. N Engl J Med. 2005 ;352:1011-1023.
7.
Wang X., Garrick MD, Yang F., Dailey LA, Piantadosi CA, Ghio AJTNF, IFN-gamma, and endotoxin increase expression of DMT1 in bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2005;289:L24-L33.
8.
Laftah AH, Sharma N., Brookes MJ, et al. Tumor necrosis factor α causes hypoferraemia and reduced intestinal iron absorption in mice. Biochem J. 2006;397:61-67.
9.
Kemma E., Pickkers P., Nemeth E., van der Hoeven H., Swinkels D.Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood. 2005;106:1864-1866.
10.
Nemeth E., Rivera S., Gabayan V., et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004;113:1271-1276.
11.
Nemeth E., Valore EV, Territo M., Schiller G., Lichtenstein A., Ganz T.Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood. 2003;101:2461-2463.
12.
Clark IA, Chaudhri G.Tumour necrosis factor may contribute to the anaemia of malaria by causing dyserythropoiesis and erythrophagocytosis. Br J Haematol . 1988; 70:99-103.
13.
Miller KL, Silverman PH, Kullgren B., Mahlmann LJTumor necrosis factor alpha and the anemia associated with murine malaria . Infect Immun. 1989;57:1542-1546.
14.
Lucchi L., Bergamini S., Iannone A., et al. Erythrocyte susceptibility to oxidative stress in chronic renal failure patients under different substitutive treatments. Artif Organs. 2005;29:67-72.
15.
Hobisch-Hagen P., Wiedermann F., Mayr A., et al. Blunted erythropoietic response to anemia in multiply traumatized patients. Crit Care Med2001;29:743-747.
16.
Rogiers P., Zhang H., Leeman M., et al. Erythropoietin response is blunted in critically ill patients . Intensive Care Med. 1997;23:159-162.
17.
Johnson JL, Moore EE, Gonzalez RJ, Fedel N., Partrick DA, Silliman CCAlteration of the postinjury hyperinflammatory response by means of resuscitation with a red cell substitute. J Trauma. 2003 ;54:133-140.
18.
Claessens Y-E. , Fontenay M., Pene F., et al. Erythropoiesis abnormalities contribute to early-onset anemia in patients with septic shock . Am J Respir Crit Care Med. 2006;174:51-57.
19.
Livingston DH, Anjaria D., Wu J., et al. Bone marrow failure following severe injury in humans. Ann Surg. 2003;238:748-753.
20.
Thawani N., Tam M., Change K.-H, Stevenson MMInterferon-γ mediates suppression of erythropoiesis but not reduced red cell survival following CpG-ODN administration in vivo. Exp Hematol. 2006;34: 1451-1461.
21.
Malone DL, Dunne J., Tracy JK, Putnam AT, Scalea TM, Napolitano LMBlood transfusion, independent of shock severity, is associated with worse outcome in trauma. J Trauma. 2003;54:898-905.
22.
Dunne JR, Malone DL, Tracy JK, Napolitano LMAllogenic blood transfusion in the first 24 hours after trauma is associated with increased systemic inflammatory response syndrome (SIRS) and death. Surg Infect (Larchmt). 2004;5:395-404.
23.
Hebert PC, Wells G., Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med. 1999;340: 490-417.
24.
Hebert PC, Blajchman MA, Cook DJ, et al. Do blood transfusions improve outcomes related to mechanical ventilation? Chest. 2001;119:1850-1857.
25.
Fransen E., Maessen J., Dentener M., Senden N., Buurman W.Impact of blood transfusions on inflammatory mediator release in patients undergoing cardiac surgery. Chest. 1999;116:1233-1239.
26.
Avall A., Hyllner M., Bengtson J., Carlsson L., Bengtsson A.Postoperative inflammatory response after autologous and allogeneic blood transfusion. Anesthesiology. 1997; 87:511-516.
27.
Moore FA, Moore EE, Sauaia A.Blood transfusion: an independent risk factor for postinjury multiple organ failure. Arch Surg. 1997;132:620-625.
28.
Silliman CC , Moore EE, Johnson JL, Gonzales RJ, Biffl WLTransfusion of the injured patient: proceed with caution. Shock. 2004;21:291-299.
29.
Nathens ABMassive transfusion as a risk factor for acute lung injury: association or causation?Crit Care Med. 2006;34(suppl):S144-S150.
30.
Weiskopf RB , Viele MK, Feiner J., et al. Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA. 1998;279:217-221.
31.
Leiberman JA , Weiskopf RB, Kelley SD, et al. Critical oxygen delivery in conscious humans is less than 7.3 ml O2· x2kg-1· x2min-1. Anesthesiology . 2000 ;92:407-413.
32.
Hopf HW, Viele M., Watson JJ, et al. Subcutaneous perfusion and oxygen during acute severe isovolemic hemodilution in healthy volunteers. Arch Surg. 2000;135: 1443-1449.
33.
Marik PE, Sibbald WJEffect of stored-blood transfusion on oxygen delivery in patients with sepsis . JAMA. 1993;269:3024-3029.
34.
Suttner S., Piper SN, Kumle B., et al. The influence of allogeneic red blood cell transfusion compared with 100% oxygen ventilation on systemic oxygen transport and skeletal muscle oxygen tension after cardiac surgery. Anesth Analg. 2004;99:2-11.
35.
Zimmerman JLUse of blood products in sepsis: an evidence-based review. Crit Care Med.2004;32(suppl): S5433-S547.
36.
Wu W-C. , Rathore SS, Wang Y., Radford MJ, Krumholz HMBlood transfusion in elderly patients with acute myocardial infarction. N Engl J Med. 2001;345:1230-1236.
37.
Rao SV, Jollis JG, Harrington RA, et al. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA. 2004;292:1555-1562.
38.
Hamasaki N. , Yamamoto M.Red blood cell function and blood storage . Vox Sang. 2000;79:191-197.
39.
Tinmouth A. , Fergussion D., Yee IC, Hebert PC . Clinical consequences of red cell storage in the critically ill. Transfusion. 2006;46:2014-2027.
40.
Gibson JG, Aub JC, Evans RD, Peacock WC, Irvine JW, Sack T.The measurement of post-transfusion survival of preserved stored human erythrocytes by means of two isotopes of radioactive iron. J Clin Invest . 1947;26:704-714.
41.
Valeri CR, Pivacek LE, Cassidy GP, Ragno G.24-hour 51Cr post-transfusion survival, 51Cr life span and haemolysis of red blood cells stored at 4°C for 56 days in AS-3. Vox Sang. 2001;80:48-50.
42.
Corwin HL, Gettinger A., Rodriguez R., et al. Efficacy of recombinant human erythropoietin in the critically ill patient: a randomized, double-blind, placebo-controlled trial. Crit Care Med. 1999;27:2346-2350.
43.
Corwin HL, Gettinger A., Pearl RG, et al. Efficacy of recombinant human erythropoietin in critically ill patients. JAMA. 2002;288:2827-2835.
44.
Corwin HLrHuEPO in critically ill patients: Epo III. Paper presented at: Society for Critical Care Medicine 36th Critical Care Congress ; February 17-21, 2007; Orlando, FL.
45.
Hasselblatt M., Ehrenreich H., Siren A.-L. The brain erythropoietin system and its potential for therapeutic exploitation in brain disease. J Neurosurg Anesthesiol. 2006;18:132-138.
46.
Bohlius J., Wilson J., Seidenfeld J., et al. Erythropoietin or darbepoetin for patients with cancer. Cochrane Database Syst Rev.2006(3):CD003407.
47.
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;355:2071-2084.
48.
FDA/CDER drug information page. Food and Drug Administration Web site. http://www.fda.gov/cder/drug/infopage/RHE/default.htm . Accessed May 8, 2007.
49.
Bellamy MC, Gedney JAUnrecognized iron deficiency in critical illness. Lancet. 1998;352:1903.
50.
Javadi P., Buchman TG, Stromberg PE, et al. High-dose exogenous iron following cecal ligation and puncture increases mortality rate in mice and is associated with an increase in gut epithelial and splenic apoptosis. Crit Care Med. 2004;32:1178-1185.
51.
Troost FJ, Saris WHM, Haenen Grmm, Bast A., Brummer R-JM.New method to study oxidative damage and antioxidants in the human small bowel: effects of iron application. Am J Physiol Gastrointest Liver Physiol. 2003;285:G354-G359.
Leung JM, Weiskopf RB, Feiner J., et al. Electrocardiographic ST-segment changes during acute, severe isovolemic hemodilution in humans. Anesthesiology. 2000; 93:1004-1010.
54.
Toy P., Feiner J., Viele MK, Watson J., Yeap H., Weiskopf RBFatigue during acute isovolemic anemia in healthy, resting humans . Transfusion. 2000;40:457-460.
55.
Weiskopf RB , Kramer JH, Viele M., et al. Acute severe isovolemic anemia impairs cognitive function and memory in humans. Anesthesiology. 2000;92:1646-1652.
56.
Shapiro MJ, Gettinger A., Corwin HL, et al. Anemia and blood transfusion in trauma patients admitted to the intensive care unit. J Trauma. 2003;55:269-274.
57.
Madjdpour C. , Spahn DR, Weiskopf RBAnemia and perioperative red blood cell transfusion: a matter of tolerance. Crit Care Med.2006 ;35(suppl):S102-S108.
58.
West MA, Shapiro MB, Nathens, AB et al. Guidelines for transfusion in the trauma patient. J Trauma. 2006;61:436-439.
59.
Carson JL, Noveck H., Berlin JA, Gould SAMortality and morbidity in patients with very low postoperative Hb levels who decline blood transfusion. Transfusion. 2002;42:812-818.
60.
Moore EE, Johnson JL, Cheng AM, Masuno T., Banerjee A.Insights from studies of blood substitutes in trauma. Shock . 2005;24:197-205.
61.
Krause A., Neitz S., Magert HJ, et al. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett. 2000;480:147-150.
