Anemia in the Surgical ICU

  • Aryeh Shander
  • Lena M. Napolitano
  • Margit Kaufman


Anemia is common in critically ill and it is associated with worsening of outcomes and increased risk of transfusion. Various compensatory mechanisms are activated to mitigate the negative effects of reduced oxygen-carrying capacity of blood in anemia, but these adaptations have limits and as the limits are reached, tissue oxygen delivery will no longer be adequate to meet the demand and ischemia and tissue injury may occur. Anemia is often multifactorial and in critically ill patients, it can be caused by blood loss, impaired erythropoiesis, and reduced life span of red blood cells, iron deficiency (absolute or functional), and hemodilution. Various management strategies are available to address these etiologies. Given the risks of transfusion, allogeneic blood should be used judiciously and only when clearly indicated and alongside other management and preventive strategies to reduce unnecessary and avoidable transfusions.


Anemia Hemoglobin Ischemia Transfusion Iron Erythropoietin 


  1. 1.
    Napolitano LM. Scope of the problem: epidemiology of anemia and use of blood transfusions in critical care. Crit Care. 2004;8 Suppl 2:S1–8.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Shander A, Goodnough LT, Javidroozi M, Auerbach M, Carson J, Ershler WB, et al. Iron deficiency anemia – bridging the knowledge and practice gap. Transfus Med Rev. 2014;28(3):156–66.PubMedCrossRefGoogle Scholar
  3. 3.
    Blanc B, Finch CA, Hallberg L. Nutritional aneamias. Report of a WHO Scientific Group. WHO Tech Rep Ser. 1968;405:1–40.Google Scholar
  4. 4.
    The global prevalence of anaemia in 2011. Geneva: World Health Organization; 2015.Google Scholar
  5. 5.
    Skjelbakken T, Langbakk B, Dahl IM, Lochen ML. Haemoglobin and anaemia in a gender perspective: the Tromso study. Eur J Haematol. 2005;74(5):381–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood. 2006;107(5):1747–50.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Guralnik JM, et al. Anemia in the elderly: a public health crisis in hematology. ASH Education Program Book. 2005;1(2005):528–32.CrossRefGoogle Scholar
  8. 8.
    Corwin HL, Gettinger A, Pearl RG, Fink MP, Levy MM, Abraham E, 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(1):39–52.PubMedCrossRefGoogle Scholar
  9. 9.
    Corwin HL. Anemia and red blood cell transfusion in the critically ill. Semin Dial. 2006;19(6):513–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Nguyen BV, Bota DP, Melot C, Vincent JL. Time course of hemoglobin concentrations in nonbleeding intensive care unit patients. Crit Care Med. 2003;31(2):406–10.PubMedCrossRefGoogle Scholar
  11. 11.
    Shander A. Anemia in the critically ill. Crit Care Clin. 2004;20(2):159–78.PubMedCrossRefGoogle Scholar
  12. 12.
    Thomas J, Jensen L, Nahirniak S, Gibney RT. Anemia and blood transfusion practices in the critically ill: a prospective cohort review. Heart Lung. 2010;39(3):217–25.PubMedCrossRefGoogle Scholar
  13. 13.
    Vincent JL, Baron JF, Reinhart K, Gattinoni L, Thijs L, Webb A, et al. Anemia and blood transfusion in critically ill patients. JAMA. 2002;288(12):1499–507.PubMedCrossRefGoogle Scholar
  14. 14.
    Walsh TS, Lee RJ, Maciver CR, Garrioch M, Mackirdy F, Binning AR, et al. Anemia during and at discharge from intensive care: the impact of restrictive blood transfusion practice. Intensive Care Med. 2006;32(1):100–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Walsh TS, Garrioch M, Maciver C, Lee RJ, Mackirdy F, McClelland DB, et al. Red cell requirements for intensive care units adhering to evidence-based transfusion guidelines. Transfusion. 2004;44(10):1405–11.PubMedCrossRefGoogle Scholar
  16. 16.
    Chant C, Wilson G, Friedrich JO. Anemia, transfusion, and phlebotomy practices in critically ill patients with prolonged ICU length of stay: a cohort study. Crit Care. 2006;10(5):R140.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Shapiro MJ, Gettinger A, Corwin HL, Napolitano L, Levy M, Abraham E, et al. Anemia and blood transfusion in trauma patients admitted to the intensive care unit. J Trauma. 2003;55(2):269–73.PubMedCrossRefGoogle Scholar
  18. 18.
    Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340(6):409–17.CrossRefPubMedGoogle Scholar
  19. 19.
    Palmieri TL, Caruso DM, Foster KN, Cairns BA, Peck MD, Gamelli RL, et al. Effect of blood transfusion on outcome after major burn injury: a multicenter study. Crit Care Med. 2006;34(6):1602–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Rao MP, Boralessa H, Morgan C, Soni N, Goldhill DR, Brett SJ, et al. Blood component use in critically ill patients. Anaesthesia. 2002;57(6):530–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Vincent JL, Sakr Y, Sprung C, Harboe S, Damas P. Are blood transfusions associated with greater mortality rates? Results of the sepsis occurrence in acutely ill patients study. Anesthesiology. 2008;108(1):31–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Walsh TS, McClelland DB, Lee RJ, Garrioch M, Maciver CR, McArdle F, et al. Prevalence of ischaemic heart disease at admission to intensive care and its influence on red cell transfusion thresholds: multicentre Scottish study. Br J Anaesth. 2005;94(4):445–52.PubMedCrossRefGoogle Scholar
  23. 23.
    Zilberberg MD, Stern LS, Wiederkehr DP, Doyle JJ, Shorr AF. Anemia, transfusions and hospital outcomes among critically ill patients on prolonged acute mechanical ventilation: a retrospective cohort study. Crit Care. 2008;12(2):R60.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Dasta J, Mody SH, McLaughlin T, Leblanc J, Shen Y, Genetti M, et al. Current management of anemia in critically ill patients: analysis of a database of 139 hospitals. Am J Ther. 2008;15(5):423–30.PubMedCrossRefGoogle Scholar
  25. 25.
    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(9):2667–74.PubMedCrossRefGoogle Scholar
  26. 26.
    Baskurt OK, Yalcin O, Meiselman HJ. Hemorheology and vascular control mechanisms. Clin Hemorheol Microcirc. 2004;30(3–4):169–78.PubMedGoogle Scholar
  27. 27.
    Shander A, Javidroozi M, Ozawa S, Hare GM. What is really dangerous: anaemia or transfusion? Br J Anaesth. 2011;107 Suppl 1:i41–59.PubMedCrossRefGoogle Scholar
  28. 28.
    Otto JM, Montgomery HE, Richards T. Haemoglobin concentration and mass as determinants of exercise performance and of surgical outcome. Extrem Physiol Med. 2013;2(1):33.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    McLellan SA, Walsh TS. Oxygen delivery and haemoglobin. Educ Anaesth Crit Care Pain. 2004;4(4):123–6.CrossRefGoogle Scholar
  30. 30.
    Madjdpour C, Spahn DR, Weiskopf RB. Anemia and perioperative red blood cell transfusion: a matter of tolerance. Crit Care Med. 2006;34(5 Suppl):S102–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Lane P, Gross S. Hemoglobin as a chariot for NO bioactivity. Nat Med. 2002;8(7):657–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Hamilton C, Steinlechner B, Gruber E, Simon P, Wollenek G. The oxygen dissociation curve: quantifying the shift. Perfusion. 2004;19(3):141–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Wilson DF, Lee WM, Makonnen S, Finikova O, Apreleva S, Vinogradov SA. Oxygen pressures in the interstitial space and their relationship to those in the blood plasma in resting skeletal muscle. J Appl Physiol. 2006;101(6):1648–56.PubMedCrossRefGoogle Scholar
  34. 34.
    Lecoq J, Parpaleix A, Roussakis E, Ducros M, Houssen YG, Vinogradov SA, et al. Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels. Nat Med. 2011;17(7):893–8.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Sakadzic S, Roussakis E, Yaseen MA, Mandeville ET, Srinivasan VJ, Arai K, et al. Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue. Nat Methods. 2010;7(9):755–9.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Sharan M, Vovenko EP, Vadapalli A, Popel AS, Pittman RN. Experimental and theoretical studies of oxygen gradients in rat pial microvessels. J Cereb Blood Flow Metab. 2008;28(9):1597–604.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Baieth HE. Physical parameters of blood as a non-Newtonian fluid. Int J Biomed Sci. 2008;4(4):323–9.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Lucker A, Weber B, Jenny P. A dynamic model of oxygen transport from capillaries to tissue with moving red blood cells. Am J Physiol Heart Circ Physiol. 2015;308(3):H206–16.PubMedCrossRefGoogle Scholar
  39. 39.
    Taylor CT. Mitochondria and cellular oxygen sensing in the HIF pathway. Biochem J. 2008;409(1):19–26.PubMedCrossRefGoogle Scholar
  40. 40.
    Spinelli E, Bartlett RH. Anemia and transfusion in critical care: physiology and management. J Intensive Care Med. 2015.Google Scholar
  41. 41.
    Hayden SJ, Albert TJ, Watkins TR, Swenson ER. Anemia in critical illness: insights into etiology, consequences, and management. Am J Respir Crit Care Med. 2012;185(10):1049–57.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Stamati K, Mudera V, Cheema U. Evolution of oxygen utilization in multicellular organisms and implications for cell signalling in tissue engineering. J Tissue Eng. 2011;2(1):2041731411432365.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Kurata M, Suzuki M, Agar NS. Antioxidant systems and erythrocyte life-span in mammals. Comp Biochem Physiol B. 1993;106(3):477–87.PubMedCrossRefGoogle Scholar
  44. 44.
    Mohanty JG, Nagababu E, Rifkind JM. Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging. Front Physiol. 2014;5:84.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Malka R, Delgado FF, Manalis SR, Higgins JM. In vivo volume and hemoglobin dynamics of human red blood cells. PLoS Comput Biol. 2014;10(10):e1003839.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Piomelli S, Seaman C. Mechanism of red blood cell aging: relationship of cell density and cell age. Am J Hematol. 1993;42(1):46–52.PubMedCrossRefGoogle Scholar
  47. 47.
    Sugawara Y, Hayashi Y, Shigemasa Y, Abe Y, Ohgushi I, Ueno E, et al. Molecular biosensing mechanisms in the spleen for the removal of aged and damaged red cells from the blood circulation. Sensors (Basel). 2010;10(8):7099–121.CrossRefGoogle Scholar
  48. 48.
    Lang F, Lang E, Foller M. Physiology and pathophysiology of eryptosis. Transfus Med Hemother. 2012;39(5):308–14.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Fadeel B, Xue D, Kagan V. Programmed cell clearance: molecular regulation of the elimination of apoptotic cell corpses and its role in the resolution of inflammation. Biochem Biophys Res Commun. 2010;396(1):7–10.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Rice L, Alfrey CP. The negative regulation of red cell mass by neocytolysis: physiologic and pathophysiologic manifestations. Cell Physiol Biochem. 2005;15(6):245–50.PubMedCrossRefGoogle Scholar
  51. 51.
    Koulnis M, Porpiglia E, Hidalgo D, Socolovsky M. Erythropoiesis: from molecular pathways to system properties. Adv Exp Med Biol. 2014;844:37–58.PubMedCrossRefGoogle Scholar
  52. 52.
    Ogunshola OO, Bogdanova AY. Epo and non-hematopoietic cells: what do we know? Methods Mol Biol. 2013;982:13–41.PubMedCrossRefGoogle Scholar
  53. 53.
    Chapler CK, Cain SM. The physiologic reserve in oxygen carrying capacity: studies in experimental hemodilution. Can J Physiol Pharmacol. 1986;64(1):7–12.PubMedCrossRefGoogle Scholar
  54. 54.
    Greer SN, Metcalf JL, Wang Y, Ohh M. The updated biology of hypoxia-inducible factor. EMBO J. 2012;31(11):2448–60.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Halperin ML, Cheema-Dhadli S, Lin SH, Kamel KS. Properties permitting the renal cortex to be the oxygen sensor for the release of erythropoietin: clinical implications. Clin J Am Soc Nephrol. 2006;1(5):1049–53.PubMedCrossRefGoogle Scholar
  56. 56.
    Milsom WK, Burleson ML. Peripheral arterial chemoreceptors and the evolution of the carotid body. Respir Physiol Neurobiol. 2007;157(1):4–11.PubMedCrossRefGoogle Scholar
  57. 57.
    Evans RG, Ince C, Joles JA, Smith DW, May CN, O’Connor PM, et al. Haemodynamic influences on kidney oxygenation: clinical implications of integrative physiology. Clin Exp Pharmacol Physiol. 2013;40(2):106–22.PubMedCrossRefGoogle Scholar
  58. 58.
    Johannes T, Mik EG, Nohe B, Unertl KE, Ince C. Acute decrease in renal microvascular PO2 during acute normovolemic hemodilution. Am J Physiol Renal Physiol. 2007;292(2):F796–803.PubMedCrossRefGoogle Scholar
  59. 59.
    Deem S, Hedges RG, McKinney S, Polissar NL, Alberts MK, Swenson ER. Mechanisms of improvement in pulmonary gas exchange during isovolemic hemodilution. J Appl Physiol (1985). 1999;87(1):132–41.CrossRefGoogle Scholar
  60. 60.
    Metivier F, Marchais SJ, Guerin AP, Pannier B, London GM. Pathophysiology of anaemia: focus on the heart and blood vessels. Nephrol Dial Transplant. 2000;15 Suppl 3:14–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Cabrales P, Martini J, Intaglietta M, Tsai AG. Blood viscosity maintains microvascular conditions during normovolemic anemia independent of blood oxygen-carrying capacity. Am J Physiol Heart Circ Physiol. 2006;291(2):H581–90.PubMedCrossRefGoogle Scholar
  62. 62.
    Li M, Bertout JA, Ratcliffe SJ, Eckenhoff MF, Simon MC, Floyd TF. Acute anemia elicits cognitive dysfunction and evidence of cerebral cellular hypoxia in older rats with systemic hypertension. Anesthesiology. 2010;113(4):845–58.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    McLaren AT, Mazer CD, Zhang H, Liu E, Mok L, Hare GM. A potential role for inducible nitric oxide synthase in the cerebral response to acute hemodilution. Can J Anaesth. 2009;56(7):502–9.PubMedCrossRefGoogle Scholar
  64. 64.
    El Hasnaoui-Saadani R, Pichon A, Marchant D, Olivier P, Launay T, Quidu P, et al. Cerebral adaptations to chronic anemia in a model of erythropoietin-deficient mice exposed to hypoxia. Am J Physiol Regul Integr Comp Physiol. 2009;296(3):R801–11.PubMedCrossRefGoogle Scholar
  65. 65.
    Wolff CB. Normal cardiac output, oxygen delivery and oxygen extraction. Adv Exp Med Biol. 2007;599:169–82.PubMedCrossRefGoogle Scholar
  66. 66.
    Weiskopf RB, Viele MK, Feiner J, Kelley S, Lieberman J, Noorani M, et al. Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA. 1998;279(3):217–21.PubMedCrossRefGoogle Scholar
  67. 67.
    van Bommel J, Trouwborst A, Schwarte L, Siegemund M, Ince C, Henny C. Intestinal and cerebral oxygenation during severe isovolemic hemodilution and subsequent hyperoxic ventilation in a pig model. Anesthesiology. 2002;97(3):660–70.PubMedCrossRefGoogle Scholar
  68. 68.
    Kaelin Jr WG, Ratcliffe PJ. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell. 2008;30(4):393–402.PubMedCrossRefGoogle Scholar
  69. 69.
    Semenza GL. Hypoxia-inducible factor 1 (HIF-1) pathway. Sci STKE. 2007;2007(407):cm8.PubMedCrossRefGoogle Scholar
  70. 70.
    Semenza GL. O2-regulated gene expression: transcriptional control of cardiorespiratory physiology by HIF-1. J Appl Physiol (1985). 2004;96(3):1173–7.CrossRefGoogle Scholar
  71. 71.
    Gruber M, Hu CJ, Johnson RS, Brown EJ, Keith B, Simon MC. Acute postnatal ablation of Hif-2alpha results in anemia. Proc Natl Acad Sci U S A. 2007;104(7):2301–6.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Kim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3(3):177–85.PubMedCrossRefGoogle Scholar
  73. 73.
    Matsuoka T, Saiki C, Mortola JP. Metabolic and ventilatory responses to anemic hypoxia in conscious rats. J Appl Physiol (1985). 1994;77(3):1067–72.CrossRefGoogle Scholar
  74. 74.
    Corwin HL, Krantz SB. Anemia of the critically ill: “acute” anemia of chronic disease. Crit Care Med. 2000;28(8):3098–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Zarychanski R, Houston DS. Anemia of chronic disease: a harmful disorder or an adaptive, beneficial response? CMAJ. 2008;179(4):333–7.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Sihler KC, Napolitano LM. Anemia of inflammation in critically ill patients. J Intensive Care Med. 2008;23(5):295–302.PubMedCrossRefGoogle Scholar
  77. 77.
    von Ahsen N, Muller C, Serke S, Frei U, Eckardt KU. Important role of nondiagnostic blood loss and blunted erythropoietic response in the anemia of medical intensive care patients. Crit Care Med. 1999;27(12):2630–9.CrossRefGoogle Scholar
  78. 78.
    MacIsaac CM, Presneill JJ, Boyce CA, Byron KL, Cade JF. The influence of a blood conserving device on anaemia in intensive care patients. Anaesth Intensive Care. 2003;31(6):653–7.PubMedGoogle Scholar
  79. 79.
    Mukhopadhyay A, Yip HS, Prabhuswamy D, Chan YH, Phua J, Lim TK, et al. The use of a blood conservation device to reduce red blood cell transfusion requirements: a before and after study. Crit Care. 2010;14(1):R7.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Page C, Retter A, Wyncoll D. Blood conservation devices in critical care: a narrative review. Ann Intensive Care. 2013;3:14.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Peruzzi WT, Parker MA, Lichtenthal PR, Cochran-Zull C, Toth B, Blake M. A clinical evaluation of a blood conservation device in medical intensive care unit patients. Crit Care Med. 1993;21(4):501–6.PubMedCrossRefGoogle Scholar
  82. 82.
    Smoller BR, Kruskall MS, Horowitz GL. Reducing adult phlebotomy blood loss with the use of pediatric-sized blood collection tubes. Am J Clin Pathol. 1989;91(6):701–3.PubMedCrossRefGoogle Scholar
  83. 83.
    Dolman HS, Evans K, Zimmerman LH, Lavery T, Baylor AE, Wilson RF, et al. Impact of minimizing diagnostic blood loss in the critically ill. Surgery. 2015;158(4):1083–7.PubMedCrossRefGoogle Scholar
  84. 84.
    Krafte-Jacobs B, Levetown ML, Bray GL, Ruttimann UE, Pollack MM. Erythropoietin response to critical illness. Crit Care Med. 1994;22(5):821–6.PubMedCrossRefGoogle Scholar
  85. 85.
    Krafte-Jacobs B. Anemia of critical illness and erythropoietin deficiency. Intensive Care Med. 1997;23(2):137–8.PubMedCrossRefGoogle Scholar
  86. 86.
    Rodriguez RM, Corwin HL, Gettinger A, Corwin MJ, Gubler D, Pearl RG. Nutritional deficiencies and blunted erythropoietin response as causes of the anemia of critical illness. J Crit Care. 2001;16(1):36–41.PubMedCrossRefGoogle Scholar
  87. 87.
    Rogiers P, Zhang H, Leeman M, Nagler J, Neels H, Melot C, et al. Erythropoietin response is blunted in critically ill patients. Intensive Care Med. 1997;23(2):159–62.PubMedCrossRefGoogle Scholar
  88. 88.
    van Iperen CE, Gaillard CA, Kraaijenhagen RJ, Braam BG, Marx JJ, van de Wiel A. Response of erythropoiesis and iron metabolism to recombinant human erythropoietin in intensive care unit patients. Crit Care Med. 2000;28(8):2773–8.PubMedCrossRefGoogle Scholar
  89. 89.
    DeAngelo AJ, Bell DG, Quinn MW, Long DE, Ouellette DR. Erythropoietin response in critically ill mechanically ventilated patients: a prospective observational study. Crit Care. 2005;9(3):R172–6.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Hobisch-Hagen P, Wiedermann F, Mayr A, Fries D, Jelkmann W, Fuchs D, et al. Blunted erythropoietic response to anemia in multiply traumatized patients. Crit Care Med. 2001;29(4):743–7.PubMedCrossRefGoogle Scholar
  91. 91.
    Fonseca RB, Mohr AM, Wang L, Sifri ZC, Rameshwar P, Livingston DH. The impact of a hypercatecholamine state on erythropoiesis following severe injury and the role of IL-6. J Trauma. 2005;59(4):884–9.PubMedCrossRefGoogle Scholar
  92. 92.
    Corwin HL, Gettinger A, Fabian TC, May A, Pearl RG, Heard S, et al. Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med. 2007;357(10):965–76.PubMedCrossRefGoogle Scholar
  93. 93.
    Turaga KK, Sugimoto JT, Forse RA. A meta-analysis of randomized controlled trials in critically ill patients to evaluate the dose-response effect of erythropoietin. J Intensive Care Med. 2007;22(5):270–82.PubMedCrossRefGoogle Scholar
  94. 94.
    Corwin HL, Gettinger A, Pearl RG, Fink MP, Levy MM, Shapiro MJ, et al. Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial. JAMA. 2002;288(22):2827–35.PubMedCrossRefGoogle Scholar
  95. 95.
    Napolitano LM, Fabian TC, Kelly KM, Bailey JA, Block EF, Langholff W, et al. Improved survival of critically ill trauma patients treated with recombinant human erythropoietin. J Trauma. 2008;65(2):285–97.PubMedCrossRefGoogle Scholar
  96. 96.
    Piagnerelli M, Cotton F, Herpain A, Rapotec A, Chatti R, Gulbis B, et al. Time course of iron metabolism in critically ill patients. Acta Clin Belg. 2013;68(1):22–7.PubMedCrossRefGoogle Scholar
  97. 97.
    Thomas DW, Hinchliffe RF, Briggs C, Macdougall IC, Littlewood T, Cavill I. Guideline for the laboratory diagnosis of functional iron deficiency. Br J Haematol. 2013;161(5):639–48.PubMedCrossRefGoogle Scholar
  98. 98.
    Fleming RE, Bacon BR. Orchestration of iron homeostasis. N Engl J Med. 2005;352(17):1741–4.PubMedCrossRefGoogle Scholar
  99. 99.
    Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011–23.PubMedCrossRefGoogle Scholar
  100. 100.
    Gangat N, Wolanskyj AP. Anemia of chronic disease. Semin Hematol. 2013;50(3):232–8.PubMedCrossRefGoogle Scholar
  101. 101.
    Ganz T. Hepcidin and iron regulation, 10 years later. Blood. 2011;117(17):4425–33.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Sihler KC, Raghavendran K, Westerman M, Ye W, Napolitano LM. Hepcidin in trauma: linking injury, inflammation, and anemia. J Trauma. 2010;69(4):831–7.PubMedCrossRefGoogle Scholar
  103. 103.
    Sasaki Y, Noguchi-Sasaki M, Yasuno H, Yorozu K, Shimonaka Y. Erythropoietin stimulation decreases hepcidin expression through hematopoietic activity on bone marrow cells in mice. Int J Hematol. 2012;96(6):692–700.PubMedCrossRefGoogle Scholar
  104. 104.
    De Domenico I, Zhang TY, Koening CL, Branch RW, London N, Lo E, et al. Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice. J Clin Invest. 2010;120(7):2395–405.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Maliken BD, Nelson JE, Kowdley KV. The hepcidin circuits act: balancing iron and inflammation. Hepatology. 2011;53(5):1764–6.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Ganz T, Nemeth E. The hepcidin-ferroportin system as a therapeutic target in anemias and iron overload disorders. Hematol Am Soc Hematol Educ Prog. 2011;2011:538–42.Google Scholar
  107. 107.
    Sun CC, Vaja V, Babitt JL, Lin HY. Targeting the hepcidin-ferroportin axis to develop new treatment strategies for anemia of chronic disease and anemia of inflammation. Am J Hematol. 2012;87(4):392–400.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Ashby DR, Gale DP, Busbridge M, Murphy KG, Duncan ND, Cairns TD, et al. Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin. Haematologica. 2010;95(3):505–8.PubMedCrossRefGoogle Scholar
  109. 109.
    Elliott J, Mishler D, Agarwal R. Hyporesponsiveness to erythropoietin: causes and management. Adv Chronic Kidney Dis. 2009;16(2):94–100.PubMedCrossRefGoogle Scholar
  110. 110.
    Fung E, Nemeth E. Manipulation of the hepcidin pathway for therapeutic purposes. Haematologica. 2013;98(11):1667–76.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Schwoebel F, van Eijk LT, Zboralski D, Sell S, Buchner K, Maasch C, et al. The effects of the anti-hepcidin Spiegelmer NOX-H94 on inflammation-induced anemia in cynomolgus monkeys. Blood. 2013;121(12):2311–5.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet. 2014;46(7):678–84.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Corwin HL, Parsonnet KC, Gettinger A. RBC transfusion in the ICU. Is there a reason? Chest. 1995;108(3):767–71.PubMedCrossRefGoogle Scholar
  114. 114.
    McEvoy MT, Shander A. Anemia, bleeding, and blood transfusion in the intensive care unit: causes, risks, costs, and new strategies. Am J Crit Care. 2013;22(6 Suppl):eS1–13.PubMedCrossRefGoogle Scholar
  115. 115.
    So-Osman C, Nelissen RG, Koopman-van Gemert AW, Kluyver E, Poll RG, Onstenk R, et al. Patient blood management in elective total hip- and knee-replacement surgery (part 2): a randomized controlled trial on blood salvage as transfusion alternative using a restrictive transfusion policy in patients with a preoperative hemoglobin above 13 g/dl. Anesthesiology. 2014;120(4):852–60.PubMedCrossRefGoogle Scholar
  116. 116.
    Garratty G. Immune hemolytic anemia caused by drugs. Expert Opin Drug Saf. 2012;11(4):635–42.PubMedCrossRefGoogle Scholar
  117. 117.
    Shander A, Javidroozi M, Ashton ME. Drug-induced anemia and other red cell disorders: a guide in the age of polypharmacy. Curr Clin Pharmacol. 2011;6(4):295–303.PubMedCrossRefGoogle Scholar
  118. 118.
    Michel M. Classification and therapeutic approaches in autoimmune hemolytic anemia: an update. Expert Rev Hematol. 2011;4(6):607–18.PubMedCrossRefGoogle Scholar
  119. 119.
    Arnold DM, Donahoe L, Clarke FJ, Tkaczyk AJ, Heels-Ansdell D, Zytaruk N, et al. Bleeding during critical illness: a prospective cohort study using a new measurement tool. Clin Invest Med. 2007;30(2):E93–102.PubMedCrossRefGoogle Scholar
  120. 120.
    Drews RE. Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients. Clin Chest Med. 2003;24(4):607–22.PubMedCrossRefGoogle Scholar
  121. 121.
    Greinacher A, Selleng K. Thrombocytopenia in the intensive care unit patient. Hematol Am Soc Hematol Educ Prog. 2010;2010:135–43.Google Scholar
  122. 122.
    Corwin HL, Gettinger A, Rodriguez RM, Pearl RG, Gubler KD, Enny C, et al. Efficacy of recombinant human erythropoietin in the critically ill patient: a randomized, double-blind, placebo-controlled trial. Crit Care Med. 1999;27(11):2346–50.PubMedCrossRefGoogle Scholar
  123. 123.
    Napolitano LM. Epoetin alfa in the critically ill: what dose? Which route? Crit Care Med. 2009;37(4):1501–3.PubMedCrossRefGoogle Scholar
  124. 124.
    Swoboda SM, Lipsett PA. Intravenous iron as a risk factor for bacteremia in the surgical intensive care unit patient. Surg Infect. 2005;6:158.Google Scholar
  125. 125.
    Torres S, Kuo YH, Morris K, Neibart R, Holtz JB, Davis JM. Intravenous iron following cardiac surgery does not increase the infection rate. Surg Infect (Larchmt). 2006;7(4):361–6.CrossRefGoogle Scholar
  126. 126.
    Conrad SA, Dietrich KA, Hebert CA, Romero MD. Effect of red cell transfusion on oxygen consumption following fluid resuscitation in septic shock. Circ Shock. 1990;31(4):419–29.PubMedGoogle Scholar
  127. 127.
    Marik PE, Sibbald WJ. Effect of stored-blood transfusion on oxygen delivery in patients with sepsis. JAMA. 1993;269(23):3024–9.PubMedCrossRefGoogle Scholar
  128. 128.
    Ronco JJ, Phang PT, Walley KR, Wiggs B, Fenwick JC, Russell JA. Oxygen consumption is independent of changes in oxygen delivery in severe adult respiratory distress syndrome. Am Rev Respir Dis. 1991;143(6):1267–73.PubMedCrossRefGoogle Scholar
  129. 129.
    Shah DM, Gottlieb ME, Rahm RL, Stratton HH, Barie PS, Paloski WH, et al. Failure of red blood cell transfusion to increase oxygen transport or mixed venous PO2 in injured patients. J Trauma. 1982;22(9):741–6.PubMedCrossRefGoogle Scholar
  130. 130.
    Napolitano LM, Kurek S, Luchette FA, Corwin HL, Barie PS, Tisherman SA, et al. Clinical practice guideline: red blood cell transfusion in adult trauma and critical care. Crit Care Med. 2009;37(12):3124–57.PubMedCrossRefGoogle Scholar
  131. 131.
    Shander A. Emerging risks and outcomes of blood transfusion in surgery. Semin Hematol. 2004;41(1 Suppl 1):117–24.PubMedCrossRefGoogle Scholar
  132. 132.
    Moore SB. Transfusion-related acute lung injury (TRALI): clinical presentation, treatment, and prognosis. Crit Care Med. 2006;34(5 Suppl):S114–7.PubMedCrossRefGoogle Scholar
  133. 133.
    Toy P, Gajic O, Bacchetti P, Looney MR, Gropper MA, Hubmayr R, et al. Transfusion-related acute lung injury: incidence and risk factors. Blood. 2012;119(7):1757–67.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Shander A, Popovsky MA. Understanding the consequences of transfusion-related acute lung injury. Chest. 2005;128(5 Suppl 2):598S–604.PubMedCrossRefGoogle Scholar
  135. 135.
    Vlaar AP, Hofstra JJ, Determann RM, Veelo DP, Paulus F, Kulik W, et al. The incidence, risk factors, and outcome of transfusion-related acute lung injury in a cohort of cardiac surgery patients: a prospective nested case-control study. Blood. 2011;117(16):4218–25.PubMedCrossRefGoogle Scholar
  136. 136.
    Bolton-Maggs PH, Cohen H. Serious hazards of transfusion (SHOT) haemovigilance and progress is improving transfusion safety. Br J Haematol. 2013;163(3):303–14.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Lucas G, Win N, Calvert A, Green A, Griffin E, Bendukidze N, et al. Reducing the incidence of TRALI in the UK: the results of screening for donor leucocyte antibodies and the development of national guidelines. Vox Sang. 2012;103(1):10–7.PubMedCrossRefGoogle Scholar
  138. 138.
    Popovsky MA. Pulmonary consequences of transfusion: TRALI and TACO. Transfus Apher Sci. 2006;34(3):243–4.PubMedCrossRefGoogle Scholar
  139. 139.
    Narick C, Triulzi DJ, Yazer MH. Transfusion-associated circulatory overload after plasma transfusion. Transfusion. 2012;52(1):160–5.PubMedCrossRefGoogle Scholar
  140. 140.
    Li G, Rachmale S, Kojicic M, Shahjehan K, Malinchoc M, Kor DJ, et al. Incidence and transfusion risk factors for transfusion-associated circulatory overload among medical intensive care unit patients. Transfusion. 2011;51(2):338–43.PubMedCrossRefGoogle Scholar
  141. 141.
    Opelz G, Sengar DP, Mickey MR, Terasaki PI. Effect of blood transfusions on subsequent kidney transplants. Transplant Proc. 1973;5(1):253–9.PubMedGoogle Scholar
  142. 142.
    Vamvakas EC, Blajchman MA. Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention. Blood. 2009;113(15):3406–17.PubMedCrossRefGoogle Scholar
  143. 143.
    Triulzi DJ, Yazer MH. Clinical studies of the effect of blood storage on patient outcomes. Transfus Apher Sci. 2010;43(1):95–106.PubMedCrossRefGoogle Scholar
  144. 144.
    Refaai MA, Blumberg N. Transfusion immunomodulation from a clinical perspective: an update. Expert Rev Hematol. 2013;6(6):653–63.PubMedCrossRefGoogle Scholar
  145. 145.
    Walsh TS, Saleh EE, Lee RJ, McClelland DB. The prevalence and characteristics of anaemia at discharge home after intensive care. Intensive Care Med. 2006;32(8):1206–13.PubMedCrossRefGoogle Scholar
  146. 146.
    Bateman AP, McArdle F, Walsh TS. Time course of anemia during six months follow up following intensive care discharge and factors associated with impaired recovery of erythropoiesis. Crit Care Med. 2009;37(6):1906–12.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

<SimplePara><Emphasis Type="Bold">Open Access</Emphasis> This chapter is licensed under the terms of the Creative Commons Attribution-NonCommercial 2.5 International License (, which permits any noncommercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. </SimplePara> <SimplePara>The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.</SimplePara>

Authors and Affiliations

  • Aryeh Shander
    • 1
  • Lena M. Napolitano
    • 2
  • Margit Kaufman
    • 1
  1. 1.Anesthesiology and Critical Care MedicineEnglewood Hospital and Medical CenterEnglewoodUSA
  2. 2.Department of SurgeryUniversity of Michigan Health SystemAnn ArborUSA

Personalised recommendations