for diagnosing cobalamin and folate deficiencies. Am J Med. 1994; 96(3):239‐46.38 38. Langan R, Zawistoski K. Update on Vitamin B12 Deficiency. Am Fam Physician. 2011; 83(12):1425‐30.
39 39. Wong CW. Vitamin B12 deficiency in the elderly: is it worth screening? Hong Kong Med J. 20015; 21:155‐64.
40 40. Carmel R. Green R, Rosenblatt DS, et al. Update on cobalamin, folate, and homocysteine. Hematology Am Soc Hematol Educ Program. 2003:62‐81.
41 41. Carmel R. Cobalamin, the stomach, and aging. Am J Clin Nutr. 1997; 66:750‐9.
42 42. Vidal‐Alaball J, Butler C, Cannings‐John R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cocahrane Database Syst Rev. 2005;(3):CD004655.
43 43. US Department of Health and Human Services Food and Drug Administration. Food standards: amendment of the standards of identity for enriched grain product to require addition of folic acid. Fed Regist. 1996; 61:8781.
44 44. Sanford AM, Flaherty JH. Do nutrients play a role in delirium? Curr Opin Clin Nutr Metab Care. 2014; 17(1):45‐50.
45 45. Khan KM, Jialal I. Folic Acid (Folate) Deficiency. StatPearls Publishing; 2020.
46 46. Scott J, Weir D. Folate/vitamin B12 inter‐relationshiprs. Essays Biochem. 1994; 28:63‐72.
47 47. Sobczynska‐Malefora A, Harrington D. Laboratory assessment of folate (vitamin B9 status). J Clin Path. 2018; 71(11):949‐56.
48 48. Joosten E, Lioen P. Iron deficiency anemia and anemia of chronic disease in geriatric hospitalized patients: how frequent are comorbidities as an additional explanation for the anemia? Geriatr Gerontol Int. 2014; 15(8):931‐5.
49 49. Careaga M, Moize V, Flores L, et al. Inflammation and iron status in bariatric surgery candidates. Surg Obes Relat Dis. 2015; 11(4):906‐11.
50 50. Pietrangelo A. Physiology of iron transport and the hemochromatosis gene. Am J Physiol Gastrointest Liver Physiol. 2002; 282:G403‐414.
51 51. 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; 113:1271‐6.
52 52. Jelkmann W. Proinflammatory cytokines lowering erythropoietin production. J Interferon Cytokine Res. 1998; 18:555‐9.
53 53. Moldawer LL, Marano MA, Wei H, et al. Cachectin/tumor necrosis factor‐alpha alters red blood cell kinetics and induces anemia in vivo. FASEB J. 1989; 3:1637‐43.
54 54. Maciejewski JP, Selleri C, Sato T, et al. Nitric oxide suppression of human hematopoiesis in vitro: contribution to inhibitory action of interferon‐gamma and tumor necrosis factor‐alpha. J Clin Invest. 1995; 96:1085‐92.
55 55. Skikne BS, Punnonen K, Caldron PH, et al. Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index. Am J Hematol. 2011; 86(11):923‐27.
56 56. Weiss G. Iron and immunity: a double‐edged sword. Eur J Clin Invest. 2002; 32:Supple 1 70‐80.
57 57. Kletzmayr J, Sunder‐Plassmann G, Horl WH. High dose intravenous iron: a note of caustion. Nephrol Dial transplant. 2002; 17:962‐5.
58 58. Weiss G, Goodnough L. Anemia of chronic disease. N Engl J Med. 2005; 352:1011‐23.
59 59. Brugnara C. Iron deficiency and erythropoiesis: new diagnostic approaches. Clin Chem. 203; 49:1573‐8.
60 60. Rizzo JD, Lichtin AE, Woolf SH, et al. Use of epoetin in patients with cancer: evidence‐based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. J Clin Oncol. 2002; 20:4083‐4107.
61 61. National Kidney Foundation. KEEP 2004 annual data report. Am J Kidney Dis. 2005; 45(suppl 2):S1‐80.
62 62. McClellan W, Resnick B, Lei L, et al. Prevalence and severity of chronic kidney disease and anemia in the nursing home population. J Am Med Dir Assoc. 2010; 11:33‐41.
63 63. Ma JZ, Ebben J, Xia H, et al. Hematocrit level and associated mortality in hemodialysis patients. J Am Soc Nephrol. 1999; 10:610‐9.
64 64. Moreno F, Sanz‐Guajardo D, Lopez‐Gomez, JM, et al. Increasing the hematocrit has a beneficial effect on quality of life and is safe in selected hemodialysis patients: Spanish Cooperative Renal Patients Quality of Life Study Group of the Spanish Society of Nephrology. J Am Soc Nephrol. 2000: 11:335‐42.
65 65. Besarab A, Ayyoub F. Anemia in renal disease: Diseases of the Kidney and Urinary Tract, 8th ed. Lippincott Williams and Wilkins; 2007:2406–2430.
66 66. Hunsicker L, Levey A. Progression of chronic renal disease: mechanisms, risk factors, and testing of interventions. The Principles and Practice of Nephrology. Mosby; 1995:622‐31.
67 67. Anapalahan M, Savvas S, Lo K, et al. Chronic idiopathic normocytic anaemia in older people: the risk factors and the role of age‐associated renal impairment. Aging Clin Exp Res. 2017; 29:147‐55.
68 68. Nielson O, Thayson J. Erythropoietin deficiency in acute renal failure. Lancet. 1989; 1:634‐5.
69 69. Cotes PM, Tam RC, Reed P, et al. An immunological cross‐reactant of erythropoietin in serum which may invalidate EPO radioimmunoassay. BR J Haematol. 1989; 73:265‐68.
70 70. NKF‐K/DOQI Clinical Practice Guidelines for anemia of chronic kidney disease: update 2000. Am J Kidney Dis. 2001: 37:Suppl 1:S182–S238.
71 71. Phrommintikul A, Haas SJ, Elsik M, et al. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta‐analysis. Lancet. 2007; 369:381‐88.
72 72. KDOQI, National Kidney Foundation. KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am J Kidney Dis. 2006; 47(5 Supple 3):S11‐145.
73 73. Bennett CL, Becker PS, Kraut EH et al. Intersecting guidelines: administering erythropoiesis‐stimulating agents to chronic kidney disease patients with cancer. Semin Dial. 2009; 22:1‐4.
CHAPTER 23 Disseminated intravascular coagulation
Kingsley K. Hampton
Royal Hallamshire Hospital, Sheffield, UK
Introduction
Disseminated intravascular coagulation (DIC) is a failure of haemostatic homeostasis (Figure 23.1). The haemostatic system comprises five components: the coagulation cascade, the fibrinolytic cascade, platelets, the natural anticoagulant pathway, and vascular endothelial cells. It is a complex system that normally maintains blood fluidity when blood is confined within the intravascular vessels but can trigger rapid and localized coagulation if vascular integrity is breached. The intravascular space usually contains no exposed tissue factor, but all cells outside the vascular system express tissue factor in their cell membranes that initiates coagulation through the extrinsic pathway, as tissue factor binds to Factor VII and
