Systemic consequences of intestinal inflammation

  • Konstantinos A. Papadakis
  • Maria T. Abreu


Inflammatory Bowel Disease Ulcerative Colitis Inflammatory Bowel Disease Patient Intestinal Inflammation Anticardiolipin Antibody 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Chrousos GP. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 1995; 332: 1351–62.PubMedGoogle Scholar
  2. 2.
    Papanicolaou DA, Wilder RL, Manolagas SC, Chrousos GP. The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med 1998; 128: 127–37.PubMedGoogle Scholar
  3. 3.
    van Deventer SJ, Buller HR, ten Cate JW, Aarden LA, Hack CE, Sturk A. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood 1990; 76: 2520–6.PubMedGoogle Scholar
  4. 4.
    Kotler D. Cachexia. Annals Intern Med 2000; 133: 622–34.Google Scholar
  5. 5.
    Tracey KJ, Morgello S, Koplin B et al. Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia. J Clin Invest 1990; 86: 2014–24.PubMedGoogle Scholar
  6. 6.
    Tracey KJ, Cerami A. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annu Review of Med 1994; 45: 491–503.Google Scholar
  7. 7.
    Papadakis KA, Targan SR. Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med 2000; 51: 289–98.PubMedGoogle Scholar
  8. 8.
    Papadakis KA, Targan SR. Tumor necrosis factor: biology and therapeutic inhibitors. Gastroenterology 2000; 119: 1148–57.PubMedGoogle Scholar
  9. 9.
    O’Neill LA, Dinarello CA. The IL-1 receptor/toll-like receptor superfamily: crucial receptors for inflammation and host defense. Immunol Today 2000; 21: 206–9.PubMedGoogle Scholar
  10. 10.
    Howard AD, Kostura MJ, Thornberry N et al. IL-1-converting enzyme requires aspartic acid residues for processing of the IL-1 beta precursor at two distinct sites and does not cleave 31-kDa IL-1 alpha. J Immunol 1991; 147: 2964–9.PubMedGoogle Scholar
  11. 11.
    Rosenwasser LJ. Biologic activities of IL-1 and its role in human disease. J Allergy Clin Immunol 1998; 102: 344–50.PubMedGoogle Scholar
  12. 12.
    Dinarello CA. Proinflammatory cytokines. Chest 2000; 118: 503–8.PubMedGoogle Scholar
  13. 13.
    Ershler WB, Keller ET. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med 2000; 51: 245–70.PubMedGoogle Scholar
  14. 14.
    Cressman DE, Greenbaum LE, DeAngelis RA et al. Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science 1996; 274: 1379–83.PubMedGoogle Scholar
  15. 15.
    Streetz KL, Luedde T, Manns MP, Trautwein C. Interleukin 6 and liver regeneration. Gut 2000; 47: 309–12.PubMedGoogle Scholar
  16. 16.
    Nielsen OH, Vainer B, Madsen SM, Seidelin JB, Heegaard NH. Established and emerging biological activity markers of inflammatory bowel disease. Am J Gastroenterol 2000; 95: 359–67.PubMedGoogle Scholar
  17. 17.
    Mahida YR, Ceska M, Effenberger F, Kurlak L, Lindley I, Hawkey CJ. Enhanced synthesis of neutrophil-activating peptide-1/interleukin-8 in active ulcerative colitis. Clin Sci 1992; 82: 273–5.PubMedGoogle Scholar
  18. 18.
    Farmer RG, Hawk WA, Turnbull RB Jr. Clinincal patterns in Crohn’s disease: a statistical study of 615 cases. Gastroenterology 1975; 68: 627–35.PubMedGoogle Scholar
  19. 19.
    Sparberg M, Fennessy J, Kirsner JB. Ulcerative proctitis and mild ulcerative colitis: a study of 220 patients. Medicine 1966; 45: 391–412.PubMedGoogle Scholar
  20. 20.
    Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation [published erratum appears in N Engl J Med 1999; 340: 1376]. N Engl J Med 1999; 340: 448–54.PubMedGoogle Scholar
  21. 21.
    Moldawer LL, Copeland EM IIIrd. Proinflammatory cytokines, nutritional support, and the cachexia syndrome: interactions and therapeutic options. Cancer 1997; 79: 1828–39.PubMedGoogle Scholar
  22. 22.
    Plata-Salaman CR. Food intake suppression by growth factors and platelet peptides by direct action in the central nervous system. Neurosci Lett 1988; 94: 161–6.PubMedGoogle Scholar
  23. 23.
    Sarraf P, Frederich RC, Turner EM et al. Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J Exp Med 1997; 185: 1715.Google Scholar
  24. 24.
    Both H, Torp-Pedersen K, Kreiner S, Hendriksen C, Binder V. Clinical appearance at diagnosis of ulcerative colitis and Crohn’s disease in a regional patient group. Scand J Gastroenterol 1983; 18: 987–91.PubMedGoogle Scholar
  25. 25.
    Dinarello CA. Cytokines as endogenous pyrogens. J Infect Dis 1999; 179(Suppl 2): S294–304.PubMedGoogle Scholar
  26. 26.
    Castell JV, Gomez-Lechon MJ, David M et al. Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes. FEBS Lett 1989; 242: 237–9.PubMedGoogle Scholar
  27. 27.
    Fattori E, Cappelletti M, Costa P et al. Defective inflammatory response in interleukin 6-deficient mice. J Exp Med 1994; 180: 1243–50.PubMedGoogle Scholar
  28. 28.
    Betz UAK, Bloch W, van den Broek M et al. Postnatally induced inactivation of gp130 in mice results in neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects. J Exp Med 1998; 188: 1955–65.PubMedGoogle Scholar
  29. 29.
    Gershov D, Kim S, Brot N, Elkon K. C-reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity. J Exp Med 2000; 192: 1353–64.PubMedGoogle Scholar
  30. 30.
    Greenstein AJ, Sachar DB, Panday AK et al.: Amyloidosis and inflammatory bowel disease. A 50-year experience with 25 patients. Medicine 1992; 71: 261–70.PubMedGoogle Scholar
  31. 31.
    Kurzrock R, Redman J, Cabanillas F, Jones D, Rothberg J, Talpaz M. Serum interleukin 6 levels are elevated in lymphoma patients and correlate with survival in advanced Hodgkin’s disease and with B symptoms. Cancer Res 1993; 53: 2118–22.PubMedGoogle Scholar
  32. 32.
    Gasche C. Anemia in IBD: the overlooked villain. Inflammat Bowel Dis 2000; 6: 142–50; discussion 151.Google Scholar
  33. 33.
    Gasche C, Dejaco C, Waldhoer T et al. Intravenous iron and erythropoietin for anemia associated with Crohn disease. A randomized, controlled trial. Ann Intern Med 1997; 126: 782–7.PubMedGoogle Scholar
  34. 34.
    Horina JH, Petritsch W, Schmid CR et al. Treatment of anemia in inflammatory bowel disease with recombinant human erythropoietin: results in three patients. Gastroenterology 1993; 104: 1828–31.PubMedGoogle Scholar
  35. 35.
    Gasche C, Reinisch W, Lochs H et al. Anemia in Crohn’s disease. Importance of inadequate erythropoietin production and iron deficiency. Dig Dis Sci 1994; 39: 1930–4.PubMedGoogle Scholar
  36. 36.
    Beeken WL. Remediable defects in Crohn disease: a prospective study of 63 patients. Arch Intern Med 1975; 135: 686–90.PubMedGoogle Scholar
  37. 37.
    Gold Y, Reif S. [Aphthous stomatitis as a first manifestation of Crohn’s disease in a 5 year-old boy]. Harefuah 1998; 135: 364–6, 407.PubMedGoogle Scholar
  38. 38.
    Froom P, Benbassat J, Kiwelowicz A, Erel J, Davidson B, Ribak J. Significance of low hematocrit levels in asymptomatic young adults: results of 15 years follow-up. Aviat Space Environ Med 1999; 70: 983–6.PubMedGoogle Scholar
  39. 39.
    Menachem Y, Weizman Z, Locker C, Odes S. Clinical characteristics of Crohn’s disease in children and adults. Harefuah 1998; 134: 173–5, 247.PubMedGoogle Scholar
  40. 40.
    Smith AD, Cochran KM. Serum ferritin: it may guide the diagnosis of the anaemic patient. Scot Med J 1997; 42: 182–3.PubMedGoogle Scholar
  41. 41.
    Gasche C, Dejaco C, Reinisch W et al. Sequential treatment of anemia in ulcerative colitis with intravenous iron and erythropoietin. Digestion 1999; 60: 262–7.PubMedGoogle Scholar
  42. 42.
    Macdougall IC. Strategies for iron supplementation: oral versus intravenous. Kidney Int (Suppl.) 1999; 69: S61–6.Google Scholar
  43. 43.
    Hamstra RD, Block MH, Schocket AL. Intravenous iron dextran in clinical medicine. J Am Med Assoc 1980; 243: 1726–31.Google Scholar
  44. 44.
    Dyer N, Dawson A: Malnutrition and malabsorption in Crohn’s disease with references to the effect of surgery. Br J Surg 1973; 60: 134–40.PubMedGoogle Scholar
  45. 45.
    Dyer NH, Child JA, Mollin DL, Dawson AM. Anaemia in Crohn’s disease. Q J Med 1972; 41: 419–36.PubMedGoogle Scholar
  46. 46.
    Thompson W, Wrathell E. The relation between ileal resection and vitamin B12 absorption. Can J Surg 1977; 20: 461–4.PubMedGoogle Scholar
  47. 47.
    Fone D et al. [58]Co B-12 absorption after gastrectomy, ileal resection and in coeliac disorders. Gut 1961; 2: 218.PubMedGoogle Scholar
  48. 48.
    Lee G. Pernicious anemia and other causes of vitamin B12 (cobalamin) deficiency. In: Lee G (ed.), Wintrobe’s Clinical Hematology, 10th edn. Baltimore: Lippincott, Williams & Wilkins, 1999;956.Google Scholar
  49. 49.
    Spiegel JE, Willenbucher RF. Rapid development of severe copper deficiency in a patient with Crohn’s disease receiving parenteral nutrition. J Parent Ent Nutr 1999; 23: 169–72.Google Scholar
  50. 50.
    Means RT Jr. Erythropoietin in the treatment of anemia in chronic infectious, inflammatory, and malignant diseases. Curr Opin Hematol 1995; 2: 210–3.PubMedGoogle Scholar
  51. 51.
    Means RT Jr. Advances in the anemia of chronic disease. Int J Hematol 1999; 70: 7–12.PubMedGoogle Scholar
  52. 52.
    Schreiber S, Howaldt S, Schnoor M et al. Recombinant erythropoietin for the treatment of anemia in inflammatory bowel disease. N Engl J Med 1996; 334: 619–23.PubMedGoogle Scholar
  53. 53.
    Koury M, Bondurant M. The molecular mechanism of erythropoietin action. Eur J Biochem 1992; 210: 649–63.PubMedGoogle Scholar
  54. 54.
    Jelkmann WE, Fandrey J, Frede S, Pagel H: Inhibition of erythropoietin production by cytokines. Implications for the anemia involved in inflammatory states. Ann NY Acad Sci 1994; 718: 300–9; discussion 309–11.PubMedGoogle Scholar
  55. 55.
    Jelkmann W. Proinflammatory cytokines lowering erythropoietin production. J Interferon Cytokine Res 1998; 18: 555–9.PubMedGoogle Scholar
  56. 56.
    Faquin WC, Schneider TJ, Goldberg MA. Effect of inflammatory cytokines on hypoxia-induced erythropoietin production. Blood 1992; 79: 1987–94.PubMedGoogle Scholar
  57. 57.
    Gunnell J, Yeun JY, Depner TA, Kaysen GA. Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients. Am J Kidney Dis 1999; 33: 63–72.PubMedGoogle Scholar
  58. 58.
    Nordstrom D, Lindroth Y, Marsal L et al. Availability of iron and degree of inflammation modifies the response to recombinant human erythropoietin when treating anemia of chronic disease in patients with rheumatoid arthritis. Rheumatollnt 1997; 17: 67–73.Google Scholar
  59. 59.
    Tarng DC, Huang TP, Chen TW, Yang WC. Erythropoietin hyporesponsiveness: from iron deficiency to iron overload. Kidney Int (Suppl.) 1999; 69: S107–18.Google Scholar
  60. 60.
    Lennard L, Murphy M, Maddocks J: Severe megaloblastic anaemia associated with abnormal azathioprine metabolism. Br J Clin Pharmacol 1984; 17: 171.PubMedGoogle Scholar
  61. 61.
    Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 1980; 32: 651–62.PubMedGoogle Scholar
  62. 62.
    Schutz E, Gummert J, Armstrong VW, Mohr FW, Oellerich M. Azathioprine pharmacogenetics: the relationship between 6-thioguanine nucleotides and thiopurine methyltransferase in patients after heart and kidney transplantation. Eur J Clin Chem Clin Biochem 1996; 34: 199–205.PubMedGoogle Scholar
  63. 63.
    Lennard L, Van Loon JA, Lilleyman JS, Weinshilboum RM. Thiopurine pharmacogenetics in leukemia: correlation of erythrocyte thiopurine methyltransferase activity and 6-thioguanine nucleotide concentrations. Clin Pharmacol Therl 987; 41: 18–25.Google Scholar
  64. 64.
    Lowry PW, Szumlanski CL, Weinshilboum RM, Sandborn WJ. Balsalazide and azathiprine or 6-mercaptopurine: evidence for a potentially serious drug interaction [Letter; comment]. Gastroenterology 1999; 116: 1505–6.PubMedGoogle Scholar
  65. 65.
    Lewis LD, Benin A, Szumlanski CL et al. Olsalazine and 6-mercaptopurine-related bone marrow suppression: a possible drug-drug interaction [Published erratum appears in Clin Pharmacol Ther 2000; 67:431]. Clin Pharmacol Ther 1997; 62: 464–75.PubMedGoogle Scholar
  66. 66.
    Szumlanski CL, Weinshilboum RM. Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6-mercaptopurine and azathioprine. Br J Clin Pharmacol 1995; 39: 456–9.PubMedGoogle Scholar
  67. 67.
    Swinson CM, Perry J, Lumb M, Levi AJ. Role of sulphasalazine in the aetiology of folate deficiency in ulcerative colitis. Gut 1981; 22: 456–61.PubMedGoogle Scholar
  68. 68.
    Longstreth G, Green R. Folate status in patients receiving maintenance doses of sulfasalazine. Arch Intern Med 1983; 143: 902.PubMedGoogle Scholar
  69. 69.
    Das KM, Eastwood MA, McManus JP, Sircus W. Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype. N Engl J Med 1973; 289: 491–5.PubMedGoogle Scholar
  70. 70.
    Abboudi ZH, Marsh JC, Smith-Laing G, Gordon-Smith EC. Fatal aplastic anaemia after mesalazine [Letter]. Lancet 1994; 343: 542.PubMedGoogle Scholar
  71. 71.
    Dunn AM, Kerr GD. Pure red cell aplasia associated with sulphasalazine [Letter]. Lancet 1981; 2: 1288.PubMedGoogle Scholar
  72. 72.
    Daneshmend T. Mesalazine-associated thrombocytopenia. Lancet 1991; 337: 1297–8.PubMedGoogle Scholar
  73. 73.
    Wyatt S, Joyner M, Daneshmend T. Filgrastim for mesalazine-associated neutropenia. Lancet 1993; 341: 1476.PubMedGoogle Scholar
  74. 74.
    Gumaste V, Greenstein AJ, Meyers R, Sachar DB. Coombspositive autoimmune hemolytic anemia in ulcerative colitis. Dig Dis Sci 1989; 34: 1457–61.PubMedGoogle Scholar
  75. 75.
    Bell DW, Urban E, Sears DA, Walder Al, Ostrower VS. Ulcerative colitis complicated by autoimmune hemolytic anemia. S Med J 1981; 74: 359–61.Google Scholar
  76. 76.
    Altman AR, Maltz C, Janowitz HD. Autoimmune hemolytic anemia in ulcerative colitis: report of three cases, review of the literature, and evaluation of modes of therapy. Dig Dis Sci 1979; 24: 282–5.PubMedGoogle Scholar
  77. 77.
    Ma A, Datta M, Margosian E, Chen J, Horak I: T cells, but not B cells, are required for bowel inflammation in inter-leukin 2-deficient mice. J Exp Med 1995; 182: 1567–72.PubMedGoogle Scholar
  78. 78.
    Ramakrishna R, Manoharan A. Auto-immune haemolytic anaemia in ulcerative colitis. Acta Haematol 1994; 91: 99–102.PubMedGoogle Scholar
  79. 79.
    Giannadaki E, Potamianos S, Roussomoustakaki M, Kyriakou D, Fragkiadakis N, Manousos ON. Autoimmune hemolytic anemia and positive Coombs test associated with ulcerative colitis. Am J Gastroenterol 1997; 92: 1872–4.PubMedGoogle Scholar
  80. 80.
    Teplitsky V, Virag I, Halabe A. Immune complex haemolytic anaemia associated with sulfasalazine. Br Med J 2000; 320: 1113.Google Scholar
  81. 81.
    Mechanick JI. Coombs’ positive hemolytic anemia following sulfasalazine therapy in ulcerative colitis: case reports, review, and discussion of pathogenesis. Mount Sinai J Med 1985; 52: 667–70.Google Scholar
  82. 82.
    van Hees PA, van Elferen LW, van Rossum JM, van Tongeren JH. Hemolysis during salicylazosulfapyridine therapy. Am J Gastroenterol 1978; 70: 501–5.PubMedGoogle Scholar
  83. 83.
    Yates P, Macht LM, Williams NA, Elson CJ. Red cell autoantibody production by colonic mononuclear cells from a patient with ulcerative colitis and autoimmune haemolytic anaemia. Br J Haematol 1992; 82: 753–6.PubMedGoogle Scholar
  84. 84.
    Murphy PT, Cunney R, Nolan A, O’Donnell JR. Autoimmune haemolytic anaemia associated with ulcerative colitis. Irish Med J 1996; 89: 172–3.Google Scholar
  85. 85.
    Cohen SM, Rosenthal DS, Karp PJ. Ulcerative colitis and erythrocyte G6PD deficiency. Salicylazosulfapyridine-provoked hemolysis. J Am Med Assoc 1968; 205: 528–30.Google Scholar
  86. 86.
    Dahlback B, Blood coagulation. Lancet 2000; 355: 1627–32.PubMedGoogle Scholar
  87. 87.
    Aichbichler BW, Petritsch W, Reicht GA et al. Anti-cardiolipin antibodies in patients with inflammatory bowel disease. Dig Dis Sci 1999; 44: 852–6.PubMedGoogle Scholar
  88. 88.
    Schapira M, Henrion J, Ravoet C et al. Thromboembolism in inflammatory bowel disease. Acta Gastroenterol Belg 1999; 62: 182–6.PubMedGoogle Scholar
  89. 89.
    Talbot RW, Heppell J, Dozois RR, Beart RW, Jr. Vascular complications of inflammatory bowel disease. Mayo Clin Procl 986; 61: 140–5.Google Scholar
  90. 90.
    Jackson LM, O’Gorman PJ, O’Connell J, Cronin CC, Cotter KP, Shanahan F. Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden. Q J Med 1997; 90: 183–8.Google Scholar
  91. 91.
    Koenigs KP, McPhedran P, Spiro HM. Thrombosis in inflammatory bowel disease. J Clin Gastroenterol 1987; 9: 627–31.PubMedGoogle Scholar
  92. 92.
    Johns DR. Cerebrovascular complications of inflammatory bowel disease. Am J Gastroenterol 1991; 86: 367–70.PubMedGoogle Scholar
  93. 93.
    Carmona MA, Jaume Anselmi F, Ramirez Rivera J. Cerebral thrombosis and vasculitis: an uncommon complication of ulcerative colitis. Bol Asoc Med Puerto Rico 2000; 92: 9–11.Google Scholar
  94. 94.
    Papi C, Ciaco A, Acierno G et al. Severe ulcerative colitis, dural sinus thrombosis, and the lupus anticoagulant. Am J Gastroenterol 1995; 90: 1514–7.PubMedGoogle Scholar
  95. 95.
    Musio F, Older SA, Jenkins T, Gregorie EM. Case report: cerebral venous thrombosis as a manifestation of acute ulcerative colitis. Am J Med Sci 1993; 305: 28–35.PubMedGoogle Scholar
  96. 96.
    Markowitz RL, Ment LR, Gryboski JD. Cerebral thromboembolic disease in pediatric and adult inflammatory bowel disease: case report and review of the literature. J Pediatr Gastroenterol Nutr 1989; 8: 413–20.PubMedGoogle Scholar
  97. 97.
    Bansal R, Goel A. Ulcerative colitis with sagittal sinus thrombosis with normal coagulation profile. Ind J Gastroenterol 2000; 19: 88–9.Google Scholar
  98. 98.
    Derdeyn CP, Powers WJ. Isolated cortical venous thrombosis and ulcerative colitis. Am J Neuroradiol 1998; 19: 488–90.PubMedGoogle Scholar
  99. 99.
    Crowe A, Taffinder N, Layer GT, Irvine A, Nicholls RJ. Portal vein thrombosis in a complicated case of Crohn’s disease. Postgrad Med J 1992; 68: 291–3.PubMedGoogle Scholar
  100. 100.
    Miyazaki Y, Shinomura Y, Kitamura S et al. Portal vein thrombosis associated with active ulcerative colitis: percutaneous transhepatic recanalization. Am J Gastroenterol 1995; 90: 1533–4.PubMedGoogle Scholar
  101. 101.
    Chesner IM, Muller S, Newman J. Ulcerative colitis com plicated by Budd-Chiari syndrome. Gut 1986; 27: 1096–100.PubMedGoogle Scholar
  102. 102.
    Maccini DM, Berg JC, Bell GA. Budd-Chiari syndrome and Crohn’s disease. An unreported association. Dig Dis Sci 1989; 34: 1933–6.PubMedGoogle Scholar
  103. 103.
    Brinson RR, Curtis WD, Schuman BM, Mills LR. Recovery from hepatic vein thrombosis (Budd Chiari syndrome) complicating ulcerative colitis. Dig Dis Sci 1988; 33: 1615–20.PubMedGoogle Scholar
  104. 104.
    Praderio L, Dagna L, Longhi P, Rubin G, Sabbadini MG. Budd Chiari syndrome in a patient with ulcerative colitis: association with anticardiolipin antibodies. J Clin Gastroenterol 2000; 30: 203–4.PubMedGoogle Scholar
  105. 105.
    Halliday CE, Farthing MJ. Arterial thrombosis in Crohn’s disease. Med J Austr 1988; 149: 559–60.Google Scholar
  106. 106.
    Kyrle PA, Minar E, Hirschl M et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000; 343: 457–62.PubMedGoogle Scholar
  107. 107.
    Chiarantini E, Valanzano R, Liotta AA. Hemostatic abnormalities in inflammatory bowel disease. Thromb Res 1996; 82: 137–46.PubMedGoogle Scholar
  108. 108.
    Smith CJ, Haire WD, Kaufman SS, Mack DR. Determination of prothrombin activation fragments in young patients with inflammatory bowel disease. Am J Gastroenterol 1996; 91: 1221–5.PubMedGoogle Scholar
  109. 109.
    Chamouard P, Grunebaum L, Wiesel ML et al. Prothrombin fragment 1 + 2 and thrombin-antithrombin III complex as markers of activation of blood coagulation in inflammatory bowel diseases. Eur J Gastroenterol Hepatol 1995; 7: 1183–8.PubMedGoogle Scholar
  110. 110.
    Souto JC, Martinez E, Roca M et al. Prothrombotic state and signs of endothelial lesion in plasma of patients with inflammatory bowel disease. Dig Dis Sci 1995; 40: 1883–9.PubMedGoogle Scholar
  111. 111.
    Koutroubakis IE, Sfiridaki A, Mouzas IA et al. Resistance to activated protein C and low levels of free protein S in Greek patients with inflammatory bowel disease. Am J Gastroenterol 2000; 95: 190–4.PubMedGoogle Scholar
  112. 112.
    Lee LC, Spittell JA, Jr, Sauer WG, Owen CA, Jr, Thompson JH, Jr. Hypercoagulability associated with chronic ulcerative colitis: changes in blood coagulation factors. Gastroenterology 1968; 54: 76–85.PubMedGoogle Scholar
  113. 113.
    Braverman D, Bogoch A. Arterial thrombosis in ulcerative colitis. Am J Dig Dis 1978; 23: 1148–50.PubMedGoogle Scholar
  114. 114.
    Aadland E, Odegaard OR, Roseth A, Try K. Free protein S deficiency in patients with Crohn’s disease. Scand J Gastroenterol 1994; 29: 333–5.PubMedGoogle Scholar
  115. 115.
    Talstad I, Rootwelt K, Gjone E. Thrombocytosis in ulcerative colitis and Crohn’s disease. Scand J Gastroenterol 1973; 8: 135–8.PubMedGoogle Scholar
  116. 116.
    Lam A, Borda I, Inwood M, Thomson S. Coagulation studies in ulcerative colitis and Crohn’s disease. Gastroenterology 1975; 68: 245–51.PubMedGoogle Scholar
  117. 117.
    Morowitz D, Allen L, Kirsner J. Thrombocytosis in chronic inflammatory bowel disease. Ann Intern Med 1968; 68: 1013–21.PubMedGoogle Scholar
  118. 118.
    Vecchi M, Cattaneo M, de Franchis R, Mannucci PM. Risk of thromboembolic complications in patients with inflammatory bowel disease. Study of hemostasis measurements. Int J Clin Lab Res 1991; 21: 165–70.PubMedGoogle Scholar
  119. 119.
    Heneghan MA, Cleary B, Murray M, O’Gorman TA, McCarthy CF. Activated protein C resistance, thrombophilia, and inflammatory bowel disease. Dig Dis Sci 1998; 43: 1356–61.PubMedGoogle Scholar
  120. 120.
    Webberley MJ, Hart MT, Melikian V. Thromboembolism in inflammatory bowel disease: role of platelets. Gut 1993; 34: 247–51.PubMedGoogle Scholar
  121. 121.
    Chiarantini E, Valanzano R, Liotta AA et al. Persistence of hemostatic alterations in patients affected by Crohn’s disease after bowel surgery. Thromb Res 1997; 87: 539–46.PubMedGoogle Scholar
  122. 122.
    Heits F, Stahl M, Ludwig D, Stange EF, Jelkmann W. Elevated serum thrombopoietin and interleukin-6 concentrations in thrombocytosis associated with inflammatory bowel disease. J Interferon Cytokine Res 1999; 19: 757–60.PubMedGoogle Scholar
  123. 123.
    Sands BE, Bank S, Sninsky CA et al. Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn’s disease. Gastroenterology 1999; 117:58–64.PubMedGoogle Scholar
  124. 124.
    Hudson M, Chitolie A, Hutton RA, Smith MS, Pounder RE, Wakefield AJ. Thrombotic vascular risk factors in inflammatory bowel disease. Gut 1996; 38: 733–7.PubMedGoogle Scholar
  125. 125.
    Chamouard P, Grunebaum L, Wiesel ML et al. Prevalence and significance of anticardiolipin antibodies in Crohn’s disease. Dig Dis Sci 1994; 39: 1501–4.PubMedGoogle Scholar
  126. 126.
    Koutroubakis IE, Petinaki E, Anagnostopoulou E et al. Anti-cardiolipin and anti-beta2-glycoprotein I antibodies in patients with inflammatory bowel disease. Dig Dis Sci 1998; 43:2507–12.PubMedGoogle Scholar
  127. 127.
    Vianna JL, D’Cruz DP, Khamashta MA, Asherson RA, Hughes GR. Anticardiolipin antibodies in a patient with Crohn’s disease and thrombosis. Clin Exp Rheumatol 1992; 10: 165–8.PubMedGoogle Scholar
  128. 128.
    Olds RJ, Fitches AC, Geary CP. The multigenic basis for venous thrombosis. Br J Haematol 2000; 109: 508–11.PubMedGoogle Scholar
  129. 129.
    Dahlback B. New molecular insights into the genetics of thrombophilia. Resistance to activated protein C caused by Arg (506) to Gln mutation in Factor V as a pathogenic risk factor for venous thrombosis. Thromb Haemostas 1995; 74: 139–48.Google Scholar
  130. 130.
    Sheppard DR. Activated protein C resistance: the most common risk factor for venous thromboembolism. J Am Board Fam Pract 2000; 13: 111–5.PubMedGoogle Scholar
  131. 131.
    De Stefano V, Martinelli I, Mannucci PM, Paciaroni K, Chiusolo P, Casorelli I, Rossi E, Leone G. The risk of recurrent deep venous thrombosis among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation. N Engl J Med 1999; 341: 801–6.PubMedGoogle Scholar
  132. 132.
    Vecchi M, Sacchi E, Saibeni S et al. Inflammatory bowel diseases are not associated with major hereditary conditions predisposing to thrombosis. Dig Dis Sci 2000; 45: 1465–9.PubMedGoogle Scholar
  133. 133.
    Zauber NP, Sabbath-Solitare M, Rajoria G, Mogan G. Factor V Leiden mutation is not increased in patients with inflammatory bowel disease. J Clin Gastroenterol 1998; 27: 215–6.PubMedGoogle Scholar
  134. 134.
    Levine A, Lahav J, Zahavi I, Raz A, Dinari G. Activated protein C resistance in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1998; 26: 172–4.PubMedGoogle Scholar
  135. 135.
    Haslam N, Standen GR, Probert CS. An investigation of the association of the factor V Leiden mutation and inflammatory bowel disease. Eur J Gastroenterol Hepatol 1999; 11: 1289–91.PubMedGoogle Scholar
  136. 136.
    Over HH, Ulgen S, Tuglular T et al. Thrombophilia and inflammatory bowel disease: does factor V mutation have a role? Eur J Gastroenterol Hepatol 1998; 10: 827–9.PubMedGoogle Scholar
  137. 137.
    Novacek G, Miehsler W, Kapiotis S, Katzenschlager R, Speiser W, Vogelsang H. Thromboembolism and resistance to activated protein C in patients with inflammatory bowel disease. Am J Gastroenterol 1999; 94: 685–90.PubMedGoogle Scholar
  138. 138.
    Liebman HA, Kashani N, Sutherland D, McGehee W, Kam AL. The factor V Leiden mutation increases the risk of venous thrombosis in patients with inflammatory bowel disease. Gastroenterology 1998; 115: 830–4.PubMedGoogle Scholar
  139. 139.
    Cattaneo M, Vecchi M, Zighetti ML, et al. High prevalence of hyperchomocysteinemia in patients with inflammatory bowel disease: a pathogenic link with thromboembolic complications? Thromb Haemostas 1998; 80: 542–5.Google Scholar
  140. 140.
    Mahmud N, Molloy A, McPartlin J et al. Increased prevalence of methylenetetrahydrofolate reductase C677T variant in patients with inflammatory bowel disease, and its clinical implications. Gut 1999; 45: 389–94.PubMedGoogle Scholar
  141. 141.
    Oldenburg B, Fijnheer R, van der Griend R, vanBerge-Henegouwen GP, Koningsberger JC. Homocysteine in inflammatory bowel disease: a risk factor for thromboembolic complications? Am J Gastroenterol 2000; 95: 2825–30.PubMedGoogle Scholar
  142. 142.
    Thompson N, Wakefield A, Pounder R. Inherited disorders of coagulation appear to protect against inflammatory bowel disease. Gastroenterology 1995; 108: 1011–15.PubMedGoogle Scholar
  143. 143.
    Kearon C, Gent M, Hirsh J et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism [published erratum appears in N Engl J Med 1999 22; 341:298]. N Engl J Med 1999; 340: 901–7.PubMedGoogle Scholar
  144. 144.
    Gaffney PR, Doyle CT, Gaffney A, Hogan J, Hayes DP, Annis P. Paradoxical response to heparin in 10 patients with ulcerative colitis. Am J Gastroenterol 1995; 90: 220–3.PubMedGoogle Scholar
  145. 145.
    Van Woert JH, Thompson RC, Cangemi JR, Metzger PP, Blackshear JL, Fleming CR. Streptokinase therapy for extensive venous thromboses in a patient with severe ulcerative colitis. Mayo Clin Proc 1990; 65: 1144–9.PubMedGoogle Scholar
  146. 146.
    Kermode AG, Ives FJ, Taylor B, Davis SJ, Carroll WM. Progressive dural venous sinus thrombosis treated with local streptokinase infusion [Letter]. J Neurol Neurosurg Psychiatry 1995; 58: 107–8.PubMedGoogle Scholar
  147. 147.
    Nguyen A. Prothrombin G20210A polymorphism and thrombophilia. Mayo Clin Proc 2000; 75: 595–604.PubMedGoogle Scholar
  148. 148.
    Muller S, Chesner IM, Sheridan J, Newman J. Ulcerative colitis complicated by disseminated intravascular coagulation. Postgrad Med J 1987; 63: 689–91.PubMedGoogle Scholar
  149. 149.
    Ryan FP, Timperley WR, Preston FE, Holdsworth CD. Cerebral involvement with disseminated intravascular coagulation in intestinal disease. J Clin Pathol 1977; 30: 551–5.PubMedGoogle Scholar
  150. 150.
    Wong TZ, Welch JP, Holt JB. Intraoperative disseminated intravascular coagulation in a patient with ulcerative colitis. Connect Med 1989; 53: 577–8.Google Scholar
  151. 151.
    Zlatanic J, Korelitz BI, Wisch N et al. Inflammatory bowel disease and immune thrombocytopenic purpura: is there a correlation? Am J Gastroenterol 1997; 92: 2285–8.PubMedGoogle Scholar
  152. 152.
    Mones RL. Thrombocytopenia and hypofibrinogenemia in association with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1983; 2: 175–7.PubMedGoogle Scholar
  153. 153.
    Gremse DA, Bancroft J, Moyer MS. Sulfasalazine hypersensitivity with hepatotoxicity, thrombocytopenia, and erythroid hypoplasia. J Pediatr Gastroenterol Nutr 1989; 9: 261–3.PubMedGoogle Scholar
  154. 154.
    Caprilli R, Corrao G, Taddei G, Tonelli F, Torchio P, Viscido A. Prognostic factors for postoperative recurrence of Crohn’s disease. Gruppo Italiano per lo Studio del Colon e del Retto (GISC). Dis Colon Rectum 1996; 39: 335–41.PubMedGoogle Scholar
  155. 155.
    Loftus EV, Jr., Tremaine WJ, Habermann TM, Harmsen WS, Zinsmeister AR, Sandborn WJ. Risk of lymphoma in inflammatory bowel disease. Am J Gastroenterol 2000; 95: 2308–12.PubMedGoogle Scholar
  156. 156.
    Connell WR, Kamm MA, Dickson M, Balkwill AM, Ritchie JK, Lennard-Jones JE. Long-term neoplasia risk after azathioprine treatment in inflammatory bowel disease. Lancet 1994; 343: 1249–52.PubMedGoogle Scholar
  157. 157.
    Caspi O, Polliack A, Klar R, Ben-Yehuda D. The association of inflammatory bowel disease and leukemia — coincidence or not? Leukemia Lymphoma 1995; 17: 255–62.PubMedGoogle Scholar
  158. 158.
    Georgescu L, Quinn GC, Schwartzman S, Paget SA. Lymphoma in patients with rheumatoid arthritis: association with the disease state or methotrexate treatment. Semin Arthritis Rheum 1997; 26: 794–804.PubMedGoogle Scholar
  159. 159.
    Greenstein AJ, Mullin GE, Strauchen JA et al. Lymphoma in inflammatory bowel disease. Cancer 1992; 69: 1119–23.PubMedGoogle Scholar
  160. 160.
    Palli D, Trallori G, Bagnoli S et al. Hodgkin’s disease risk is increased in patients with ulcerative colitis. Gastroenterology 2000; 119:647–53.PubMedGoogle Scholar
  161. 161.
    Korelitz BI, Mirsky FJ, Fleisher MR, Warman JI, Wisch N, Gleim GW. Malignant neoplasms subsequent to treatment of inflammatory bowel disease with 6-mercaptopurine. Am J Gastroenterol 1999; 94: 3248–53.PubMedGoogle Scholar
  162. 162.
    Present DH, Korelitz BI, Wisch N, Glass JL, Sachar DB, Pasternack BS. Treatment of Crohn’s disease with 6-mercaptopurine. A long-term, randomized, double-blind study. N Engl J Med 1980; 302: 981–7.PubMedGoogle Scholar
  163. 163.
    Present DH, Meltzer SJ, Krumholz MP, Wolke A, Korelitz BI. 6-Mercaptopurine in the management of inflammatory bowel disease: short-and long-term toxicity. Ann Intern Med 1989; 111:641–9.PubMedGoogle Scholar
  164. 164.
    Schabet M. Epidemiology of primary CNS lymphoma. J Neuro-Oncol 1999; 43: 199–201.Google Scholar
  165. 165.
    Lewis JD, Schwartz JS, Lichtenstein GR. Azathioprine for maintenance of remission in Crohn’s disease: benefits out weigh the risk of lymphoma. Gastroenterology 2000; 118: 1018–24.PubMedGoogle Scholar
  166. 166.
    Bo J, Schroder H, Kristinsson J et al. Possible carcinogenic effect of 6-mercaptopurine on bone marrow stem cells: relation to thiopurine metabolism. Cancer 1999; 86: 1080–6.PubMedGoogle Scholar
  167. 167.
    Kwong YL, Au WY, Liang RH. Acute myeloid leukemia after azathioprine treatment for autoimmune diseases: association with −7/7q. Cancer Genet Cytogenet 1998; 104: 94–7.PubMedGoogle Scholar
  168. 168.
    Heizer WD, Peterson JL. Acute myeloblastic leukemia following prolonged treatment of Crohn’s disease with 6-mercaptopurine. Dig Dis Sci 1998; 43: 1791–3.PubMedGoogle Scholar
  169. 169.
    DeMario MD, Liebowitz DN. Lymphomas in the immunocompromised patient. Semin Oncol 1998; 25: 492–502.PubMedGoogle Scholar
  170. 170.
    Nalesnik MA. Clinicopathologic features of posttransplant lymphoproliferative disorders. Ann Transplant 1997; 2: 33–40.PubMedGoogle Scholar
  171. 171.
    Kumar S, Fend F, Quintanilla-Martinez L et al. Epstein-Barr virus-positive primary gastrointestinal Hodgkin’s disease: association with inflammatory bowel disease and immunosuppression. Am J Surg Pathol 2000; 24: 66–73.PubMedGoogle Scholar
  172. 172.
    Calaminici MR, Sheaff MT, Norton AJ, Feakins RM. Ileocaecal Epstein-Barr virus-positive lymphoproliferative disorder complicating Crohn’s disease [Letter]. Histopathology 1999; 35: 388–90.PubMedGoogle Scholar
  173. 173.
    Larvol L, Soule JC, Le Tourneau A. Reversible lymphoma in the setting of azathioprine therapy for Crohn’s disease [Letter]. N Engl J Med 1994; 331: 883–4.PubMedGoogle Scholar
  174. 174.
    Bickston SJ, Lichtenstein GR, Arseneau KO, Cohen RB, Cominelli F. The relationship between infliximab treatment and lymphoma in Crohn’s disease. Gastroenterology 1999; 117:1433–7.PubMedGoogle Scholar
  175. 175.
    Pardi DS, Tremaine WJ, Sandborn WJ, McCarthy JT. Renal and urologic complications of inflammatory bowel disease. Am J Gastroenterol 1998; 93: 504–14.PubMedGoogle Scholar
  176. 176.
    Kahn E, Markowitz J, Simpser E, Aiges H, Daum F. Amyloidosis in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1989; 8: 447–53.PubMedGoogle Scholar
  177. 177.
    Lowdell CP, Shousha S, Parkins RA. The incidence of amyloidosis complicating inflammatory bowel disease. A prospective survey of 177 patients. Dis Colon Rectum 1986; 29: 351–4.PubMedGoogle Scholar
  178. 178.
    Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med 1997; 337: 898–909.PubMedGoogle Scholar
  179. 179.
    Gillmore JD, Hawkins PN, Pepys MB. Amyloidosis. A review of recent diagnostic and therapeutic developments. Br J Haematol 1997; 99: 245–56.PubMedGoogle Scholar
  180. 180.
    Lovat LB, Madhoo S, Pepys MB, Hawkins PN. Long-term survival in systemic amyloid A amyloidosis complicating Crohn’s disease. Gastroenterology 1997; 112: 1362–5.PubMedGoogle Scholar
  181. 181.
    Edwards P, Cooper DA, Turner J, O’Connor TJ, Byrnes DJ. Resolution of amyloidosis (AA type) complicating chronic ulcerative colitis. Gastroenterology 1988; 95: 810–15.PubMedGoogle Scholar
  182. 182.
    Gertz MA, Kyle RA. Secondary systemic amyloidosis: response and survival in 64 patients. Medicine 1991; 70: 246–56.PubMedGoogle Scholar
  183. 183.
    Fausa O, Nygaard K, Elgjo K. Amyloidosis and Crohn’s disease. Scand J Gastroenterol 1977; 12: 657–62.PubMedGoogle Scholar
  184. 184.
    Meyers S, Janowitz HD, Gumaste VV et al. Colchicinc therapy of the renal amyloidosis of ulcerative colitis. Gastroenterology 1988; 94: 1503–7.PubMedGoogle Scholar
  185. 185.
    Menges M, Steffen HM. Secondary amyloidosis in ulcerative colitis — successful treatment with colchicine. Z Gastroenterol 1996; 34: 753–6.PubMedGoogle Scholar
  186. 186.
    Gertz MA, Kyle RA. Amyloidosis: prognosis and treatment. Semin Arthritis Rheum 1994; 24: 124–38.PubMedGoogle Scholar
  187. 187.
    Ravid M, Shapira J, Kedar I, Feigl D. Regression of amyloidosis secondary to granulomatous ileitis following surgical resection and colchicine administration. Acta Hepato-Gastroenterol 1979; 26: 513–5.Google Scholar
  188. 188.
    Larvol L, Cervoni J, Besnier M, Dupouet L, Beaufils H, Clauvel J, Levecq H. Reversible nephrotic syndrome in Crohn’s disease complicated with renal amyloidosis. Gastroenterol Clin Biol 1998; 22: 639–41.PubMedGoogle Scholar
  189. 189.
    Horie Y, Chiba M, Miura K et al. Crohn’s disease associated with renal amyloidosis successfully treated with an elemental diet. J Gastroenterol 1997; 32: 663–7.PubMedGoogle Scholar
  190. 190.
    Mandelstam P, Simmons DE, Mitchell B. Regression of amyloid in Crohn’s disease after bowel resection. A 19-year follow-up. J Clin Gastroenterol 1989; 11: 324–6.PubMedGoogle Scholar
  191. 191.
    Iwakiri R, Sakemi T, Fujimoto K. Dimethylsulfoxide for renal dysfunction caused by systemic amyloidosis complicating Crohn’s disease [Letter; comment]. Gastroenterology 1999; 117: 1031–2.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Konstantinos A. Papadakis
    • 1
  • Maria T. Abreu
    • 2
  1. 1.Gastroenterology/IBD CenterCedars-Sinai Medical CenterLos AngelesUSA
  2. 2.Basic and Translational Research, IBD CenterCedars-Sinai Medical CenterLos AngelesUSA

Personalised recommendations