#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Idiopathic inflammatory bowel disease as a prothrombotic state


Authors: David Kamenář;  Julius Špičák
Authors‘ workplace: Klinika hepatogastroenterologie IKEM Praha
Published in: Vnitř Lék 2016; 62(5): 384-391
Category: Reviews

Overview

Prothrombotic states related to idiopathic bowel disease (IBD) are typically caused by abnormalities of hemostasis associated with inflammatory processes. The risk of thromboembolic complications in patients with IBD is approximately three times as high as in the general population. A critical role is played by the acquired risk factors including medication, while the proportion of inherited thrombophilia in patients with IBD is the same as in the general population. Many abnormalities can be identified through laboratory testing at the level of coagulation factors, fibrinolysis, thrombocytes and endothelium. Although there are no systematic guidelines for the prevention of thromboembolism in patients with IBD available, valid reasons for prophylactic administration of low-molecular-weight heparin are immobilization, hospitalization for IBD activity and surgery. The treatment of thromboembolism which complicates the course of IBD does not differ from its treatment among the general population, and concern over bleeding into gastrointestinal tract during anticoagulation should not outweigh the risk of possible fatal consequences of untreated thrombosis.

Key words:
idiopathic bowel inflammation – prothrombotic state – risk factors – thromboembolism – hereditary thrombophilia


Sources

1. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999; 340(6): 448–454. Erratum in N Engl J Med 1999; 340(17):1376.

2. McEver RP. Adhesive Interactions of Leukocytes, Platelets, and the Vessel Wall during Hemostasis and Inflammation. Thromb Haemost 2001; 86(3): 746–756.

3. Johnson K, Aarden L, Choi Y et al. The proinflammatory cytokine response to coagulation and endotoxin in whole blood. Blood 1996; 87(12): 5051–5060.

4. Stouthard JML, Levi M, Hack CE et al. Interleukin-6 stimulates coagulation, not fibrinolysis, in humans. Thromb Haemost 1996; 76(5): 738–742.

5. Levi M, van der Poll T, ten Cate H et al. The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia. Eur J Clin Invest 1997; 27(1): 3–9.

6. Devaraj S, Xu DY, Jialal I. C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis. Circulation 2003; 107(3): 398–404.

7. Murthy SK, Nguyen GC. Venous thromboembolism in inflammatory bowel disease: an epidemiological review. Am J Gastroenterol 2011; 106(4): 713–718.

8. Yuhara H, Steinmaus C, Corley D et al. Meta-analysis: the risk of venous thromboembolism in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2013; 37(10): 953–962.

9. Bernstein CN, Blanchard JF, Houston DS et al. The incidence of deep venous thrombosis and pulmonary embolism among patients with inflammatory bowel disease: a population-based cohort study. Thromb Haemost 2001; 85(3): 430–434.

10. Kappelman MD, Horvath-Puho E, Sandler RS et al. Thromboembolic risk among Danish children and adults with inflammatory bowel diseases: a population-based nationwide study. Gut 2011; 60(7): 937–943.

11. Miehsler W, Reinisch W, Valic E et al. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? Gut 2004; 53(4): 542–548.

12. Grip O, Svensson PJ, Lindgren S. Inflammatory bowel disease promotes venous thrombosis earlier in life. Scand J Gastroenterol 2000; 35(6): 619–623.

13. Novacek G, Weltermann A, Sobala A et al. Inflammatory bowel disease is a risk factor for recurrent venous thromboembolism. Gastroenterology 2010; 139(3): 779–787.

14. Bernstein CN, Nabalamba A. Hospitalization-based major comorbidity of inflammatory bowel disease in Canada. Can J Gastroenterol 2007; 21(8): 507–511.

15. Nguyen GC, Sam J. Rising prevalence of venous thromboembolism and its impact on mortality among hospitalized inflammatory bowel disease patients. Am J Gastroenterol 2008; 103(9): 2272–2280.

16. Merrill A, Millham F. Increased Risk of Postoperative Deep Vein Thrombosis and Pulmonary Embolism in Patients With Inflammatory Bowel Disease: A Study of National Surgical Quality Improvement Program Patients. Arch Surg 2012; 147(2): 120–124.

17. Nguyen GC, Boudreau H, Harris ML et al. Outcomes of Obstetric Hospitalizations Among Women With Inflammatory Bowel Disease in the United States. Clin Gastroenterol Hepatol 2009; 7(3): 329–334.

18. Bröms G, Granath F, Linder M et al. Complications from inflammatory bowel disease during pregnancy and delivery. Clin Gastroenterol Hepatol 2012; 10(11): 1246–1252.

19. Heit JA, Kobbervig CE, James AH et al. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 2005; 143(10): 697–706.

20. Grainge MJ, West J, Card TR. Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet 2010; 375(9715): 657–663.

21. Solem CA, Loftus EV, Tremaine WJ et al. Venous thromboembolism in inflammatory bowel disease. Am J Gastroenterol 2004; 99(1): 97–101.

22. Van Bodegraven AA, Schoorl M, Linskens RK et al. Persistent activation of coagulation and fibrinolysis after treatment of active ulcerative colitis. Eur J Gastroenterol Hepatol 2002; 14(4): 413–418.

23. Johns DR. Cerebrovascular complications of inflammatory bowel disease. Am J Gastroenterol 1991; 86(3): 367–370.

24. Keyser BJ, Hass AN. Retinal vascular disease in ulcerative colitis. Am J Ophthalmol 1994; 118(3): 395–396.

25. Hatoum OA, Spinelli KS, Abu-Hajir M et al. Mesenteric venous thrombosis in inflammatory bowel disease. J Clin Gastroenterol 2005; 39(1): 27–31.

26. Younes-Mhenni S, Derex L, Berruyer M et al. Large-artery stroke in a young patient with Crohn’s disease. Role of vitamin B6 deficiency-induced hyperhomocysteinemia. J Neurol Sci 2004; 221(1–2): 113–115.

27. Levy PJ, Tabares AH, Olin JW. Lower extremity arterial occlusions in young patients with Crohn’s colitis and premature atherosclerosis: report of six cases. Am J Gastroenterol 1997; 92(3): 494–497.

28. Di Fabio F, Obrand D, Satin R et al. Intra-abdominal venous and arterial thromboembolism in inflammatory bowel disease. Dis Colon Rectum 2009; 52(2): 336–342.

29. Mutlu B, Ermeydan CMH, Enç F et al. Acute myocardial infarction in a young woman with severe ulcerative colitis. Int J Cardiol 2002; 83(2): 183–185.

30. Zitomersky NL, Verhave M, Trenor CC. Thrombosis and inflammatory bowel disease: A call for improved awareness and prevention. Inflamm Bowel Dis 2011; 17(1): 458–470.

31. Jackson LM, O’Gorman PJ, O’Connell J et al. Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden. QJM 1997; 90(3): 183–188.

32. Esmon CT. The interactions between inflammation and coagulation. Br J Haematol 2005; 131(4): 417–430.

33. Lindmark E, Tenno T, Siegbahn A. Role of platelet P-selectin and CD40 ligand in the induction of monocytic tissue factor expression. Arterioscler Thromb Vasc Biol 2000; 20(10): 2322–2328.

34. Parry GC, Mackman N. NF-κB Mediated Transcription in Human Monocytic Cells and Endothelial Cells. Trends Cardiovasc Med 1998; 8(3): 138–142.

35. Chen Y, Wang J, Yao Y et al. CRP regulates the expression and activity of tissue factor as well as tissue factor pathway inhibitor via NF-kappaB and ERK 1/2 MAPK pathway. FEBS Lett 2009; 583(17): 2811–2818.

36. Chen C, Nan B, Lin P et al. C-reactive protein increases plasminogen activator inhibitor-1 expression in human endothelial cells. Thromb Res 2008; 122(1): 125–133.

37. Singh U, Devaraj S, Jialal I. C-reactive protein decreases tissue plasminogen activator activity in human aortic endothelial cells: evidence that C-reactive protein is a procoagulant. Arter Thromb Vasc Biol 2005; 25(10): 2216–2221.

38. Bisoendial RJ, Kastelein JJP, Levels JHM et al. Activation of inflammation and coagulation after infusion of C-reactive protein in humans. Circ Res 2005; 96(7): 714–716.

39. Hein TW, Singh U, Vasquez-Vivar J et al. Human C-reactive protein induces endothelial dysfunction and uncoupling of eNOS in vivo. Atherosclerosis 2009; 206(1): 61–68.

40. Hudson M, Chitolie A, Hutton RA et al. Thrombotic vascular risk factors in inflammatory bowel disease. Gut 1996; 38(5): 733–737.

41. Kume K, Yamasaki M, Tashiro M et al. Activations of coagulation and fibrinolysis secondary to bowel inflammation in patients with ulcerative colitis. Intern Med 2007; 46(17): 1323–1329.

42. Zezos P, Papaioannou G, Nikolaidis N et al. Elevated plasma von Willebrand factor levels in patients with active ulcerative colitis reflect endothelial perturbation due to systemic inflammation. World J Gastroenterol 2005; 11(48): 7639–7345.

43. Smith CJ, Haire WD, Kaufman SS et al. Determination of prothrombin activation fragments in young patients with inflammatory bowel disease. Am J Gastroenterol 1996; 91(6): 1221–1225.

44. 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(12): 1183–1188.

45. Chiarantini E, Valanzano R, Liotta AA et al. Hemostatic abnormalities in inflammatory bowel disease. Thromb Res 1996; 82(2): 137–146.

46. Souto JC, Martínez 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(9): 1883–1889.

47. Saibeni S, Vecchi M, Valsecchi C et al. Reduced free protein S levels in patients with inflammatory bowel disease: Prevalence, clinical relevance, and role of anti-protein S antibodies. Dig Dis Sci 2001; 46(3): 637–643.

48. 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(1): 190–194.

49. Faioni EM, Ferrero S, Fontana G et al. Expression of endothelial protein C receptor and thrombomodulin in the intestinal tissue of patients with inflammatory bowel disease. Crit Care Med 2004; 32(5 Suppl): S266-S270.

50. Lorenz R, Olbert P, Born P. Factor XIII in chronic inflammatory bowel diseases. Semin Thromb Hemost 1996; 22(5): 451–455.

51. Andoh A, Tsujikawa T, Hata K et al. Elevated circulating platelet-derived microparticles in patients with active inflammatory bowel disease. Am J Gastroenterol 2005; 100(9): 2042–2048.

52. Saibeni S, Bottasso B, Spina L et al. Assessment of thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels in inflammatory bowel diseases. Am J Gastroenterol 2004; 99(10): 1966–1970.

53. Heits F, Stahl M, Ludwig D et al. Elevated serum thrombopoietin and interleukin-6 concentrations in thrombocytosis associated with inflammatory bowel disease. J Interferon Cytokine Res 1999; 19(7): 757–760.

54. Collins CE, Rampton DS, Rogers J et al. Platelet aggregation and neutrophil sequestration in the mesenteric circulation in inflammatory bowel disease. Eur J Gastroenterol Hepatol 1997; 9(12): 1213–1217.

55. Collins CE, Cahill MR, Newland AC et al. Platelets circulate in an activated state in inflammatory bowel disease. Gastroenterology 1994; 106(4): 840–845.

56. Danese S, Katz JA, Saibeni S et al. Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients. Gut 2003; 52(10): 1435–1441.

57. Menchén L, Marín-Jiménez I, Arias-Salgado EG et al. Matrix metalloproteinase 9 is involved in Crohn’s disease-associated platelet hyperactivation through the release of soluble CD40 ligand. Gut 2009; 58(7): 920–928.

58. Sawada-Hase N, Kiyohara T, Miyagawa J et al. An increased number of CD40-high monocytes in patients with Crohn’s disease. Am J Gastroenterol 2000; 95(6): 1516–1523.

59. Power CA, Clemetson JM, Clemetson KJ et al. Chemokine and chemokine receptor mRNA expression in human platelets. Cytokine 1995; 7(6): 479–482.

60. Irving PM, Macey MG, Shah U et al. Formation of platelet-leukocyte aggregates in inflammatory bowel disease. Inflamm Bowel Dis 2004; 10(4): 361–372.

61. Boehme MW, Autschbach F, Zuna I et al. Elevated serum levels and reduced immunohistochemical expression of thrombomodulin in active ulcerative colitis. Gastroenterology 1997; 113(1): 107–117.

62. Meucci G, Pareti F, Vecchi M et al. Serum von Willebrand factor levels in patients with inflammatory bowel disease are related to systemic inflammation. Scand J Gastroenterol 1999; 34(3): 287–290.

63. Papa A, Scaldaferri F, Danese S et al. Vascular involvement in inflammatory bowel disease: pathogenesis and clinical aspects. Dig Dis 2008; 26(2): 149–155.

64. Hatoum OA, Binion DG, Otterson MF et al. Acquired microvascular dysfunction in inflammatory bowel disease: Loss of nitric oxide-mediated vasodilation. Gastroenterology 2003; 125(1): 58–69.

65. Horowitz S, Binion DG, Nelson VM et al. Increased arginase activity and endothelial dysfunction in human inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 2007; 292(5): G1323-G1336.

66. Lancellotti S, De Filippis V, Pozzi N et al. Formation of methionine sulfoxide by peroxynitrite at position 1606 of von Willebrand factor inhibits its cleavage by ADAMTS-13: A new prothrombotic mechanism in diseases associated with oxidative stress. Free Radic Biol Med 2010; 48(3): 446–456.

67. Owczarek D, Cibor D, Mach T. Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine, and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) level in patients with inflammatory bowel diseases. Inflamm Bowel Dis 2010; 16(1): 52–57.

68. Van De Wouwer M, Collen D, Conway EM. Thrombomodulin-protein C-EPCR system integrated to regulate coagulation and inflammation. Arterioscler Thromb Vasc Biol 2004; 24(8): 1374–1383.

69. Dahlbäck B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood 2008; 112(1): 19–27.

70. Guédon C, Le Cam-Duche V, Lalaude O et al. Prothrombotic inherited abnormalities other than factor V Leiden mutation do not play a role in venous thrombosis in inflammatory bowel disease. Am J Gastroenterol 2001; 96(5): 1448–1454.

71. Koutroubakis IE, Sfiridaki A, Tsiolakidou G et al. Genetic risk factors in patients with inflammatory bowel disease and vascular complications: case-control study. Inflamm Bowel Dis 2007; 13(4): 410–415.

72. Bernstein CN, Sargent M, Vos HL et al. Mutations in clotting factors and inflammatory bowel disease. Am J Gastroenterol 2007; 102(2): 338–343.

73. Liebman HA, Kashani N, Sutherland D et al. The factor V Leiden mutation increases the risk of venous thrombosis in patients with inflammatory bowel disease. Gastroenterology 1998; 115(4): 830–834.

74. Zhong M, Dong XW, Zheng Q et al. Factor v Leiden and thrombosis in patients with inflammatory bowel disease (IBD): A meta-analysis. Thromb Res 2011; 128(5): 403–409.

75. Liang J, Wu S, Feng B et al. Factor V Leiden and inflammatory bowel disease: a systematic review and meta-analysis. J Gastroenterol 2011; 46(10): 1158–1166.

76. 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(7): 1465–1469.

77. Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: A meta-analysis of published epidemiological studies. J Thromb Haemost 2005; 3(2): 292–299.

78. Dawson S, Hamsten A, Wiman B et al. Genetic variation at the plasminogen activator inhibitor-1 locus is associated with altered levels of plasma plasminogen activator inhibitor-1 activity. Arterioscler Thromb 1991; 11(1): 183–190.

79. Stegnar M, Uhrin P, Peternel P et al. The 4G/5G sequence polymorphism in the promoter of plasminogen activator inhibitor-1 (PAI-1) gene: Relationship to plasma PAI-1 level in venous thromboembolism. Thromb Haemost 1998; 79(5): 975–979.

80. Heliö T, Wartiovaara U, Halme L et al. Arg506Gln factor V mutation and Val34Leu factor XIII polymorphism in Finnish patients with inflammatory bowel disease. Scand J Gastroenterol 1999; 34(2): 170–174.

81. Yurekli BPS, Aksoy DY, Aybar M et al. The search for a common thrombophilic state during the active state of inflammatory bowel disease. J Clin Gastroenterol 2006; 40(9): 809–813.

82. Humphrey LL, Fu R, Rogers K et al. Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis. Mayo Clin Proc 2008; 83(11): 1203–1212.

83. den Heijer M, Rosendaal FR, Blom HJ et al. Hyperhomocysteinemia and venous thrombosis: A meta-analysis. Thromb Haemost 1998; 80(6): 874–877.

84. Oussalah A, Guéant JL, Peyrin-Biroulet L. Meta-analysis: Hyperhomocysteinaemia in inflammatory bowel diseases. Aliment Pharmacol Ther 2011; 34(10): 1173–1184.

85. 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(11): 2507–2512.

86. Saibeni S, Ciscato C, Vecchi M et al. Antibodies to tissue-type plasminogen activator (t-PA) in patients with inflammatory bowel disease: high prevalence, interactions with functional domains of t-PA and possible implications in thrombosis. J Thromb Haemost 2006; 4(7): 1510–1516.

87. Carty E, MacEy M, Rampton DS. Inhibition of platelet activation by 5-aminosalicylic acid in inflammatory bowel disease. Aliment Pharmacol Ther 2000; 14(9): 1169–1179.

88. Fägerstam JP, Whiss PA, Ström M et al. Expression of platelet P-selectin and detection of soluble P-selectin, NPY and RANTES in patients with inflammatory bowel disease. Inflamm Res 2000; 49(9): 466–472.

89. Johannesdottir SA, Horváth-Puhó E, Dekkers OM et al. Use of Glucocorticoids and Risk of Venous Thromboembolism: A Nationwide Population-Based Case-Control Study. JAMA Intern Med 2013; 173(9): 743–752.

90. Małyszko J, Małyszko JS, Takada A et al. Effects of immunosuppressive drugs on platelet aggregation in vitro. Ann Transplant 2002; 7(1): 55–68.

91. Hommes DW, van Dullemen HM, Levi M et al. Beneficial effect of treatment with a monoclonal anti-tumor necrosis factor-alpha antibody on markers of coagulation and fibrinolysis in patients with active Crohn’s disease. Haemostasis 1997; 27(6): 269–277.

92. Danese S, Sans M, Scaldaferri F et al. TNF-alpha blockade down-regulates the CD40/CD40L pathway in the mucosal microcirculation: a novel anti-inflammatory mechanism of infliximab in Crohn’s disease. J Immunol 2006; 176(4): 2617–2624.

93. Chamouard P, Desprez D, Hugel B et al. Circulating cell-derived microparticles in Crohn’s disease. Dig Dis Sci 2005; 50(3): 574–580.

94. Vereckei E, Krivan G, Reti M et al. Anti-TNF-alpha-induced anti-phospholipid syndrome manifested as necrotizing vasculitis. Scand J Rheumatol 2010; 39(2): 175–177.

95. Davies R, Galloway JB, Watson KD et al. Venous thrombotic events are not increased in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis 2011; 70(10): 1831–1834.

96. Lorenz R, Born P, Olbert P et al. Factor XIII substitution in ulcerative colitis. Lancet 1995; 345(8947): 449–450.

97. Oshitani N, Nakamura S, Matsumoto T et al. Treatment of Crohn’s disease fistulas with coagulation factor XIII. Lancet 1996; 347(8994): 119–120.

98. Bregenzer N, Caesar I, Andus T et al. Lack of clinical efficacy of additional factor XIII treatment in patients with steroid refractory colitis. The Factor XIII Study Group. Z Gastroenterol 1999; 37(10): 999–1004.

99. Shen J, Ran ZH, Tong JL et al. Meta-analysis: The utility and safety of heparin in the treatment of active ulcerative colitis. Aliment Pharmacol Ther 2007; 26(5): 653–663.

100. Chande N, McDonald JW, MacDonald JK et al. Unfractionated or low-molecular weight heparin for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2010; (10): CD006774. Dostupné z DOI: <http://dx.doi.org/10.1002/14651858.CD006774.pub3>.

101. Huerta C, Johansson S, Wallander MA et al. Risk factors and short-term mortality of venous thromboembolism diagnosed in the primary care setting in the United Kingdom. Arch Intern Med 2007; 167(9): 935–943.

102. van der Woude CJ, Kolacek S, Dotan I et al. European evidenced-based consensus on reproduction in inflammatory bowel disease. J Crohns Colitis 2010; 4(5): 493–510.

103. Kvasnička J. Primární antitrombotická prevence žilní trombózy ve vnitřním lékařství. Vnitř Lék 2005; 51(7–8): 781–789.

104. Kornbluth A, Sachar DB Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 2010; 105(3): 501–523. Erratum in Am J Gastroenterol 2010; 105(3): 500.

105. Mowat C, Cole A, Windsor A et al. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011; 60(5): 571–607.

106. Van Assche G, Dignass A, Reinisch W et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: Special situations. J Crohns Colitis 2010; 4(1): 63–101.

107. Van Assche G, Dignass A, Bokemeyer B et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: special situations. J Crohns Colitis 2013; 7(1): 1–33.

108. Leizorovicz A, Cohen AT, Turpie AG et al. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004; 110(7): 874–879.

109. Samama MM, Cohen AT, Darmon JY et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med 1999; 341(11): 793–800.

110. Aryal K, Al-Khaffaf H. Venous thromboembolic complications following air travel: what’s the quantitative risk? A literature review. Eur J Vasc Endovasc Surg 2006; 31(2): 187–199.

111. Tinsley A, Naymagon S, Trindade AJ et al. A survey of current practice of venous thromboembolism prophylaxis in hospitalized inflammatory bowel disease patients in the United States. J Clin Gastroenterol 2013; 47(1): e1-e6. Dostupné z DOI: <http://dx.doi.org/10.1097/MCG.0b013e31824c0dea>.

112. Koutroubakis IE. Therapy insight: Vascular complications in patients with inflammatory bowel disease. Nat Clin Pract Gastroenterol Hepatol 2005; 2(6): 266–272.

113. Qaseem A, Snow V, Barry P et al. Current diagnosis of venous thromboembolism in primary care: A clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Fam Med 2007; 5(1): 57–62.

114. Torbicki A, Perrier A, Konstantinides S et al. Guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2008; 29(18): 2276–2315.

115. Tan VP, Chung A, Yan BP et al. Venous and arterial disease in inflammatory bowel disease. J Gastroenterol Hepatol 2013; 28(7): 1095–1113.

Labels
Diabetology Endocrinology Internal medicine
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#