Risk of Venous Thromboembolism in Patients with Inflammatory Bowel Disease

 

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Abstract

There is ample evidence of an increased risk of venous thromboembolism (VTE) in inflammatory bowel disease (IBD). Recent large studies have quantified this risk showing that IBD patients run a 1.5 to 3.6 higher risk of developing VTE than healthy controls. The development of VTE in IBD seems to be multifactorial, resulting from multiple interactions between acquired and inherited risk factors. The most important independent acquired risk factors include disease activity, hospitalization, colonic localization, and recent surgery. The main genetic defects that have been established as risk factors for VTE in the general population are rather uncommon in IBD, but when present, they increase the risk of VTE. IBD has been demonstrated to represent an independent risk factor for the recurrence of VTE. An increased risk of VTE-related mortality when compared with non-IBD patients has been reported. The guidelines for diagnosis and treatment of IBD patients with VTE are similar to that of thrombotic non-IBD patients. There is a consensus on the use of thromboprophylaxis mainly in hospitalized IBD patients with acute flares, but the prevention strategies need further evaluation in future studies.

• References

• 1 Talbot RW, Heppell J, Dozois RR, Beart Jr RW. Vascular complications of inflammatory bowel disease. Mayo Clin Proc 1986; 61 (2) 140-145
  CrossrefPubMedGoogle Scholar
• 2 Bernstein CN, Blanchard JF, Houston DS, Wajda A. 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
  PubMedGoogle Scholar
• 3 Solem CA, Loftus EV, Tremaine WJ, Sandborn WJ. Venous thromboembolism in inflammatory bowel disease. Am J Gastroenterol 2004; 99 (1) 97-101
  CrossrefPubMedGoogle Scholar
• 4 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
  CrossrefPubMedGoogle Scholar
• 5 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
  CrossrefPubMedGoogle Scholar
• 6 Koutroubakis IE. Therapy insight: Vascular complications in patients with inflammatory bowel disease. Nat Clin Pract Gastroenterol Hepatol 2005; 2 (6) 266-272
  CrossrefPubMedGoogle Scholar
• 7 Ha C, Magowan S, Accortt NA, Chen J, Stone CD. Risk of arterial thrombotic events in inflammatory bowel disease. Am J Gastroenterol 2009; 104 (6) 1445-1451
  CrossrefPubMedGoogle Scholar
• 8 Bernstein CN, Wajda A, Blanchard JF. The incidence of arterial thromboembolic diseases in inflammatory bowel disease: a population-based study. Clin Gastroenterol Hepatol 2008; 6 (1) 41-45
  Google Scholar
• 9 Danese S, Papa A, Saibeni S, Repici A, Malesci A, Vecchi M. Inflammation and coagulation in inflammatory bowel disease: The clot thickens. Am J Gastroenterol 2007; 102 (1) 174-186
  CrossrefPubMedGoogle Scholar
• 10 Huerta C, Johansson S, Wallander MA, García Rodríguez LA. 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
  CrossrefPubMedGoogle Scholar
• 11 Hippisley-Cox J, Coupland C. Development and validation of risk prediction algorithm (Q Thrombosis) to estimate future risk of venous thromboembolism: prospective cohort study. BMJ 2011; 343: d4656
  CrossrefPubMedGoogle Scholar
• 12 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
  CrossrefPubMedGoogle Scholar
• 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 , e1
  CrossrefPubMedGoogle Scholar
• 14 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
  CrossrefPubMedGoogle Scholar
• 15 Zöller B, Li X, Sundquist J, Sundquist K. Risk of pulmonary embolism in patients with autoimmune disorders: a nationwide follow-up study from Sweden. Lancet 2012; 379 (9812) 244-249
  CrossrefPubMedGoogle Scholar
• 16 Lazzerini M, Bramuzzo M, Maschio M, Martelossi S, Ventura A. Thromboembolism in pediatric inflammatory bowel disease: systematic review. Inflamm Bowel Dis 2011; 17 (10) 2174-2183
  CrossrefPubMedGoogle Scholar
• 17 Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet 2012; 379 (9828) 1835-1846
  CrossrefPubMedGoogle Scholar
• 18 Koutroubakis IE. Venous thromboembolism in hospitalized inflammatory bowel disease patients: the magnitude of the problem is staggering. Am J Gastroenterol 2008; 103 (9) 2281-2283
  CrossrefPubMedGoogle Scholar
• 19 Wallaert JB, De Martino RR, Marsicovetere PS , et al. Venous thromboembolism after surgery for inflammatory bowel disease: are there modifiable risk factors? Data from ACS NSQIP. Dis Colon Rectum 2012; 55 (11) 1138-1144
  CrossrefPubMedGoogle Scholar
• 20 Winther K, Bondesen S, Hansen SH, Hvidberg EF. Lack of effect of 5-aminosalicylic acid on platelet aggregation and fibrinolytic activity in vivo and in vitro. Eur J Clin Pharmacol 1987; 33 (4) 419-422
  CrossrefPubMedGoogle Scholar
• 21 Stassen PM, Derks RP, Kallenberg CG, Stegeman CA. Venous thromboembolism in ANCA-associated vasculitis—incidence and risk factors. Rheumatology (Oxford) 2008; 47 (4) 530-534
  CrossrefPubMedGoogle Scholar
• 22 Koutroubakis IE, Pena AS. Disease activity and venous thromboembolism in inflammatory bowel disease. Lancet 2010; 375 (9727) 1689 , author reply 1690–1691
  CrossrefPubMedGoogle Scholar
• 23 Ingegnoli F, Fantini F, Favalli EG , et al. Inflammatory and prothrombotic biomarkers in patients with rheumatoid arthritis: effects of tumor necrosis factor-alpha blockade. J Autoimmun 2008; 31 (2) 175-179
  CrossrefPubMedGoogle Scholar
• 24 Oussalah A, Guéant JL, Peyrin-Biroulet L. Meta-analysis: hyperhomocysteinaemia in inflammatory bowel diseases. Aliment Pharmacol Ther 2011; 34 (10) 1173-1184
  CrossrefPubMedGoogle Scholar
• 25 Di Fabio F, Lykoudis P, Gordon PH. Thromboembolism in inflammatory bowel disease: an insidious association requiring a high degree of vigilance. Semin Thromb Hemost 2011; 37 (3) 220-225
  Article in Thieme ConnectPubMedGoogle Scholar
• 26 Germain M, Saut N, Greliche N , et al. Genetics of venous thrombosis: insights from a new genome wide association study. PLoS ONE 2011; 6 (9) e25581
  CrossrefPubMedGoogle Scholar
• 27 Dahlbäck B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood 2008; 112 (1) 19-27
  CrossrefPubMedGoogle Scholar
• 28 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
  CrossrefPubMedGoogle Scholar
• 29 Bernstein CN, Sargent M, Vos HL, Rosendaal FR. Mutations in clotting factors and inflammatory bowel disease. Am J Gastroenterol 2007; 102 (2) 338-343
  CrossrefPubMedGoogle Scholar
• 30 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
  CrossrefPubMedGoogle Scholar
• 31 Guédon C, Le Cam-Duchez V, Lalaude O, Ménard JF, Lerebours E, Borg JY. 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
  CrossrefPubMedGoogle Scholar
• 32 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
  CrossrefPubMedGoogle Scholar
• 33 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
  CrossrefPubMedGoogle Scholar
• 34 Zhong M, Dong XW, Zheng Q, Tong JL, Ran ZH. Factor V Leiden and thrombosis in patients with inflammatory bowel disease (IBD): a meta-analysis. Thromb Res 2011; 128: 403-409
  CrossrefPubMedGoogle Scholar
• 35 Tsiolakidou G, Koutroubakis IE. Thrombosis and inflammatory bowel disease-the role of genetic risk factors. World J Gastroenterol 2008; 14 (28) 4440-4444
  CrossrefPubMedGoogle Scholar
• 36 Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88 (10) 3698-3703
  CrossrefPubMedGoogle Scholar
• 37 Spina L, Saibeni S, Battaglioli T, Peyvandi F, de Franchis R, Vecchi M. Thrombosis in inflammatory bowel diseases: role of inherited thrombophilia. Am J Gastroenterol 2005; 100 (9) 2036-2041
  CrossrefPubMedGoogle Scholar
• 38 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
  CrossrefPubMedGoogle Scholar
• 39 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 (3) 389-394
  CrossrefPubMedGoogle Scholar
• 40 Danese S, Papa A. PAI-1 and TAFI in inflammatory bowel disease: the yin and yang of the fibrinolytic system. Eur J Gastroenterol Hepatol 2008; 20 (9) 826-828
  CrossrefPubMedGoogle Scholar
• 41 Koutroubakis IE, Sfiridaki A, Tsiolakidou G, Coucoutsi C, Theodoropoulou A, Kouroumalis EA. Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 levels in inflammatory bowel disease. Eur J Gastroenterol Hepatol 2008; 20 (9) 912-916
  CrossrefPubMedGoogle Scholar
• 42 Karimi O, Crusius JB, Coucoutsi C , et al. JAK2 V617F mutation is not involved in thromboembolism in IBD. Inflamm Bowel Dis 2008; 14 (11) 1606-1607
  CrossrefPubMedGoogle Scholar
• 43 Roy PM, Meyer G, Vielle B , et al; EMDEPU Study Group. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism. Ann Intern Med 2006; 144 (3) 157-164
  CrossrefPubMedGoogle Scholar
• 44 Ceriani E, Combescure C, Le Gal G , et al. Clinical prediction rules for pulmonary embolism: a systematic review and meta-analysis. J Thromb Haemost 2010; 8 (5) 957-970
  PubMedGoogle Scholar
• 45 Aujesky D, Roy PM, Verschuren F , et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet 2011; 378 (9785) 41-48
  CrossrefPubMedGoogle Scholar
• 46 Geerts WH, Bergquist D, Pineo GF , et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based. Clinical Practice Guidelines (8th Edition). Chest 2008; 133: 381S-453S
  CrossrefPubMedGoogle Scholar
• 47 Kornbluth A, Sachar DB. Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 2010; 105 (3) 501-523 , quiz 524
  CrossrefPubMedGoogle Scholar
• 48 Tinsley A, Naymagon S, Trindade AJ, Sachar DB, Sands BE, Ullman TA. 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
  CrossrefPubMedGoogle Scholar
• 49 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: 63-101
  CrossrefPubMedGoogle Scholar
• 50 Zitomersky NL, Verhave M, Trenor III CC. Thrombosis and inflammatory bowel disease: a call for improved awareness and prevention. Inflamm Bowel Dis 2011; 17 (1) 458-470
  CrossrefPubMedGoogle Scholar