Download PDF
Semin Thromb Hemost 2011; 37(3): 220-225
DOI: 10.1055/s-0031-1273086
© Thieme Medical Publishers

Thromboembolism in Inflammatory Bowel Disease: An Insidious Association Requiring a High Degree of Vigilance

Francesco Di Fabio1 , Pavlos Lykoudis1 , Philip H. Gordon2
  • 1Division of Surgery, Southampton General Hospital, Southampton University Hospitals NHS Trust, Southampton, United Kingdom
  • 2Colon & Rectal Surgery, Sir Mortimer B. Davis – Jewish General Hospital, McGill University, Montreal, Quebec, Canada
Further Information

Publication History

Publication Date:
31 March 2011 (online)

    Permissions and Reprints

ABSTRACT

Venous and arterial thromboembolism are both serious extraintestinal manifestations of inflammatory bowel disease (IBD). Acquired risk factors seem to play a more prominent role than congenital in promoting thrombotic events. Prevention of thromboembolism is thus mainly aimed at minimizing the acquired/reversible risk factors (e.g., inflammation, immobility, hospitalization, steroid therapy, central intravenous catheters, smoking, oral contraceptives, and deficiency of B vitamins and folate). The diagnosis of venous and arterial thromboembolism is extremely challenging and requires a high degree of vigilance. Deep vein thrombosis and pulmonary embolism may be clinically silent or manifest with only few specific symptoms. Thrombosis of the portal vein system may occur with nonspecific symptoms such as abdominal pain, nausea/vomiting, abdominal tenderness, ascites, and fever. The diagnosis of arterial thromboembolism may also be challenging, particularly when the splanchnic region is involved. Indeed, arterial thrombosis of the splanchnic region tends to be overlooked and misinterpreted as a clinical exacerbation of IBD. Early diagnosis plays a central role in optimizing the therapeutic intervention and reducing the risk of short-term and long-term thrombosis-associated complications. The decision regarding the duration of systemic anticoagulation must take into account the individual risk of intestinal bleeding.

KEYWORDS

Inflammatory bowel disease - arterial thromboembolism - venous thromboembolism - heparin.

REFERENCES

  • 1 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
    CrossrefPubMedSearch in Google Scholar
  • 2 Quera R, Shanahan F. Thromboembolism—an important manifestation of inflammatory bowel disease.  Am J Gastroenterol. 2004;  99 (10) 1971-1973
    CrossrefPubMedSearch in Google Scholar
  • 3 Koutroubakis I E. Venous thromboembolism in hospitalized inflammatory bowel disease patients: the magnitude of the problem is staggering.  Am J Gastroenterol. 2008;  103 (9) 2281-2283
    CrossrefPubMedSearch in Google Scholar
  • 4 Bernstein C N, Blanchard J F, Houston D S, 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
    PubMedSearch in Google Scholar
  • 5 Nguyen G C, 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
    CrossrefPubMedSearch in Google Scholar
  • 6 Nguyen G C, Boudreau H, Harris M L, Maxwell C V. Outcomes of obstetric hospitalizations among women with inflammatory bowel disease in the United States.  Clin Gastroenterol Hepatol. 2009;  7 (3) 329-334
    CrossrefPubMedSearch in Google Scholar
  • 7 Ha C, Magowan S, Accortt N A, Chen J, Stone C D. Risk of arterial thrombotic events in inflammatory bowel disease.  Am J Gastroenterol. 2009;  104 (6) 1445-1451
    CrossrefPubMedSearch in Google Scholar
  • 8 Bernstein C N, Wajda A, Blanchard J F. The incidence of arterial thromboembolic diseases in inflammatory bowel disease: a population-based study.  Clin Gastroenterol Hepatol. 2008;  6 (1) 41-45
    Search in 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
    CrossrefPubMedSearch in Google Scholar
  • 10 Talbot R W, Heppell J, Dozois R R, Beart Jr R W. Vascular complications of inflammatory bowel disease.  Mayo Clin Proc. 1986;  61 (2) 140-145
    CrossrefPubMedSearch in Google Scholar
  • 11 Solem C A, Loftus E V, Tremaine W J, Sandborn W J. Venous thromboembolism in inflammatory bowel disease.  Am J Gastroenterol. 2004;  99 (1) 97-101
    CrossrefPubMedSearch in Google Scholar
  • 12 Jackson L M, O'Gorman P J, O'Connell J, Cronin C C, Cotter K P, Shanahan F. Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden.  QJM. 1997;  90 (3) 183-188
    CrossrefPubMedSearch in Google Scholar
  • 13 Webberley M J, Hart M T, Melikian V. Thromboembolism in inflammatory bowel disease: role of platelets.  Gut. 1993;  34 (2) 247-251
    CrossrefPubMedSearch in Google Scholar
  • 14 Hudson M, Chitolie A, Hutton R A, Smith M S, Pounder R E, Wakefield A J. Thrombotic vascular risk factors in inflammatory bowel disease.  Gut. 1996;  38 (5) 733-737
    CrossrefPubMedSearch in Google Scholar
  • 15 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
    CrossrefPubMedSearch in Google Scholar
  • 16 Oldenburg B, Fijnheer R, van der Griend R, vanBerge-Henegouwen G P, Koningsberger J C. Homocysteine in inflammatory bowel disease: a risk factor for thromboembolic complications?.  Am J Gastroenterol. 2000;  95 (10) 2825-2830
    CrossrefPubMedSearch in Google Scholar
  • 17 Oldenburg B, Van Tuyl B A, van der Griend R, Fijnheer R, van Berge Henegouwen G P. Risk factors for thromboembolic complications in inflammatory bowel disease: the role of hyperhomocysteinaemia.  Dig Dis Sci. 2005;  50 (2) 235-240
    CrossrefPubMedSearch in Google Scholar
  • 18 Grip O, Svensson P J, Lindgren S. Inflammatory bowel disease promotes venous thrombosis earlier in life.  Scand J Gastroenterol. 2000;  35 (6) 619-623
    CrossrefPubMedSearch in Google Scholar
  • 19 Wong T, Nightingale J, Winter M, Muller A F. Spontaneous venous thrombosis in inflammatory bowel disease: relevance of factor V Leiden and the prothrombin gene mutation.  J Thromb Haemost. 2003;  1 (6) 1326-1328
    CrossrefPubMedSearch in Google Scholar
  • 20 Koutroubakis I E. Therapy insight: vascular complications in patients with inflammatory bowel disease.  Nat Clin Pract Gastroenterol Hepatol. 2005;  2 (6) 266-272
    CrossrefPubMedSearch in Google Scholar
  • 21 Koutroubakis I E, 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
    CrossrefPubMedSearch in Google Scholar
  • 22 Papa A, Danese S, Grillo A, Gasbarrini G, Gasbarrini A. Review article: inherited thrombophilia in inflammatory bowel disease.  Am J Gastroenterol. 2003;  98 (6) 1247-1251
    CrossrefPubMedSearch in Google Scholar
  • 23 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
    CrossrefPubMedSearch in Google Scholar
  • 24 Guédon C, Le Cam-Duchez V, Lalaude O, Ménard J F, Lerebours E, Borg J Y. 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
    PubMedSearch in Google Scholar
  • 25 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
    CrossrefPubMedSearch in Google Scholar
  • 26 Saibeni S, Saladino V, Chantarangkul V et al.. Increased thrombin generation in inflammatory bowel diseases.  Thromb Res. 2010;  125 (3) 278-282
    CrossrefPubMedSearch in Google Scholar
  • 27 Lichtman M A, Beutler E, Kaushansky K, Kipps T J, Seligsohn U, Prchal J eds.. Williams Hematology. 7th ed. New York, NY: McGraw-Hill Professional; 2005
    Search in Google Scholar
  • 28 Umit H, Asil T, Celik Y et al.. Cerebral sinus thrombosis in patients with inflammatory bowel disease: a case report.  World J Gastroenterol. 2005;  11 (34) 5404-5407
    PubMedSearch in Google Scholar
  • 29 Tsujikawa T, Urabe M, Bamba H et al.. Haemorrhagic cerebral sinus thrombosis associated with ulcerative colitis: a case report of successful treatment by anticoagulant therapy.  J Gastroenterol Hepatol. 2000;  15 (6) 688-692
    CrossrefPubMedSearch in Google Scholar
  • 30 Johns D R. Cerebrovascular complications of inflammatory bowel disease.  Am J Gastroenterol. 1991;  86 (3) 367-370
    PubMedSearch in Google Scholar
  • 31 Doi M, Nakaseko Y, Uji Y, Fujioka C. Central retinal vein occlusion during remission of ulcerative colitis.  Jpn J Ophthalmol. 1999;  43 (3) 213-216
    CrossrefPubMedSearch in Google Scholar
  • 32 Keyser B J, Hass A N. Retinal vascular disease in ulcerative colitis.  Am J Ophthalmol. 1994;  118 (3) 395-396
    PubMedSearch in Google Scholar
  • 33 Ruby A J, Jampol L M. Crohn's disease and retinal vascular disease.  Am J Ophthalmol. 1990;  110 (4) 349-353
    PubMedSearch in Google Scholar
  • 34 Schneiderman J H, Sharpe J A, Sutton D M. Cerebral and retinal vascular complications of inflammatory bowel disease.  Ann Neurol. 1979;  5 (4) 331-337
    CrossrefPubMedSearch in Google Scholar
  • 35 Millan M, Hull T L, Hammel J, Remzi F. Portal vein thrombi after restorative proctocolectomy: serious complication without long-term sequelae.  Dis Colon Rectum. 2007;  50 (10) 1540-1544
    CrossrefPubMedSearch in Google Scholar
  • 36 Fichera A, Cicchiello L A, Mendelson D S, Greenstein A J, Heimann T M. Superior mesenteric vein thrombosis after colectomy for inflammatory bowel disease: a not uncommon cause of postoperative acute abdominal pain.  Dis Colon Rectum. 2003;  46 (5) 643-648
    CrossrefPubMedSearch in Google Scholar
  • 37 Remzi F H, Fazio V W, Oncel M et al.. Portal vein thrombi after restorative proctocolectomy.  Surgery. 2002;  132 (4) 655-661 discussion 661-662
    CrossrefPubMedSearch in Google Scholar
  • 38 Köksal A S, Ertugrul I, Dişibeyaz S et al.. Crohn's and Behçet's disease association presenting with superior vena cava thrombosis.  Dig Dis Sci. 2005;  50 (9) 1698-1701
    CrossrefPubMedSearch in Google Scholar
  • 39 Weber T, Huemer G, Tschernich H, Kranz A, Imhof M, Sladen R N. Catheter-induced thrombus in the superior vena cava diagnosed by transesophageal echocardiography.  Acta Anaesthesiol Scand. 1998;  42 (10) 1227-1230
    CrossrefPubMedSearch in Google Scholar
  • 40 Sashi R, Ito I, Watarai J, Miura K, Horie Y. Thrombophlebitis of the inferior vena cava involving the retroperitoneum with Crohn's disease: MR demonstration.  Magn Reson Imaging. 1997;  15 (9) 1099-1101
    CrossrefPubMedSearch in Google Scholar
  • 41 Maccini D M, Berg J C, Bell G A. Budd-Chiari syndrome and Crohn's disease. An unreported association.  Dig Dis Sci. 1989;  34 (12) 1933-1936
    CrossrefPubMedSearch in Google Scholar
  • 42 Socha P, Ryzko J, Janczyk W, Dzik E, Iwanczak B, Krzesiek E. Hepatic vein thrombosis as a complication of ulcerative colitis in a 12-year-old patient.  Dig Dis Sci. 2007;  52 (5) 1293-1298
    CrossrefPubMedSearch in Google Scholar
  • 43 Rahhal R M, Pashankar D S, Bishop W P. Ulcerative colitis complicated by ischemic colitis and Budd Chiari syndrome.  J Pediatr Gastroenterol Nutr. 2005;  40 (1) 94-97
    CrossrefPubMedSearch in Google Scholar
  • 44 Whiteford M H, Moritz M J, Ferber A, Fry R D. Budd-Chiari syndrome complicating restorative proctocolectomy for ulcerative colitis: report of a case.  Dis Colon Rectum. 1999;  42 (9) 1220-1224
    CrossrefPubMedSearch in Google Scholar
  • 45 Di Fabio F, Obrand D, Satin R, Gordon P H. Intra-abdominal venous and arterial thromboembolism in inflammatory bowel disease.  Dis Colon Rectum. 2009;  52 (2) 336-342
    CrossrefPubMedSearch in Google Scholar
  • 46 Condat B, Pessione F, Helene Denninger M, Hillaire S, Valla D. Recent portal or mesenteric venous thrombosis: increased recognition and frequent recanalization on anticoagulant therapy.  Hepatology. 2000;  32 (3) 466-470
    CrossrefPubMedSearch in Google Scholar
  • 47 Sheen C L, Lamparelli H, Milne A, Green I, Ramage J K. Clinical features, diagnosis and outcome of acute portal vein thrombosis.  QJM. 2000;  93 (8) 531-534
    CrossrefPubMedSearch in Google Scholar
  • 48 Martin E C, Laffey K J, Bixon R. Recanalization of the superior mesenteric vein for massive bleeding in Crohn disease.  J Vasc Interv Radiol. 1995;  6 (5) 703-705
    CrossrefPubMedSearch in Google Scholar
  • 49 Palkovits J, Häfner M, Rand T et al.. Portal vein thrombosis in ulcerative colitis complicated by bleeding from gastric varices.  Inflamm Bowel Dis. 2007;  13 (3) 365-366
    CrossrefPubMedSearch in Google Scholar
  • 50 Capron J P, Remond A, Lebrec D, Delamarre J, Dupas J L, Lorriaux A. Gastrointestinal bleeding due to chronic portal vein thrombosis in ulcerative colitis.  Dig Dis Sci. 1979;  24 (3) 232-235
    CrossrefPubMedSearch in Google Scholar
  • 51 Hatoum O A, Spinelli K S, Abu-Hajir M et al.. Mesenteric venous thrombosis in inflammatory bowel disease.  J Clin Gastroenterol. 2005;  39 (1) 27-31
    PubMedSearch in Google Scholar
  • 52 Ball C G, MacLean A R, Buie W D, Smith D F, Raber E L. Portal vein thrombi after ileal pouch-anal anastomosis: its incidence and association with pouchitis.  Surg Today. 2007;  37 (7) 552-557
    CrossrefPubMedSearch in Google Scholar
  • 53 Okada T, Sasaki F, Minagawa N et al.. Postoperative portal and splenic vein thrombosis in children: identification of risk factors.  Pediatr Surg Int. 2005;  21 (11) 918-921
    CrossrefPubMedSearch in Google Scholar
  • 54 Lambley J, Ho Y H. Mesenteric vein thrombosis after proctocolectomy for inflammatory bowel disease.  Dis Colon Rectum. 2003;  46 (12) 1715
    CrossrefPubMedSearch in Google Scholar
  • 55 Farkas L M, Nelson R L, Abcarian H. A case of portal venous system thrombosis in ulcerative colitis.  J Am Coll Surg. 2000;  190 (1) 94
    CrossrefPubMedSearch in Google Scholar
  • 56 Tonelli F, Asteria C R, Fratini G. Acute thrombosis of superior mesenteric vein during restorative proctocolectomy: what to do?.  Int J Colorectal Dis. 2007;  22 (1) 95-97
    PubMedSearch in Google Scholar
  • 57 Lippi G, Franchini M. Pathogenesis of venous thromboembolism: when the cup runneth over.  Semin Thromb Hemost. 2008;  34 (8) 747-761
    Thieme ConnectPubMedSearch in Google Scholar
  • 58 Gormally S M, Bourke W, Kierse B, Monaghan H, McMenamin J, Drumm B. Isolated cerebral thrombo-embolism and Crohn disease.  Eur J Pediatr. 1995;  154 (10) 815-818
    CrossrefPubMedSearch in Google Scholar
  • 59 Jorens P G, Delvigne C R, Hermans C R, Haber I, Holvoet J, De Deyn P P. Cerebral arterial thrombosis preceding ulcerative colitis.  Stroke. 1991;  22 (9) 1212
    CrossrefPubMedSearch in Google Scholar
  • 60 Joshi D, Dickel T, Aga R, Smith-Laing G. Stroke in inflammatory bowel disease: a report of two cases and review of the literature.  Thromb J. 2008;  6 2
    CrossrefPubMedSearch in Google Scholar
  • 61 Freilinger T, Riedel E, Holtmannspötter M, Dichgans M, Peters N. Ischemic stroke and peripheral arterial thromboembolism in a patient with Crohn's disease: a case presentation.  J Neurol Sci. 2008;  266 (1–2) 177-179
    CrossrefPubMedSearch in Google Scholar
  • 62 Standridge S, de los Reyes E. Inflammatory bowel disease and cerebrovascular arterial and venous thromboembolic events in 4 pediatric patients: a case series and review of the literature.  J Child Neurol. 2008;  23 (1) 59-66
    PubMedSearch in Google Scholar
  • 63 Efremidis M, Prappa E, Kardaras F. Acute myocardial infarction in a young patient during an exacerbation of ulcerative colitis.  Int J Cardiol. 1999;  70 (2) 211-212
    CrossrefPubMedSearch in Google Scholar
  • 64 Nogami H, Iiai T, Maruyama S, Tani T, Hatakeyama K. Common carotid arterial thrombosis associated with ulcerative colitis.  World J Gastroenterol. 2007;  13 (11) 1755-1757
    PubMedSearch in Google Scholar
  • 65 Di Fabio F, Obrand D, Satin R, Gordon P H. Successful treatment of extensive splanchnic arterial and portal vein thrombosis associated with ulcerative colitis.  Colorectal Dis. 2009;  11 (6) 653-655
    CrossrefPubMedSearch in Google Scholar
  • 66 Lengle S J, Nadler P, Jordan G W. Arterial thrombosis in ulcerative colitis. Transcatheter thrombolytic therapy.  West J Med. 1995;  162 (6) 543-547
    PubMedSearch in Google Scholar
  • 67 Levy P J, Tabares A H, Olin J W. 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
    PubMedSearch in Google Scholar
  • 68 Tabibian J H, Roth B E. Local thrombolysis: a newer approach to treating inflammatory bowel disease-related thromboembolism.  J Clin Gastroenterol. 2009;  43 (5) 391-398
    CrossrefPubMedSearch in Google Scholar
  • 69 Büller H R, Agnelli G, Hull R D, Hyers T M, Prins M H, Raskob G E. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  Chest. 2004;  126 (3, Suppl) 401S-428S
    CrossrefPubMedSearch in Google Scholar
  • 70 Twig G, Zandman-Goddard G, Szyper-Kravitz M, Shoenfeld Y. Systemic thromboembolism in inflammatory bowel disease: mechanisms and clinical applications.  Ann N Y Acad Sci. 2005;  1051 166-173
    CrossrefPubMedSearch in Google Scholar
  • 71 Wille-Jørgensen P, Rasmussen M S, Andersen B R, Borly L. Heparins and mechanical methods for thromboprophylaxis in colorectal surgery.  Cochrane Database Syst Rev. 2003;  (4) CD001217
    PubMedSearch in Google Scholar
  • 72 Borly L, Wille-Jørgensen P, Rasmussen M S. Systematic review of thromboprophylaxis in colorectal surgery—an update.  Colorectal Dis. 2005;  7 (2) 122-127
    CrossrefPubMedSearch in Google Scholar

Francesco Di FabioM.D. 

Division of Surgery, Southampton General Hospital, GI Business Unit

E level, Tremona Road, Southampton, SO16 6YD, UK

Email: difabiof@hotmail.it

Email: Francesco.DiFabio@SUHT.SWEST.NHS.UK