Inflammatory Bowel Disease: Focus on Venous Thromboembolism

Inflammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn’s disease (CD). Compared with the general population, patients with IBD have a 2- to 3-fold increase in the risk of developing venous thromboembolism (VTE).¹ In one cohort study, the overall relative risk for VTE in IBD patients was 3.47 (95% confidence interval: 2.94-4.09). In this same study, the incidence of deep vein thrombosis was reported as 30.0 per 10,000 person-years for UC and 31.4 per 10,000 person-years for CD patients. The incidence of pulmonary embolism was reported as 19.8 per 10,000 person-years for UC and 10.3 per 10,000 person-years for CD.²

VTE occurs most frequently during phases of active disease and in patients with extended disease (ie, pancolitis in UC, and extensive colonic involvement in CD).³ The mortality rate associated with VTE-related hospitalizations is 2.5 times greater in patients with IBD than in patients who have non—VTE-related hospitalizations.⁴

For patients with IBD, VTE develops primarily in the deep veins of the legs and in the pulmonary system. Less frequently, VTE develops in the cerebrovascular system, portal vein, retinal vein, and mesenteric veins.⁵

In addition to the common risk factors for VTE (eg, advanced age, cancer, prior VTE, venous insufficiency, pregnancy, trauma, frailty and immobility, thrombophilia, major surgery), patients with IBD may have hereditary and acquired risk factors that coexist, thereby multiplying the individual prothrombotic risk. These factors may include active disease, hyperhomocysteinaemia, dehydration, infections, and indwelling catheters.

PROPHYLAXIS AND TREATMENT OF VTE IN IBD

The following measures can be taken to reduce the risk for VTE in IBD patients: ensuring adequate hydration, correcting vitamin deficiencies (especially for B₆, B₁₂, and folate), using compression stockings or pneumatic devices, and early mobilization after surgery. It has been theorized that control of disease activity may also minimize the risk for VTE by reducing the procoagulant factors associated with the inflammation process. Additionally, many of the drugs used in the management of IBD have anti-inflammatory and anticoagulant effects. These medications include mesalamine, azathioprine, b-mercaptopurine, and infliximab.

For patients with a higher risk for VTE (ie, patients with active disease or who are hospitalized), pharmacologic thromboprophylaxis with low-molecular-weight heparin (LMWH) and unfractionated heparin is recommended in various practice guidelines.^6,7

It is important to point out that even though VTE is a significant cause of morbidity and mortality in IBD patients, the number of hospitalized patients who receive adequate prophylaxis remains low. Inadequate prophylaxis is mainly a result of gastroenterologists’ lack of awareness of both the increased risk for VTE in IBD patients and the guideline-recommended use of pharmacologic prophylaxis in hospitalized patients, as well as concern about the safety of anticoagulant use in IBD patients with active disease.^8,9 Another controversial issue is whether to extend thromboprophylaxis to all ambulatory patients with disease flare-ups or to limit it to patients deemed to be at higher risk for VTE.

As clinicians, we should aim to provide individual assessments for the risk of VTE in patients with IBD. This includes considering personal and family histories of VTE, the presence of cardiovascular or respiratory disease, the presence of obesity, use of oral contraceptives, smoking status, genetic prothrombotic risk factors, reduced mobility, and the presence of venous catheters. ¹⁰

Treatment of VTE in IBD patients is the same as in patients without IBD. If there is no active bleeding and no contraindication to anticoagulation, the preferred treatment is LMWH, which is usually transitioned to an oral anticoagulant (ie, warfarin). The duration of treatment has not been well established, given the possibility of VTE recurrence. However, as for most patients, the length of treatment should be balanced with the bleeding risk associated with anticoagulation.

Dr. Resseguie is an advanced practice anticoagulation pharmacist for the Brigham & Women’s Hospital Anticoagulation Management Service in Boston, Massachusetts

References:

• 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;37:953-962.
• Bernstein CN, Blanchard JF, Houston DS, Wajda A. The incidence of deep vein thrombosis and pulmonary embolism among patients with inflammatory bowel disease: a population-based cohort study. Thromb Haemost. 2001;85:430-434.
• Miehsler W, Reinisch W, Valie E, et al. Is inflammatory bowel disease and independent and disease specific risk factor for venous thromboembolism? Gut. 2004:53:542-548.
• Nguyen GC, Sam J. Rising prevalence of venous thromboembolism and its impact on mortality among hospitalized inflammatory bowel disease patients. Am J Gastroenterol. 2008;103:2272-2280.
• Papay A, Miehsler W, Tilg H, et al. Clinical presentation of venous thromboembolism in inflammatory bowel disease. J Crohns Colitis. 2013;7:723-729.
• Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e195S-e226S.
• Mowat C, Cole A, Windsor A, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2011;60:571-607.
• Sam JJ, Bernstein CN, Razik R, Thanabalan R, Nguyen GC. Physicians’ perceptions of risks and practices in venous thromboembolism prophylaxis in inflammatory bowel disease. Dig Dis Sci. 2013;58:46-52.
• 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:e1-e6.
• Zitomersky NL, Verhave M, Trenor CC. Thrombosis and inflammatory bowel disease: a call for improved awareness and prevention. Inflamm Bowel Dis. 2011;17:458-470.