Warfarin Institute of America
DEDICATED TO YOUR HEALTH SINCE 2000
IS CROHN'S DISEASE ASSOCIATED WITH A HIGH RISK OF BLOOD CLOTS?
by
Jerilyn Cook, Pharm D. Candidate
University of Colorado School of Pharmacy
Crohn’s disease is a disease of the intestinal tract that results in chronic inflammation. Inflammatory bowel disease (IBD) is often used to describe Crohn’s disease as will as ulcerative colitis. They both cause watery and/or bloody diarrhea and painful abdominal cramping. Crohn’s and ulcerative colitis differ in where they occur and the extent of their penetration into intestinal tissue. Crohn’s disease can occur anywhere in the digestive tract and the inflammation can penetrate into all layers of the affected area, whereas ulcerative colitis usually only affects the innermost lining of the large intestine and rectum.1
Signs and symptoms of Crohn’s disease include diarrhea, abdominal pain/cramping, bloody stool, and weight loss or anorexia. The cause of Crohn’s is unknown, but environmental factors, hereditary factors, and factors relating to the body’s immune response are thought to be involved. Crohn’s is seen equally in men and women, but more frequently diagnosed in people at a young age, in Caucasians, and in those living in urban areas. Complications of Crohn’s include ulcers, fistulas, obstruction in the gastrointestinal tract, malnutrition, and thromboembolism.1
Patients with inflammatory bowel disease (IBD), which includes Crohn’s disease, have been found to be at increased risk of venous thromboembolism (VTE) compared to controls matched by age, sex and geographic area.2 This risk is estimated to be 3 times higher in those patients with IBD compared to the general population.2-4 Deep vein thrombosis and pulmonary embolism are the most common presentations for VTE, but may occur in other areas It has also been observed that those patients with more severe colonic disease and/or active disease appear to be at higher risk for thromboembolic disease3. Furthermore, IBD patients are exposed more frequently to risk factors associated with developing VTE such as frequent hospitalizations, immobilization, malignancies, and surgeries.3 However, clinical trials have controlled for or performed statistical analyses to rule out these factors and still observed increased blood clots in IBD patients. The increased risk for VTE does not appear to be related solely to the inflammatory state associated with IBD. The same increases were not observed in rheumatoid arthritis and celiac disease, which also have inflammatory components.2,4 The increase in VTE seen in IBD patients carries with it a high incidence of morbidity and mortality leading to the search for possible etiologies including possible thrombophilic abnormalities leading to a hypercoaguable state or factors associated with the disease itself. 2,3
Possible thrombophilic abnormalities linked to IBD and Crohn’s disease include Factor V Leiden, elevated homocysteine levels, and alterations in clotting and coagulation factors. Factor V Leiden (FVL) is a genetic disease characterized by an altered anticoagulant response. This results in elevated thrombin and increased incidence of blood clots.2 It is known to be the most common cause of VTE in the general population seen in about 20-30% of people with blood clots. 3,5 Most studies have found that the incidence of FVL in Crohn’s patients is similar to that seen in the general population, suggesting that this is not the answer. Homocysteine is an amino acid used to make protein in the body. Elevated homocysteine levels are thought to be associated with stroke, heart attacks and thromboembolisms. These elevated levels have also been observed in IBD, suggesting a relation between homocysteine, IBD and thromboembolic events. Homocysteine levels can be decreased with the addition of folate and vitamin B12, which have not led to a decrease in the incidence of blood clots observed in IBD patients. In addition, high homocysteine levels have been observed in patients with celiac disease where there is no observed elevated risk for developing blood clots. 2,4 Clotting factors and platelet activation have been found to be elevated and to correlate with disease activity in IBD. This includes abnormal platelet function, platelet factors, and an alteration in the fibrinolytic system, but the specific role of these factors in IBD has not been established.4,5 Therefore, the relationships between the above listed factors and the hypercoaguable state encountered in IBD are inconclusive and have not been proven in clinical studies. This has forced researchers to consider other possibilities. 2-5
Miehsler et al found that 60% of IBD patients had a VTE during active bouts of their disease or during disease complications including abscess and fistulas. This led to the hypothesis that endotoxins may contribute to the hypercoaguable state seen in IBD. Elevated endotoxins are observed in active disease as well as complications associated with IBD. These endotoxins activate the coagulation cascade when they interact with other inflammatory chemicals in the body, which are also present in active IBD. Microclots were observed when endotoxins were introduced into patients with IBD, but the same clot formation was not seen in non-IBD subjects.4 In addition, alteration in the coagulation cascade have already been noted in patients with active IBD independent of endotoxin levels so the two combined could explain the increase in VTE.2,4 This is just one possible explanation and research still needs to be done looking at the relationship between thromboembolic events and inflammatory bowel diseases including Crohn’s disease. Unfortunately without a reason for this observed increase, it is suggested that all IBD patients with thromboembolic events should have a comprehensive thrombophilia assessment. In addition, appropriate therapy should be started when warranted due to the morbidity and mortality associated with venous thromboembolic complications.3
References:
1. Crohn’s Disease. Mayo Clinic website. Available at http://www.mayoclinic.com/health/crohns-disease/DS00104/DSECTION=7. Accessed August 24, 2006.
2. SriRajaskanthan R, Winter M, and Muller A. Venous thrombosis in inflammatory bowel disease. European Journal of Gastroenterology and Hepatology 2005;17:697-700.
3 Solem C, Loftus E, Tremaine W, and Sandborn W. Venous thromboembolism in inflammatory bowel disease. American Journal of Gastroenterology 2004;99(1):97-101.
4. Miehsler W, Reinisch W, Valic E, Osterode W, Tillinger W, Feichtenschlager T, et al. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? Gut 2004;53:542-548.
5. Bernstein CN, Blanchard JF, Houston DS, and Wajda A. The incidence of deep venous thrombosis and pulmonary embolism among patients with inflammatory bowel disease: A population-based cohort study 2001;85:430-434.
© 2006 Jerilyn Cook Used By Permission
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Last updated June 13, 2007
