Inflammatory Bowel Disease Is a Risk Factor for Recurrent Venous Thromboembolism

doi:10.1053/j.gastro.2010.05.026

Gastroenterology

Volume 139, Issue 3, September 2010, Pages 779-787.e1

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https://doi.org/10.1053/j.gastro.2010.05.026 Get rights and content

Background & Aims

Patients with inflammatory bowel disease (IBD) are at increased risk of a first venous thromboembolism (VTE), yet their risk of recurrent VTE is unknown. We performed a cohort study to determine the risk for recurrent VTE among patients with IBD compared with subjects without IBD.

Methods

We assessed 2811 patients with IBD for a history of VTE, recruited from outpatient clinics at 14 referral centers (June 2006–December 2008). Patients with VTE before a diagnosis of IBD or those not confirmed to have VTE, cancer, or a VTE other than deep vein thrombosis or pulmonary embolism, were excluded. Recurrence rates were compared with 1255 prospectively followed patients without IBD that had a first unprovoked VTE (not triggered by trauma, surgery, or pregnancy). The primary end point was symptomatic, objectively confirmed, recurrent VTE after discontinuation of anticoagulation therapy after a first VTE.

Results

Overall, of 116 IBD patients who had a history of first VTE, 86 were unprovoked. The probability of recurrence 5 years after discontinuation of anticoagulation therapy was higher among patients with IBD than patients without IBD (33.4%; 95% confidence interval [CI]: 21.8–45.0 vs 21.7%; 95% CI: 18.8–24.6; P = .01). After adjustment for potential confounders, IBD was an independent risk factor of recurrence (hazard ratio = 2.5; 95% CI: 1.4–4.2; P = .001).

Conclusions

Patients with IBD are at an increased risk of recurrent VTE compared to patients without IBD.

Section snippets

Study Design

The study was performed as a cohort study that included 2 cohorts. One cohort consisted of IBD patients with first VTE. This cohort was used to evaluate the rate and risk factors of recurrent VTE in IBD patients. The second cohort consisted of control patients with first VTE but without IBD. This cohort was used together with the first cohort for the comparison of recurrence rates of VTE between IBD and non-IBD patients. The acquisition of both cohorts will be described in detail here.²⁹

IBD Patients

This

Patient Characteristics

One hundred and forty-two patients with DVT and/or PE after diagnosis of IBD were identified. Twenty-six patients were excluded because of ongoing anticoagulation, leaving 116 patients for further analysis. Table 1 shows the baseline characteristics of these patients. Anticoagulation was discontinued after a median time of 6.0 (interquartile range, 3.2−8.3) months. Median observation time after discontinuation of anticoagulation was 41.8 (interquartile range, 9.7−86.8) months. In 30 (25.9%)

Discussion

Our study shows that IBD patients are at high risk of recurrent thrombosis after a first VTE. Five years after discontinuation of anticoagulant treatment, the probability of recurrence was 29%. This rate was higher than in other studies of IBD patients, in which recurrence rates ranged between 13% and 21%.6, 7, 8 However, results of these former studies had been limited by small patient numbers and methodological shortcomings, including lack of objective diagnosis of first and recurrent VTE and

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Hospitalized patients with inflammatory bowel disease (IBD) are at increased risk of venous thromboembolism (VTE). We aimed to evaluate the effectiveness and safety of prophylactic anticoagulation compared with no anticoagulation in hospitalized patients with IBD. We conducted a retrospective cohort study using a hospital-based database. We included patients with IBD who had a length of hospital stay ≥2 days between 1 January 2016 and 31 December 2019. We excluded patients who had other indications for anticoagulation, users of direct oral anticoagulants, warfarin, therapeutic-intensity heparin, and patients admitted for surgery. We defined exposure to prophylactic anticoagulation using charge codes. The primary effectiveness outcome was VTE. The primary safety outcome was bleeding. We used propensity score matching to reduce potential differences between users and nonusers of anticoagulants and Cox proportional-hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The analysis included 56 194 matched patients with IBD (users of anticoagulants, n = 28 097; nonusers, n = 28 097). In the matched sample, prophylactic use of anticoagulants (vs no use) was associated with a lower rate of VTE (HR, 0.62; 95% CI, 0.41-0.94) and with no difference in the rate of bleeding (HR, 1.05; 95% CI, 0.87-1.26). In this study of hospitalized patients with IBD, prophylactic use of heparin was associated with a lower rate of VTE without increasing bleeding risk compared with no anticoagulation. Our results suggest potential benefits of prophylactic anticoagulation to reduce the burden of VTE in hospitalized patients with IBD.
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Clinical management of patients with deep vein thrombosis (DVT) is centered around their risk of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome (PTS). While chronic inflammatory disease (CID) has been established as a risk factor of (recurrent) VTE, research about its potential impact on PTS is lacking.
We aimed to assess the risk of PTS in patients with CID, stratifying for the use of anti-inflammatory treatment.
Consecutive patients with proximal DVT and no active cancer between 2003 and 2018 received a two-year prospective follow-up. CID included inflammatory bowel disease, rheumatic diseases, and gout. Residual venous obstruction (RVO) was assessed by compressive ultrasound after 3–6 months. PTS was diagnosed using the Villalta score after 6–24 months. Hazard ratios (HR) and odds ratios (OR) were adjusted for patient characteristics. The medical ethics committee approved this study.
In total 82 of 801 patients had CID (10.2 %). PTS more often developed in patients with CID (35.4% vs. 18.9 %, p < 0.001) than in those without CID (HR 1.72 [1.15–2.58]). The prevalence of RVO was similar in patients with and without CID (36.8% vs. 41.4 %), and RVO was strongly associated with PTS in patients with CID (OR 3.21 [1.14–9.03]). Moreover, patients with untreated CID (44 %, n = 36) more often had RVO than those with treated CID (51.6% vs. 26.7 %, p = 0.027), and accordingly had a higher risk of PTS (HR 2.18 [1.04–4.58]).
Patients with CID had an increased risk of developing PTS, especially those without anti-inflammatory treatment, possibly due to an unfavorable impact on RVO-related venous pathology.
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Patients with inflammatory bowel disease (IBD) have an increased risk of developing venous thromboembolic events, which have a considerable impact on morbidity and mortality. Chronic inflammation plays a crucial role in the pathogenesis of thrombotic events in patients with IBD. However, many unresolved questions remain, particularly regarding the mechanisms that determine the persistent inflammatory state independent of disease activity. This review explored the role of gut microbiota dysbiosis and intestinal barrier dysfunction, which are considered distinctive features of IBD, in determining pro-thrombotic tendencies. Gut-derived endotoxemia due to the translocation of bacterial lipopolysaccharides (LPS) from the intestine to the bloodstream and the bacterial metabolite trimethylamine-N-oxide (TMAO) are the most important molecules involved in gut dysbiosis-related thrombosis. The pathogenic prothrombotic pathways linked to LPS and TMAO have been discussed. Finally, we present emerging therapeutic approaches that can help reduce LPS-mediated endotoxemia and TMAO, such as restoring intestinal eubiosis, normalizing intestinal barrier function, and counterbalancing the effects of LPS and TMAO.
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Autoimmune diseases have specific pathophysiologic mechanisms leading to an increased risk of arterial and venous thrombosis. The risk of venous thromboembolism (VTE) varies according to the type and stage of the disease, and to concomitant treatments. In this review, we revise the most common autoimmune disease such as antiphospholipid syndrome, inflammatory myositis, polymyositis and dermatomyositis, rheumatoid arthritis, sarcoidosis, Sjogren syndrome, autoimmune haemolytic anaemia, systemic lupus erythematosus, systemic sclerosis, vasculitis and inflammatory bowel disease. We also provide an overview of pathophysiology responsible for the risk of VTE in each autoimmune disorder, and report current indications to anticoagulant treatment for primary and secondary prevention of VTE.
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: This article has an accompanying continuing medical education activity on page e12. Learning Objective: Upon completion of this exercise, successful learners will be able to identify the risk of recurrent venous thromboembolism in patients with inflammatory bowel disease.

: Conflicts of interest The authors disclose no conflicts.

: Funding The study received funding through the Medical Scientific Fund of the Mayor of the City of Vienna (project number 2551) and the Hochschuljubiläumsstiftung of the City of Vienna (H-806/2005).

View full text

Clinical—Alimentary TractInflammatory Bowel Disease Is a Risk Factor for Recurrent Venous Thromboembolism

Background & Aims

Methods

Results

Conclusions

Section snippets

Study Design

IBD Patients

Patient Characteristics

Discussion

Gastroenterology

Mayo Clin Proc

Lancet

J Thromb Haemost

Lancet

Am J Med

Chest

Lancet

Lancet

Lancet

J Thromb Haemost

J Crohns Colitis

Lancet

Gastroenterology

Am J Gastroenterol

Blood

The course and prognosis of ulcerative colitis. III. Complications

Gut

Inflammatory bowel disease promotes venous thrombosis earlier in life

Scand J Gastroenterol

The incidence of deep venous thrombosis and pulmonary embolism among patients with inflammatory bowel disease: a population-based cohort study

Thromb Haemost

Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism?

Gut

Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden

QJM

Venous thromboembolism in inflammatory bowel disease

Am J Gastroenterol

Overall and cause-specific mortality in ulcerative colitis: meta-analysis of population-based inception cohort studies

Am J Gastroenterol

Rising prevalence of venous thromboembolism and its impact on mortality among hospitalized inflammatory bowel disease patients

Am J Gastroenterol

Inflammation and coagulation in inflammatory bowel disease: the clot thickens

Am J Gastroenterol

Clinical—Alimentary Tract
Inflammatory Bowel Disease Is a Risk Factor for Recurrent Venous Thromboembolism