Ulcerative Colitis Is Associated With an Increased Risk of Venous Thromboembolism in the Postoperative Period

Abstract Background Colectomy for ulcerative colitis (UC) has been associated with postoperative morbidity and mortality, including venous thromboembolism (VTE). Patients with inflammatory bowel diseases (IBD) have a 2 to 4-fold increased risk for developing VTE, as compared to non-IBD patients. Due to recent concerns on increased VTE associated with tofacitinib exposure, we aimed to evaluate the 180-day postoperative VTE risk in UC patients undergoing colectomy after tofacitinib use in comparison to patients failing biologicals and undergoing the same surgery. Methods This retrospective cohort study included all UC patients who underwent colectomy between 2014 and 2020 in our tertiary IBD center. All medical charts were reviewed, and clinically relevant information extracted, including indication for colectomy, development of postoperative VTE (deep venous thrombosis, pulmonary or extra-pulmonary embolisms) within 180 days of surgery, low-molecular weight heparin (LMWH) prophylaxis and perioperative therapy exposure (steroids within 1 month prior to surgery, biologicals or tofacitinib within 3 months prior to surgery). Results One-hundred seven UC patients (49.5% women, median [IQR] age 38.0 [27.0 – 53.0] years) underwent colectomy due to refractory disease (n=93), dysplasia or carcinoma (n=12) or polyposis (n=2) (Table 1). Thirty-six (33.6%) patients were operated urgently. At the time of surgery, 44 (41.1%) were on steroids, 38 (35.5%) on anti-TNF agents, 27 (25.2%) on vedolizumab/etrolizumab, 6 (5.6%) on anti-IL12/23 agents and 12 (11.2%) on tofacitinib. All patients received antithrombotic prophylactic LMWH postoperatively. During the 180-day postoperative period, 3 (2.8%) patients developed an intra-abdominal thrombosis, none of them had a history of VTE. Two thromboses were found by coincidence on CT scans which were performed in light of postoperative fever and inflammatory blood tests, the other patient was symptomatic. All 3 patients had been exposed to vedolizumab: one had an underlying malignancy (colon adenocarcinoma), the 2 others also had been exposed to corticosteroids prior to colectomy. No VTE was seen in the patients who underwent colectomy while on tofacitinib. Conclusion The overall risk for UC patients to develop VTE after colectomy is low with adequate antithrombotic prophylactic therapy. In particular, we did not observe any VTE in our colectomy patients who were exposed to tofacitinib prior to surgery. The three patients who developed VTE despite LMWH had additional risk factors (concomitant steroid use, active cancer).

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Risk of venous thromboembolism in immune-mediated inflammatory diseases: a UK matched cohort study

RMD Open ◽

10.1136/rmdopen-2020-001392 ◽

2020 ◽

Vol 6 (3) ◽

pp. e001392

Author(s):

James Galloway ◽

Kevin Barrett ◽

Peter Irving ◽

Kaivan Khavandi ◽

Monica Nijher ◽

...

Keyword(s):

Risk Factors ◽

Ulcerative Colitis ◽

Venous Thromboembolism ◽

Proportional Hazards ◽

Inflammatory Diseases ◽

Clinical Information ◽

Cox Proportional Hazards ◽

Smoking History ◽

Immune Mediated ◽

Increased Risk

ObjectivesTo describe the risk of venous thromboembolism (VTE), and risk factors for VTE, in people with immune-mediated inflammatory diseases (IMID) (ulcerative colitis, Crohn’s disease (CD), rheumatoid arthritis (RA) and psoriatic arthritis (PsA)), compared with a matched control population.MethodsA total of 53 378 people with an IMID were identified over 1999–2019 in the UK Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database and were matched to 213 512 people without an IMID. The association between the presence of any IMID, and each IMID separately, and risk of VTE was estimated using unadjusted and multivariable-adjusted Cox proportional hazards models. The prevalence of VTE risk factors, and associations between VTE risk factors and risk of VTE, were estimated in people with and without an IMID.ResultsPeople with an IMID were at increased risk of VTE (adjusted HR [aHR] 1.46, 95% CI 1.36,1.56), compared with matched controls. When assessing individual diseases, risk was increased for CD (aHR 1.74, 95% CI 1.45 to 2.08), ulcerative colitis (aHR 1.27, 95% CI 1.10 to 1.45) and RA (aHR 1.54, 95% CI 1.40 to 1.70) but there was no evidence of an association for PsA (aHR 1.21, 95% CI 0.96 to 1.52). In people with an IMID, independent risk factors for VTE included male sex, overweight/obese body mass index, current smoking, history of fracture, and, across study follow-up, abnormal platelet count.ConclusionsVTE risk is increased in people with IMIDs. Routinely available clinical information may be helpful to identify individuals with an IMID at increased future risk of VTE.Observational study registration numberClinicaltrials.gov (NCT03835780).

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Improving the Quality of Inpatient Ulcerative Colitis Management: Promoting Evidence-Based Practice and Reducing Care Variation With an Inpatient Protocol

Inflammatory Bowel Diseases ◽

10.1093/ibd/izz066 ◽

2019 ◽

Vol 25 (11) ◽

pp. 1822-1827 ◽

Cited By ~ 5

Author(s):

Sara M Lewin ◽

Ryan A McConnell ◽

Roshan Patel ◽

Suzanne R Sharpton ◽

Fernando Velayos ◽

...

Keyword(s):

Ulcerative Colitis ◽

Venous Thromboembolism ◽

Oral Morphine ◽

Quality Improvement Intervention ◽

Evidence Based ◽

Thromboembolism Prophylaxis ◽

Disease Extent ◽

Vte Prophylaxis ◽

Increased Risk ◽

Evidence Based Care

Abstarct Background Hospitalization for ulcerative colitis is a high-risk period associated with increased risk of Clostridium difficile infection, thromboembolism, and opiate use. The study aim was to develop and implement a quality-improvement intervention for inpatient ulcerative colitis management that standardizes gastroenterology consultant recommendations and improves delivery of evidence-based care. Methods All adult patients hospitalized for ulcerative colitis between July 1, 2014, and December 31, 2017, who received intravenous corticosteroids were included. On July 1, 2016, the UCSF Inpatient Ulcerative Colitis Protocol was implemented, featuring standardized core recommendations and a daily checklist for gastroenterology consultant notes, a bundled IBD electronic order set, and an opiate awareness campaign. The composite primary outcome was adherence to all 3 evidence-based care metrics: C. difficile testing performed, pharmacologic venous thromboembolism (VTE) prophylaxis ordered, and opiates avoided. Results Ninety-three ulcerative colitis hospitalizations occurred, including 36 preintervention and 57 postintervention. Age, gender, disease duration, disease extent, and medication use were similar preintervention and postintervention. C. difficile testing was performed in 100% of hospitalizations. Venous thromboembolism prophylaxis was ordered on 84% of hospital days before intervention compared with 100% after intervention (P ≤ 0.001). Opiates were administered in 67% of preintervention hospitalizations, compared with 53% of postintervention hospitalizations (P = 0.18). The median daily dose of oral morphine equivalents decreased from 12.1 mg before intervention to 0.5 mg after intervention (P = 0.02). The composite outcome of adherence to all 3 metrics was higher after intervention (25% vs. 47%, P = 0.03). Conclusions Evidence-based inpatient ulcerative colitis management may be optimized with standardized algorithms that reinforce core principles, reduce care variation, and do not require IBD specialists to implement.

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Risk of venous thromboembolism following surgical treatment of superficial venous incompetence

VASA ◽

10.1024/0301-1526/a000656 ◽

2017 ◽

Vol 46 (6) ◽

pp. 484-489 ◽

Cited By ~ 7

Author(s):

Tom Barker ◽

Felicity Evison ◽

Ruth Benson ◽

Alok Tiwari

Keyword(s):

Venous Thromboembolism ◽

Varicose Vein ◽

Lower Incidence ◽

Varicose Veins ◽

Secondary Data ◽

Foam Sclerotherapy ◽

Increased Risk ◽

Significant Difference ◽

Chi Squared ◽

One Year

Abstract. Background: The invasive management of varicose veins has a known risk of post-operative deep venous thrombosis and subsequent pulmonary embolism. The aim of this study was to evaluate absolute and relative risk of venous thromboembolism (VTE) following commonly used varicose vein procedures. Patients and methods: A retrospective analysis of secondary data using Hospital Episode Statistics database was performed for all varicose vein procedures performed between 2003 and 2013 and all readmissions for VTE in the same patients within 30 days, 90 days, and one year. Comparison of the incidence of VTEs between procedures was performed using a Pearson’s Chi-squared test. Results: In total, 261,169 varicose vein procedures were performed during the period studied. There were 686 VTEs recorded at 30 days (0.26 % incidence), 884 at 90 days (0.34 % incidence), and 1,246 at one year (0.48 % incidence). The VTE incidence for different procedures was between 0.15–0.35 % at 30 days, 0.26–0.50 % at 90 days, and 0.46–0.58 % at one year. At 30 days there was a significantly lower incidence of VTEs for foam sclerotherapy compared to other procedures (p = 0.01). There was no difference in VTE incidence between procedures at 90 days (p = 0.13) or one year (p = 0.16). Conclusions: Patients undergoing varicose vein procedures have a small but appreciable increased risk of VTE compared to the general population, with the effect persisting at one year. Foam sclerotherapy had a lower incidence of VTE compared to other procedures at 30 days, but this effect did not persist at 90 days or at one year. There was no other significant difference in the incidence of VTE between open, endovenous, and foam sclerotherapy treatments.

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High incidence of postoperative silent venous thromboembolism in ulcerative colitis: a retrospective observational study

BMC Surgery ◽

10.1186/s12893-021-01250-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Norimitsu Shimada ◽

Hiroki Ohge ◽

Hiroki Kitagawa ◽

Kosuke Yoshimura ◽

Norifumi Shigemoto ◽

...

Keyword(s):

Ulcerative Colitis ◽

Venous Thromboembolism ◽

Total Colectomy ◽

Univariate Analysis ◽

Operation Time ◽

High Serum ◽

Total Proctocolectomy ◽

Colon And Rectum ◽

Predictive Risk ◽

D Dimer

Abstract Background The incidence of postoperative venous thromboembolism (VTE) is high in patients with inflammatory bowel disease. We aimed to analyze the incidence and predictive factors of postoperative VTE in patients with ulcerative colitis. Methods Patients with ulcerative colitis who underwent colon and rectum surgery during 2010–2018 were included. We retrospectively investigated the incidence of postoperative VTE. Results A total of 140 colorectal surgery cases were included. Postoperative VTE was detected in 24 (17.1 %). Portal–mesenteric venous thrombosis was the most frequent VTE (18 cases; 75 %); of these, 15 patients underwent total proctocolectomy (TPC) with ileal pouch–anal anastomosis (IPAA). In univariate analysis, VTE occurred more frequently in patients with neoplasia than in those refractory to medications (27.2 % vs. 12.5 %; p < 0.031). TPC with IPAA was more often associated with VTE development (28 %) than total colectomy (10.5 %) or proctectomy (5.9 %). On logistic regression analysis, TPC with IPAA, total colectomy, long operation time (> 4 h), and high serum D-dimer level (> 5.3 µg/mL) on the day following surgery were identified as predictive risk factors. Conclusions Postoperative VTE occurred frequently and asymptomatically, especially after TPC with IPAA. Serum D-dimer level on the day after surgery may be a useful predictor of VTE.

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Exploring the Relationship between Biologics and Postoperative Surgical Morbidity in Ulcerative Colitis: A Review

Journal of Clinical Medicine ◽

10.3390/jcm10040710 ◽

2021 ◽

Vol 10 (4) ◽

pp. 710

Author(s):

Abel Botelho Quaresma ◽

Fernanda da Silva Barbosa Baraúna ◽

Fábio Vieira Teixeira ◽

Rogério Saad-Hossne ◽

Paulo Gustavo Kotze

Keyword(s):

Ulcerative Colitis ◽

Postoperative Complications ◽

Meta Analysis ◽

Qualitative Evaluation ◽

Complication Rates ◽

Surgical Morbidity ◽

Randomized Studies ◽

Pubmed Database ◽

Increased Risk ◽

The Impact

Background: With the paradigm shift related to the overspread use of biological agents in the treatment of inflammatory bowel diseases (IBD), several questions emerged from the surgical perspective. Whether the use of biologicals would be associated with higher rates of postoperative complications in ulcerative colitis (UC) patients still remains controversial. Aims: We aimed to analyze the literature, searching for studies that correlated postoperative complications and preoperative exposure to biologics in UC patients, and synthesize these data qualitatively in order to check the possible impact of biologics on postoperative surgical morbidity in this population. Methods: Included studies were identified by electronic search in the PUBMED database according to the PRISMA (Preferred Items of Reports for Systematic Reviews and Meta-Analysis) guidelines. The quality and bias assessments were performed by MINORS (methodological index for non-randomized studies) criteria for non-randomized studies. Results: 608 studies were initially identified, 22 of which were selected for qualitative evaluation. From those, 19 studies (17 retrospective and two prospective) included preoperative anti-TNF. Seven described an increased risk of postoperative complications, and 12 showed no significant increase postoperative morbidity. Only three studies included surgical UC patients with previous use of vedolizumab, two retrospective and one prospective, all with no significant correlation between the drug and an increase in postoperative complication rates. Conclusions: Despite conflicting results, most studies have not shown increased complication rates after abdominal surgical procedures in patients with UC with preoperative exposure to biologics. Further prospective studies are needed to better establish the impact of preoperative biologics and surgical complications in UC.

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Causal effect of renal function on venous thromboembolism: a two-sample Mendelian randomization investigation

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-021-02494-4 ◽

2021 ◽

Author(s):

Shuai Yuan ◽

Maria Bruzelius ◽

Susanna C. Larsson

Keyword(s):

Renal Function ◽

Venous Thromboembolism ◽

Mendelian Randomization ◽

Causal Effect ◽

Meta Analysis ◽

Genome Wide Association Studies ◽

Uk Biobank ◽

Genome Wide ◽

Increased Risk ◽

Mr Study

AbstractWhether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10−8) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.

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OP0034 DOES THE RISK OF VENOUS THROMBOEMBOLISM VARY WITH DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.353 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 23.2-24

Author(s):

V. Molander ◽

H. Bower ◽

J. Askling

Keyword(s):

Rheumatoid Arthritis ◽

Logistic Regression ◽

Venous Thromboembolism ◽

Disease Activity ◽

Das28 Score ◽

Logistic Regression Models ◽

Highly Active ◽

Increased Risk ◽

Das28 Remission ◽

One Year

Background:Patients with rheumatoid arthritis (RA) are at increased risk for venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) (1). Several established risk factors of VTE, such as age, immobilization and comorbid conditions, occur more often patients with RA (2). In addition, inflammation may in itself also increase VTE risk by upregulating procoagolatory factors and causing endothelial damage (3). Recent reports indicate an increased risk of VTE in RA patients treated with JAK-inhibitors (4), pointing to the need to better understand how inflammation measured as clinical RA disease activity influences VTE risk.Objectives:To investigate the relationship between clinical RA disease activity and incidence of VTE.Methods:Patients with RA were identified from the Swedish Rheumatology Quality Register (SRQ) between July 1st2006 and December 31st2017. Clinical rheumatology data for these patients were obtained from the visits recorded in SRQ, and linked to national registers capturing data on VTE events and comorbid conditions. For each such rheumatologist visit, we defined a one-year period after the visit and determined whether a VTE event had occurred within this period or not. A visit followed by a VTE event was categorized as a case, all other visits were used as controls. Each patient could contribute to several visits. The DAS28 score registered at the visit was stratified into remission (0-2.5) vs. low (2.6-3.1), moderate (3.2-5.1) and high (>5.1) disease activity. Logistic regression with robust cluster standard errors was used to estimate the association between the DAS28 score and VTE.Results:We identified 46,311 patients with RA who contributed data from 320,094 visits. Among these, 2,257 visits (0.7% of all visits) in 1345 unique individuals were followed by a VTE within the one-year window. Of these, 1391 were DVT events and 866 were PE events. Figure 1 displays the absolute probabilities of a VTE in this one-year window, and odds ratios for VTE by each DAS28 category, using DAS28 remission as reference. The one-year risk of a VTE increased from 0.5% in patients in DAS28 remission, to 1.1% in patients with DAS28 high disease activity (DAS28 above 5.1). The age- and sex-adjusted odds ratio for a VTE event in highly active RA compared to RA in remission was 2.12 (95% CI 1.80-2.47). A different analysis, in which each patient could only contribute to one visit, yielded similar results.Figure 1.Odds ratios (OR) comparing the odds of VTE for DAS28 activity categories versus remission. Grey estimates are from unadjusted logistic regression models, black estimates are from logistic regression models adjusted for age and sex. Absolute one-year risk of VTE are estimated from unadjusted models.Conclusion:This study demonstrates a strong association between clinical RA inflammatory activity as measured through DAS28 and risk of VTE. Among patients with high disease activity one in a hundred will develop a VTE within the coming year. These findings highlight the need for proper VTE risk assessment in patients with active RA, and confirm that patients with highly active RA, such as those recruited to trials for treatment with new drugs, are already at particularly elevated risk of VTE.References:[1]Holmqvist et al. Risk of venous thromboembolism in patients with rheumatoid arthritis and association with disease duration and hospitalization. JAMA. 2012;308(13):1350-6.[2]Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol. 2007;44(2):62-9.[3]Xu J et al. Inflammation, innate immunity and blood coagulation. Hamostaseologie. 2010;30(1):5-6, 8-9.[4]FDA. Safety trial finds risk of blood clots in the lungs and death with higher dose of tofacitinib (Xeljanz, Xeljanz XR) in rheumatoid arthritis patients; FDA to investigate. 2019.Acknowledgments:Many thanks to all patients and rheumatologists persistently filling out the SRQ.Disclosure of Interests:Viktor Molander: None declared, Hannah Bower: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma

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Inflammatory Bowel Disease and Risk of Major Bleeding During Anticoagulation for Venous Thromboembolism

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa337 ◽

2021 ◽

Author(s):

Susanna Scharrer ◽

Christian Primas ◽

Sabine Eichinger ◽

Sebastian Tonko ◽

Maximilian Kutschera ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Venous Thromboembolism ◽

Incidence Rate ◽

Rate Ratio ◽

Incidence Rate Ratio ◽

Fatal Bleeding ◽

Adjusted Incidence Rate ◽

Inflammatory Bowel ◽

Adjusted Incidence

Abstract Background Little is known about the bleeding risk in patients with inflammatory bowel disease (IBD) and venous thromboembolism (VTE) treated with anticoagulation. Our aim was to elucidate the rate of major bleeding (MB) events in a well-defined cohort of patients with IBD during anticoagulation after VTE. Methods This study is a retrospective follow-up analysis of a multicenter cohort study investigating the incidence and recurrence rate of VTE in IBD. Data on MB and IBD- and VTE-related parameters were collected via telephone interview and chart review. The objective of the study was to evaluate the impact of anticoagulation for VTE on the risk of MB by comparing time periods with anticoagulation vs those without anticoagulation. A random-effects Poisson regression model was used. Results We included 107 patients (52 women, 40 with ulcerative colitis, 64 with Crohn disease, and 3 with unclassified IBD) in the study. The overall observation time was 388 patient-years with and 1445 patient-years without anticoagulation. In total, 23 MB events were registered in 21 patients, among whom 13 MB events occurred without anticoagulation and 10 occurred with anticoagulation. No fatal bleeding during anticoagulation was registered. The incidence rate for MB events was 2.6/100 patient-years during periods exposed to anticoagulation and 0.9/100 patient-years during the unexposed time. Exposure to anticoagulation (adjusted incidence rate ratio, 3.7; 95% confidence interval, 1.5-9.0; P = 0.003) and ulcerative colitis (adjusted incidence rate ratio, 3.5; 95% confidence interval, 1.5-8.1; P = 0.003) were independent risk factors for MB events. Conclusion The risk of major but not fatal bleeding is increased in patients with IBD during anticoagulation. Our findings indicate that this risk may be outweighed by the high VTE recurrence rate in patients with IBD.

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