Risk of Venous Thromboembolism in Patients with Inflammatory Bowel Disease Extends beyond Hospitalization

Venous thromboembolism (VTE) is estimated to affect as many as 900,000 Americans each year, causing between 60,000 and 100,000 deaths.1 Pulmonary embolism (PE) is particularly fatal, with one-quarter of patients presenting with sudden death.1 Hospitalized patients are at elevated risk for VTE over the general population, with patients with active cancer, reduced mobility, prior h/o VTE, and known thrombophilic condition at greatest risk.2 As such, the American College of Chest Physicians (ACCP) recommends anticoagulant thromboprophylaxis for acutely ill hospitalized medical patients at increased risk of thrombosis and not bleeding or at high risk for bleeding.2 Patients with recent surgery are also at higher VTE risk, especially those undergoing abdominopelvic surgery, those with cancer, and those who develop surgical complications.3 The ACCP recommends pharmacologic thromboprophylaxis for abdominopelvic surgery patients at moderate or high risk for VTE, unless the risk of major bleeding complication is high.3 Patients with inflammatory bowel disease (IBD) are at a 3-fold higher risk of VTE over non-IBD patients, especially when hospitalized and during flares.4–6 Unfortunately, they are also at increased risk for gastrointestinal bleeding, complicating their VTE treatment and prophylaxis. Anticoagulation thromboprophylaxis is generally recommended for IBD patients hospitalized with moderate to severe flares without severe bleeding and those hospitalized for indications unrelated to IBD.7 Anticoagulation prophylaxis is also recommended by some for patients with prior VTE being treated on an outpatient basis for moderate to severe flares.7 However, VTE risk persists beyond hospital discharge. In a review of 1897 patients with a confirmed episode of VTE, 74% occurred in the outpatient setting.8 A significant proportion of patients had undergone surgery (23%) or were hospitalized (37%) in the 3 months preceding VTE. Benlice et al reported a 30-day VTE rate of 2.5% in 24,182 IBD patients undergoing elective abdominopelvic surgery, with 41% (252 of 614) of events occurring after hospital discharge.9 Nonetheless, extended-duration thromboprophylaxis for hospitalized nonsurgical patients is generally advised against due to risk-benefit and cost considerations.2 For example, in a trial of 6085 hospitalized patients with acute medical illness in which participants were randomized to 38 ± 4 days of enoxaparin prophylaxis vs placebo, treatment reduced VTE incidence (−1.53% absolute risk; 95% CI, −2.54% to −0.52%) but increased major bleeding complications (0.5%; 95% CI, 0.12% to 0.89%).10 The use of prolonged thromboprophylaxis (at least 14 days) following abdominopelvic surgery has been more widely studied, with a recent Cochrane review showing an overall incidence of VTE of 5.2% vs 13.2% in patients who received out-of-hospital low molecular weight heparin compared with those who did not (odds ratio [OR] 0.38, 95% CI, 0.26 to 0.54).11 Accordingly, multiple clinical societies recommend extended-duration pharmacologic prophylaxis with low molecular weight heparin for certain high-VTE-risk patients undergoing abdominal or pelvic surgery, such as those with cancer.3, 12 These same thought leaders, however, have not specifically addressed extended-duration VTE prophylaxis in patients with IBD. In this study, McCurdy et al compared incidence of postdischarge VTE in nonsurgical and surgical IBD patients to that in non-IBD controls using propensity score matching for VTE risk factors. Patients and hospitalizations were identified using Ontario health administrative data sets, which provide information for >99% of residents. In all, 81,900 IBD discharges were compared with 371,964 non-IBD discharges. The nonsurgical cohorts were ideally matched, whereas in the surgical cohort, non-IBD controls were older, had slightly more comorbidities, and were more likely to have an urgent admission. The cumulative VTE incidence was 2.3% in nonsurgical IBD patients and 1.6% in surgical IBD patients. The median time to VTE was 74 days for nonsurgical IBD patients and 26 days for surgical IBD patients. Nonsurgical IBD patients had a 1.7-fold greater risk of VTE compared with controls at 1 month and throughout 12 months, with ulcerative colitis (UC) patients having higher risk than Crohn’s disease (CD) patients up to 6 months posthospitalization. After adjusting for risk factors, surgical IBD patients were also more likely to develop postdischarge VTE than non-IBD surgical controls at 1 month and at 12 months due to risk in UC (hazard ratio [HR] 1.68 and HR 1.78, respectively), but not CD patients. However, these differences disappeared when only urgent hospital admissions were included, presumably due to higher total VTE rates in all patients. Finally, postdischarge VTE incidence was found to increase over the 2002 to 2016 study period in both nonsurgical IBD and non-IBD control patients, but not surgical patients. This study was strengthened by its large size and inclusivity as a population-based investigation. In addition, by propensity matching, the authors created a study environment closer to actual randomization. Results are concordant with prior published works, including one study by Ali et al that showed a higher 30-day VTE rate in IBD patients undergoing colon resection compared with patients undergoing colectomy for diverticulitis (3.1% vs 2.4%, P < 0.001) and a higher 30-day VTE rate in UC than CD patients (4.1% vs 2.1%, P < 0.001). On the other hand, patients who did not require hospital-level care for VTE events were not captured in this study, potentially confounding the results and likely resulting in underestimation of overall VTE incidence. Disease severity, a factor known to be associated with VTE risk, was also not accounted for in propensity matching. In addition, because IBD patients typically have closer health care contact and more frequent postoperative imaging studies, VTE detection is likely higher in this patient population, potentially overestimating the increased rate over non-IBD patients. Nevertheless, this study clearly demonstrates that nonsurgical IBD patients and postoperative UC patients have a significantly elevated VTE risk that extends from hospitalization to 12 months afterwards. Venous thromboembolism rates in hospitalized and postoperative IBD patients approach those in patients with abdominal malignancies,13–15 in whom extended duration thromboprophylaxis following surgical hospitalizations is currently advised. In one prospective study of over 16,000 patients undergoing colorectal surgery, 90-day VTE rates were actually lower in cancer patients compared with those with IBD (2.1% vs 2.6%, P < 0.001).16 Therefore, when added to previous literature, this report compels the need to consider extended-duration anticoagulant thromboprophylaxis in hospitalized and perioperative IBD patients, especially those with additional VTE risk factors. At a minimum, patients should be educated regarding signs and symptoms of VTE and provided resources for obtaining timely care should these occur. Cost and adverse events, in particular gastrointestinal and other bleeding, need to be further examined. In the future, randomized controlled trials would help guide the use of chemoprophylaxis in this patient population.

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