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A postdischarge venous thromboembolism risk calculator for inflammatory bowel disease surgery

Published:October 16, 2020DOI:https://doi.org/10.1016/j.surg.2020.09.006

      Abstract

      Background

      Guidelines recommend extended chemoprophylaxis for venous thromboembolism in high-risk patients having operations for inflammatory bowel disease. Quantifying patients' risk of venous thromboembolism, however, remains challenging. We sought (1) to identify factors associated with postdischarge venous thromboembolism in patients undergoing colorectal resection for inflammatory bowel disease and (2) to develop a postdischarge venous thromboembolism risk calculator to guide prescribing of extended chemoprophylaxis.

      Methods

      Patients who underwent an operation for inflammatory bowel disease from 2012 to 2018 were identified from the American College of Surgeons National Surgical Quality Improvement Program for colectomy and proctectomy procedure targeted modules. Postdischarge venous thromboembolism included pulmonary embolism or deep vein thrombosis diagnosed after discharge from the index hospitalization. Multivariable logistic regression estimated the association of patient/operative factors with postdischarge venous thromboembolism. A postdischarge venous thromboembolism risk calculator was subsequently constructed.

      Results

      Of 18,990 patients, 199 (1.1%) developed a postdischarge venous thromboembolism within the first 30 postoperative days. Preoperative factors associated with postdischarge venous thromboembolism included body mass index (1.9% with body mass index ≥35 vs 0.8% with body mass index 18.5–24.9; odds ratio 2.34 [95% confidence interval 1.49–3.67]), steroid use (1.3% vs 0.7%; odds ratio 1.91 [95% confidence interval 1.37–2.66]), and ulcerative colitis (1.5% vs 0.8% with Crohn’s disease; odds ratio 1.76 [95% confidence interval 1.32–2.34]). Minimally invasive surgery was associated with postdischarge venous thromboembolism (1.2% vs 0.9% with open; odds ratio 1.42 [95% confidence interval 1.05–1.92]), as was anastomotic leak (2.8% vs 1.0%; odds ratio 2.24 [95% confidence interval 1.31–3.83]) and ileus (2.1% vs 0.9%; odds ratio 2.60 [95% confidence interval 1.91–3.54]). The predicted probability of postdischarge venous thromboembolism ranged from 0.2% to 14.3% based on individual risk factors.

      Conclusion

      Preoperative, intraoperative, and postoperative factors are associated with postdischarge venous thromboembolism after an operation for inflammatory bowel disease. A postdischarge venous thromboembolism risk calculator was developed which can be used to tailor extended venous thromboembolism chemoprophylaxis by individual risk.

      Introduction

      Despite the preventable nature of venous thromboembolism (VTE), pulmonary embolism (PE), and deep vein thrombosis (DVT), VTE remains a leading cause of morbidity and mortality.
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      Thus, we sought (1) to identify preoperative, intraoperative, and postoperative risk factors associated with postdischarge VTE in a national cohort of patients undergoing colectomy or proctectomy for IBD and (2) to develop a postdischarge VTE risk calculator to identify high-risk patients for extended chemoprophylaxis.

      Methods

      Data source and patient population

      Patients who underwent colon or rectal resection between January 1, 2012 and December 31, 2018 were identified from the colectomy and proctectomy procedure targeted participant use data files of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). The ACS NSQIP is a validated, prospective registry of a sample of patients undergoing select operations at participating hospitals.
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      Beginning in 2012, procedure-specific modules were developed for various organ systems, including colectomy and proctectomy. These modules allow for abstraction of additional procedure specific variables, inclusive of preoperative workup and additional postoperative complications.
      Patients with an International Classification of Diseases versions 9 or 10 code corresponding to a diagnosis of IBD and a Current Procedural Terminology code corresponding to partial or total colectomy or proctectomy were included for analysis. Exclusions included patients with a duration of stay exceeding 30 days, those diagnosed with an inpatient VTE, or who suffered an inpatient death.

      Primary outcome and predictors

      Postdischarge VTE included either PE or DVT diagnosed after the date of index hospitalization discharge but within 30 days of operative resection. Per ACS NSQIP definitions, the diagnosis of a PE required a new diagnosis of a blood clot in a pulmonary artery identified on imaging, and the diagnosis of a DVT required a new diagnosis of a blood clot or thrombus in the venous system identified on imaging and for which therapeutic anticoagulation was either recommended or administered. Accordingly, mesenteric and portal venous thrombosis are included within the definition of DVT.
      A review of the literature was undertaken to identify potential preoperative, intraoperative, and postoperative factors associated with postdischarge VTE. Key preoperative factors included age, sex, race, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared [kg/m2] and categorized as underweight <18.5, normal weight 18.5–24.9, overweight 25.0–29.9, obese 30.0–34.9, and morbidly obese ≥35.0), select preoperative comorbidities, functional status as determined by the American Society of Anesthesiologists classification, preoperative labs inclusive of albumin and platelet count, and indication for operative indication (Crohn’s disease or ulcerative colitis); there were no available variables to determine the severity or duration of IBD in this database. Intraoperative factors evaluated for association with postdischarge VTE included the classification as an emergency operation, operative time, procedure type categorized as (1) ileocecectomy, (2) partial or total colectomy, or (3) proctectomy with or without colectomy, and operative approach (open or minimally invasive). Patients who underwent minimally invasive operations that were converted to open were classified as open. Postoperative factors evaluated for association with postdischarge VTE included anastomotic leak, ileus, surgical site infection (including superficial, deep, and organ space infections), pneumonia, reintubation, renal failure, transfusion, reoperation, and duration of hospital stay. Only those complications that were diagnosed during the index hospitalization were included for analysis. Undated complications derived from the colectomy and proctectomy procedure targeted data were reviewed for readmission International Classification of Diseases versions 9 and 10 codes potentially related to these conditions. Patients who were readmitted with a corresponding diagnosis were not considered to have had that diagnosis at hospital discharge, and therefore, those complications were not included in analyses.

      Statistical analysis

      The overall rate of VTE was reported as inpatient and postdischarge VTEs. The frequency of postdischarge VTE based on preoperative, intraoperative, and postoperative factors was evaluated on bivariate analysis using separate χ2 tests for categorical variables and t tests for continuous variables. Factors with statistically significant associations on bivariate analyses based on a predetermined P < .05 were entered into a multivariable logistic regression model, with collinear predictors removed progressively via forward selection until a final model was estimated. Model diagnostics evaluating discrimination and calibration included the C-statistic and Hosmer and Lemeshow (HL) χ2, respectively. A Hosmer and Lemeshow chi-squared value with a P < .05 indicates poor calibration.
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      Internal validation was performed using 20 iterations of 10-fold cross validation, with model diagnostics averaged over each iteration.
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      • Hu J.
      K-fold averaging cross-vaidation procedure.
      The final regression model was estimated on the logit scale and used to generate a risk calculator. Beta coefficients corresponding to the individual risk factors for each patient were summed with the model intercept, equaling the log probability (LP) of the outcome (postdischarge VTE) for each patient. Next, the LP was exponentiated to generate the predicted probability of postdischarge VTE for each patient using the following equation: probability of event = exp(LP)/(1+exp[LP]).
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      Predicted probabilities were plotted for the entire cohort to demonstrate variation in postdischarge VTE risk.
      All statistical analyses were completed in Stata version 14.2 (Stata Corp, College Station, TX). This study was determined to be exempt from review by the Institutional Review Board at Northwestern University based on use of deidentified data.

      Results

      Cohort description

      Of 19,695 patients who underwent colectomy or proctectomy for IBD, 538 (2.7%) developed a VTE, 339 (63.0%) of whom were diagnosed during inpatient recovery and 199 (37.0%) after hospital discharge. After excluding 295 patients with a length of stay greater than 30 days, 294 patients who developed an inpatient VTE, and 116 who suffered an inpatient death, a total of 18,990 patients at risk for postdischarge VTE were included for final analyses. The postdischarge VTE rate was 1.1%. The mean patient age was 42.7 years, 50.4% of patients were female, and 80.0% were White. Of the analyzed patients, 43.4% had a normal BMI, 63.5% were on preoperative steroids, and 66.0% had a diagnosis of Crohn’s disease. The most common procedure was an ileocecectomy (40.0%), and the majority of cases were performed via a minimally invasive approach (55.5%). The most common postoperative complication was ileus, which occurred in 15.5% of patients. Among patients who developed a postdischarge VTE, 155 were readmitted within 30 days of the index operation (77.9% vs 13.6% of patients who did not develop a postdischarge VTE; P < .001). Additional demographic information is listed in Table I.
      Table IGeneral cohort characteristics of patients undergoing colorectal resection for inflammatory bowel disease
      Patient characteristic (N = 18,990)n (%)
      Preoperative factors
      Age, y, mean (SD)42.7 (16.2)
      Sex
       Male9,413 (49.6)
       Female9,577 (50.4)
      Race
       White15,197 (80.0)
       Black1,315 (6.9)
       Asian243 (1.3)
       Other/not reported2,235 (11.8)
      BMI
       <18.51,514 (8.1)
       18.5–24.98,130 (43.4)
       25.0–29.95,116 (27.3)
       30.0–34.92,469 (13.2)
       ≥35.01,505 (8.0)
      Comorbidities
       Bleeding disorder542 (2.9)
       Dyspnea (moderate exertion/rest)480 (2.5)
       Hypertension3,226 (17.0)
       Diabetes924 (4.9)
       Steroid use12,049 (63.5)
       Weight loss >10% in past 6 months1,954 (10.3)
      Functional status
       Independent18,804 (99.1)
       Dependent163 (0.9)
      ASA Class
       I/II10,686 (56.3)
       III/IV/V8,284 (43.7)
      Preoperative albumin <3 g/dL3,282 (22.8)
      Preoperative platelet count
       <150,000546 (3.1)
       150,000–400,00013,357 (74.8)
       >400,0003,951 (22.1)
      Operative indication
       Crohn’s disease12,540 (66.0)
       Ulcerative colitis6,450 (34.0)
      Intraoperative factors
      Emergency case classification1,351 (7.1)
      Operative time, min, mean (SD)191.1 (93.4)
      Procedure type
       Ileocecectomy7,586 (40.0)
       Colectomy7,435 (39.2)
       Proctectomy +/– colectomy3,969 (20.9)
      Operative approach
       Open8,445 (44.5)
       Minimally invasive10,545 (55.5)
      Postoperative factors
      Inpatient postoperative complications
       Anastomotic leak568 (3.0)
       Ileus2,940 (15.5)
       SSI1,008 (5.3)
       Pneumonia175 (0.9)
       Reintubation94 (0.5)
       Renal failure57 (0.3)
       Transfusion1,756 (9.3)
       Reoperation519 (2.7)
      Length of stay, d, mean, (SD)6.3 (4.3)
      Outcomes
      Postdischarge DVT173 (0.9)
      Postdischarge PE36 (0.2)
      Any postdischarge VTE199 (1.1)
      ASA, American Society of Anesthesiologists; COPD, chronic obstructive pulmonary disease; SSI, surgical site infection.

      Factors associated with postdischarge VTE

      Several preoperative factors were associated with postdischarge VTE. IBD patients with BMI in the obese and morbidly obese categories more frequently developed postdischarge VTEs after colectomy or proctectomy than patients with normal BMIs (1.4% if BMI 30.0–34.9; odds ratio [OR] 1.74 [95% confidence interval (CI) 1.15–2.63; P = .009], 1.9% if BMI ≥35.0; OR 2.34 [95% CI 1.49–3.67]; P < .001 vs 0.8% if BMI 18.5–24.9). Preoperative steroid use was also associated with postdischarge VTE (1.3% vs 0.7%; OR 1.91 [95% CI 1.37–2.66]; P < .001), as was a diagnosis of ulcerative colitis as compared with Crohn’s disease (1.5% vs 0.8%, OR 1.76 [95% CI 1.32–2.34]; P < .001). There were no differences in the frequency of postdischarge VTE diagnosis based on other preoperative patient factors (Table II).
      Table IICharacteristics of patients who develop postdischarge VTE after IBD surgery
      Total patients N = 18,990No pdVTEpdVTEP value
      n (%)
      18,791 (99.0)199 (1.1)
      Preoperative factors
      Age, y
       <304,963 (99.1)47 (0.9).549
       30–404,226 (98.8)50 (1.2)
       40–554,695 (99.1)45 (1.0)
       ≥554,907 (98.9)57 (1.2)
      Sex
       Male9,315 (99.0)98 (1.0).927
       Female9,476 (99.0)101 (1.1)
      Race
       White15,030 (98.9)167 (1.1).562
       Black1,305 (99.2)10 (0.8)
       Asian241 (99.2)2 (0.8)
       Other/not reported2,215 (99.1)20 (0.9)
      BMI
       <18.51,504 (99.3)10 (0.7)<.001
       18.5–24.98,065 (99.2)65 (0.8)
       25.0–29.95,057 (98.9)59 (1.2)
       30.0–34.92,434 (98.6)35 (1.4)
       ≥35.01,477 (98.1)28 (1.9)
      Comorbidities
       Bleeding disorder535 (98.7)7 (1.3).572
       Dyspnea (moderate exertion/rest)476 (99.2)4 (0.8).640
       Hypertension3,194 (99.0)32 (1.0).732
       Diabetes916 (99.1)8 (0.9).577
       Steroid use11,897 (98.7)152 (1.3)<.001
       Weight loss >10% in past 6 months1,935 (99.0)19 (1.0).729
      Functional status
       Independent18,607 (99.0)197 (1.1).823
       Dependent161 (98.8)2 (1.2)
      ASA Class
       I/II10,585 (99.1)101 (1.0).129
       III/IV/V8,187 (98.8)97 (1.2)
      Preoperative albumin <3 g/dL3,241 (98.8)41 (1.3).252
      Preoperative platelet count
       <150,000540 (98.9)6 (1.1).978
       150,000–400,00013,218 (99.0)139 (1.0)
       >400,0003,911 (99.0)40 (1.0)
      Operative indication
       Crohn’s disease12,438 (99.2)102 (0.8)<.001
       Ulcerative colitis6,353 (98.5)97 (1.5)
      Intraoperative factors
      Emergency case classification1,334 (98.7)17 (1.3).431
      Operative time, h
       <24,089 (99.3)28 (0.7).049
       2–35,938 (99.0)63 (1.1)
       3–44,250 (98.8)52 (1.2)
       >44,511 (98.8)56 (1.2)
      Procedure type
       Ileocectomy7,529 (99.3)57 (0.8).005
       Colectomy7,343 (98.8)92 (1.2)
       Proctectomy3,919 (98.7)50 (1.3)
      Operative approach
       Open8,374 (99.2)72 (0.9).018
       Minimally invasive10,417 (98.8)127 (1.2)
      Postoperative factors
      Inpatient postoperative complications
       Anastomotic leak552 (97.2)16 (2.8)<.001
       Ileus2,879 (97.9)61 (2.1)<.001
       SSI1,000 (99.2)8 (0.8).415
       Pneumonia172 (98.3)3 (1.7).384
       Reintubation92 (97.9)2 (2.1).303
       Renal failure56 (98.3)1 (1.8).600
       Transfusion1,730 (98.5)26 (1.5).062
       Reoperation511 (98.5)8 (1.5).263
      Length of stay, d
       <44,335 (99.0)43 (1.0).926
       4–53,580 (99.0)37 (1.0)
       5–74,844 (98.9)55 (1.1)
       ≥76,032 (99.0)64 (1.1)
      ASA, American Society of Anesthesiologists; COPD, chronic obstructive pulmonary disease; pdVTE, post-discharge venous thromboembolism; SSI, skin/soft tissue infection.
      Intraoperative factors with increased postdischarge VTE rates included greater operative times (eg, 1.2% of patients with operative time >4 hours vs 0.7% <2 hours; P = .049), type of operations (1.3% of patients undergoing proctectomy, 1.2% colectomy vs 0.8% ileocecectomy; P = .005), and operative approach (1.2% of patients after minimally invasive surgery vs 0.9% open; P = .018). These factors were collinear, and operative approach remained statistically significant in the final adjusted model (OR 1.42 [95% CI 1.05–1.92], P = .022 Table III). With regard to postoperative complications, both anastomotic leak (2.8% vs 1.0%; OR 2.24 [95% CI 1.31–3.83], P = .003) and postoperative ileus (2.1% vs 0.9%; OR 2.60 [95% CI 1.91–3.54], P < .001) were associated with postdischarge VTE. Other postoperative complications were not associated with postdischarge VTE nor was postoperative hospital length of stay (Table II).
      Table IIIAssociation between patient characteristics and postdischarge VTE after IBD surgery
      Adjusted OR (95% CI)P value
      BMI
       <18.50.80 (0.41–1.57).520
       18.5–24.91.00REF
       25.0–29.91.42 (1.00–2.03).051
       30.0–34.91.74 (1.15–2.63).009
       ≥352.34 (1.49–3.67)<.001
      Preoperative steroids
       No1.00REF
       Yes1.91 (1.37–2.66)<.001
      IBD type
       Crohn’s disease1.00REF
       Ulcerative colitis1.76 (1.32–2.34)<.001
      Operative approach
       Open1.00REF
       MIS1.42 (1.05–1.92).022
      Anastomotic leak
       No1.00REF
       Yes2.24 (1.31–3.83).003
      Postoperative ileus
       No1.00REF
       Yes2.60 (1.91–3.54)<.001
      MIS, minimally invasive surgery; REF, reference.

      Postdischarge VTE risk calculator

      Beta coefficients for preoperative, intraoperative, and postoperative factors associated with postdischarge VTE are listed in Supplemental Table I along with the model constant for use as a postdischarge VTE risk calculator. Using the calculator, the predicted probability of postdischarge VTE ranged from 0.2% to 14.3% (Fig 1); 40.6% of patients had a postdischarge VTE risk of 1.0% or greater, and 10.2% of patients had a risk of 2.0% or greater. The model’s C-statistic was 0.691 and HL χ2 P = .336 demonstrating good discrimination and calibration. Internal validation via 20 iterations of 10-fold cross validation yielded a mean C-statistic of 0.665.
      Figure thumbnail gr1
      Fig 1Predicted probability of postdischarge VTE after IBD surgery.

      Discussion

      VTE risk is increased after many types of operations and extends beyond hospital discharge. In particular, patients undergoing specific types of operations, such as major orthopedic, bariatric, and abdominal or pelvic operations, or IBD resections have a notable risk of postdischarge VTE.
      • Shah D.R.
      • Wang H.
      • Bold R.J.
      • et al.
      Nomograms to predict risk of in-hospital and post-discharge venous thromboembolism after abdominal and thoracic surgery: an American College of Surgeons National Surgical Quality Improvement Program analysis.
      ,
      • Alhassan N.
      • Trepanier M.
      • Sabapathy C.
      • et al.
      Risk factors for post-discharge venous thromboembolism in patients undergoing colorectal resection: a NSQIP analysis.
      ,
      • Clark L.N.
      • Helm M.C.
      • Gould J.C.
      Practice patterns regarding post-discharge chemoprophylaxis for venous thromboembolism following bariatric surgery in the United States.
      • Flevas D.A.
      • Megaloikonomos P.D.
      • Dimopoulos L.
      • Mitsiokapa E.
      • Koulouvaris P.
      • Mavrogenis A.F.
      Thromboembolism prophylaxis in orthopaedics: an update.
      • Schlick C.J.R.
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      • Yang A.D.
      • Bentrem D.J.
      Post-discharge venous thromboembolism after pancreatectomy for malignancy: predicting risk based on preoperative, intraoperative, and postoperative factors [e-pub ahead of print].
      Although clinical practice guidelines recommend extended chemoprophylaxis for high-risk patients postoperatively, identifying those high-risk patients remains difficult. Using only information available at hospital discharge, we identified preoperative, intraoperative, and postoperative factors associated with postdischarge VTE in patients undergoing colorectal resection for IBD. BMI, preoperative steroid use, IBD type, operative approach, and inpatient postoperative diagnoses of anastomotic leak and ileus were associated with postdischarge VTE. A postdischarge risk calculator was constructed to quantify relative risk based upon these factors and individual patient’s predicted risk ranged from 0.2% to 14.3%.

      Overall VTE Risk

      Overall, 2.7% of patients developed a VTE after a colon or rectal resection for IBD, of whom 37.0% were diagnosed after hospital discharge for a postdischarge VTE rate of 1.1%. These findings are consistent with previous evaluations of VTE after operations for IBD, with overall VTE rates of approximately 2.5% and with 40% of the events occurring after hospital discharge.
      • Benlice C.
      • Holubar S.D.
      • Gorgun E.
      • et al.
      Extended venous thromboembolism prophylaxis after elective surgery for IBD patients: nomogram-based risk assessment and prediction from nationwide cohort.
      ,
      • Wallaert J.B.
      • De Martino R.R.
      • Marsicovetere P.S.
      • et al.
      Venous thromboembolism after surgery for inflammatory bowel disease: are there modifiable risk factors? Data from ACS NSQIP.
      ,
      • Wilson M.Z.
      • Connelly T.M.
      • Tinsley A.
      • Hollenbeak C.S.
      • Koltun W.A.
      • Messaris E.
      Ulcerative colitis is associated with an increased risk of venous thromboembolism in the postoperative period: the results of a matched cohort analysis.
      Furthermore, these rates are notably greater than VTE rates in patients undergoing colorectal resection for benign indications.
      • Alhassan N.
      • Trepanier M.
      • Sabapathy C.
      • et al.
      Risk factors for post-discharge venous thromboembolism in patients undergoing colorectal resection: a NSQIP analysis.
      ,
      • Wilson M.Z.
      • Connelly T.M.
      • Tinsley A.
      • Hollenbeak C.S.
      • Koltun W.A.
      • Messaris E.
      Ulcerative colitis is associated with an increased risk of venous thromboembolism in the postoperative period: the results of a matched cohort analysis.

      Factors Associated with Post-Discharge VTE

      Preoperative, intraoperative, and postoperative factors were associated with postdischarge VTE in this study of patients undergoing colon or rectal resection for IBD. Patients with an obese BMI had a 74% relative increased odds of postdischarge VTE, while those with morbidly obese BMIs had a greater than 2-fold relative increased odds of postdischarge VTE. These findings are consistent with previous reports of the association between BMI and VTE in postoperative IBD patient
      • Merrill A.
      • Millham F.
      Increased risk of postoperative deep vein thrombosis and pulmonary embolism in patients with inflammatory bowel disease: a study of National Surgical Quality Improvement Program patients.
      However, our study is somewhat unique, because no prior study has identified an association between BMI and postdischarge VTE in postoperative IBD patients, despite evidence that BMI is associated with postdischarge VTE in abdominal malignancies and patients undergoing colon or rectal resection for other indications.
      • Alhassan N.
      • Trepanier M.
      • Sabapathy C.
      • et al.
      Risk factors for post-discharge venous thromboembolism in patients undergoing colorectal resection: a NSQIP analysis.
      ,
      • Schlick C.J.R.
      • Liu J.Y.
      • Yang A.D.
      • Bentrem D.J.
      • Bilimoria K.Y.
      • Merkow R.P.
      Pre-operative, intra-operative, and post-operative factors associated with post-discharge venous thromboembolism following colorectal cancer resection.
      ,
      • Beal E.W.
      • Tumin D.
      • Chakedis J.
      • et al.
      Which patients require extended thromboprophylaxis after colectomy? Modeling risk and assessing indications for post-discharge pharmacoprophylaxis.
      ,
      • Parkin L.
      • Sweetland S.
      • Balkwill A.
      • et al.
      Body mass index, surgery, and risk of venous thromboembolism in middle-aged women: a cohort study.
      Preoperative steroid use was also associated with postdischarge VTE, which has been previously demonstrated.
      • Benlice C.
      • Holubar S.D.
      • Gorgun E.
      • et al.
      Extended venous thromboembolism prophylaxis after elective surgery for IBD patients: nomogram-based risk assessment and prediction from nationwide cohort.
      ,
      • McKenna N.P.
      • Behm K.T.
      • Ubl D.S.
      • et al.
      Analysis of postoperative venous thromboembolism in patients with chronic ulcerative colitis: is it the disease or the operation?.
      This association could be a surrogate for severe forms of IBD or acute inflammation, which are known to increase VTE risk
      • Andrade A.R.
      • Barros L.L.
      • Azevedo M.F.C.
      • et al.
      Risk of thrombosis and mortality in inflammatory bowel disease.
      ,
      • Alkim H.
      • Koksal A.R.
      • Boga S.
      • Sen I.
      • Alkim C.
      Etiopathogenesis, prevention, and treatment of thromboembolism in inflammatory bowel disease.
      ; exogenous steroid use, however, is associated with VTEs, regardless of indication, which may be related to increased production of clotting factors.
      • Johannesdottir S.A.
      • Horvath-Puho E.
      • Dekkers O.M.
      • et al.
      Use of glucocorticoids and risk of venous thromboembolism: a nationwide population-based case-control study.
      Patients with ulcerative colitis in our study had a 76% relative increased odds of postdischarge VTE compared with patients with Crohn’s disease, as has been reported in other studies.
      • Wallaert J.B.
      • De Martino R.R.
      • Marsicovetere P.S.
      • et al.
      Venous thromboembolism after surgery for inflammatory bowel disease: are there modifiable risk factors? Data from ACS NSQIP.
      ,
      • Wilson M.Z.
      • Connelly T.M.
      • Tinsley A.
      • Hollenbeak C.S.
      • Koltun W.A.
      • Messaris E.
      Ulcerative colitis is associated with an increased risk of venous thromboembolism in the postoperative period: the results of a matched cohort analysis.
      ,
      • Moghadamyeghaneh Z.
      • Hanna M.H.
      • Carmichael J.C.
      • Nguyen N.T.
      • Stamos M.J.
      A nationwide analysis of postoperative deep vein thrombosis and pulmonary embolism in colon and rectal surgery.
      ,
      • Scarpa M.
      • Pilon F.
      • Pengo V.
      • et al.
      Deep venous thrombosis after surgery for inflammatory bowel disease: is standard dose low molecular weight heparin prophylaxis enough?.
      Similar to steroid use, it has been hypothesized that this association could be related to inflammation severity and resultant alterations to the coagulation cascade in IBD.
      • Jackson L.M.
      • O’Gorman P.J.
      • O’Connell J.
      • Cronin C.C.
      • Cotter K.P.
      • Shanahan F.
      Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden.
      • Saibeni S.
      • Bottasso B.
      • Spina L.
      • et al.
      Assessment of thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels in inflammatory bowel diseases.
      • Saibeni S.
      • Cattaneo M.
      • Vecchi M.
      • et al.
      Low vitamin B(6) plasma levels, a risk factor for thrombosis, in inflammatory bowel disease: role of inflammation and correlation with acute phase reactants.
      Because ulcerative colitis is a contiguous inflammatory condition, a greater inflammatory response may be seen in these patients compared with the isolated and/or sporadic inflammation seen in Crohn’s disease. Patients undergoing restorative proctocolectomy for ulcerative colitis can be particularly susceptible to portal venous thrombosis, which may arise, in part, from mesenteric stretching and tension during ileoanal pouch creation.
      • Remzi F.H.
      • Fazio V.W.
      • Oncel M.
      • et al.
      Portal vein thrombi after restorative proctocolectomy.
      Furthermore, patients with Crohn’s disease often require resection for fibrostenotic disease, which is thought to be a noninflamed sequela of quiescent inflammation.
      • Chang C.W.
      • Wong J.M.
      • Tung C.C.
      • Shih I.L.
      • Wang H.Y.
      • Wei S.C.
      Intestinal stricture in Crohn's disease.
      ,
      • Li J.
      • Mao R.
      • Kurada S.
      • et al.
      Pathogenesis of fibrostenosing Crohn's disease.
      Several intraoperative factors were associated with postdischarge VTE on bivariate analyses, including operative time, type of procedure, and operative approach. In constructing a multivariable adjusted model, these factors were collinear, with operative approach generating the best model fit. Our finding that minimally invasive operative approaches are associated with postdischarge VTE is contrary to prior work indicating that minimally invasive surgery is associated with inpatient VTE in postoperative IBD patients but not postdischarge VTE.
      • Benlice C.
      • Holubar S.D.
      • Gorgun E.
      • et al.
      Extended venous thromboembolism prophylaxis after elective surgery for IBD patients: nomogram-based risk assessment and prediction from nationwide cohort.
      A prior NSQIP analysis of patients undergoing colorectal resection for IBD, however, did identify findings consistent with our study that minimally invasive surgery is associated with a decreased odds of inpatient VTE, but an increased odds of postdischarge VTE.
      • Alhassan N.
      • Trepanier M.
      • Sabapathy C.
      • et al.
      Risk factors for post-discharge venous thromboembolism in patients undergoing colorectal resection: a NSQIP analysis.
      This finding could be related to a time bias, because patients who undergo minimally invasive colon operations are discharged typically sooner, which may shift the distribution of VTE diagnoses from the inpatient setting to outpatient.
      • Alizadeh R.F.
      • Chaudhury H.H.
      • Li S.
      • et al.
      Ileocolic resection for Crohn's disease: a minimally invasive approach claims its place.
      Alternatively, providers may be less likely to prescribe postdischarge chemoprophylaxis to patients undergoing minimally invasive surgery because of a perceived decreased risk of VTE; however, VTE rates may be as high as 10% in ultrasonographically screened patients after laparoscopic colon resections.
      • Vedovati M.C.
      • Becattini C.
      • Rondelli F.
      • et al.
      A randomized study on 1-week versus 4-week prophylaxis for venous thromboembolism after laparoscopic surgery for colorectal cancer.
      Finally, inpatient diagnoses of postoperative ileus and anastomotic leak were associated with postdischarge VTE. Previous studies have identified that postoperative complications typically compound after colorectal surgery, with complications being the greatest risk factors for postdischarge VTE.
      • Alhassan N.
      • Trepanier M.
      • Sabapathy C.
      • et al.
      Risk factors for post-discharge venous thromboembolism in patients undergoing colorectal resection: a NSQIP analysis.
      ,
      • Tevis S.E.
      • Kennedy G.D.
      Postoperative complications: looking forward to a safer future.
      Specifically, postoperative ileus has been identified as a high-risk complication associated with VTE after laparoscopic colon resection.
      • Kronberg U.
      • Kiran R.P.
      • Soliman M.S.
      • et al.
      A characterization of factors determining postoperative ileus after laparoscopic colectomy enables the generation of a novel predictive score.
      Furthermore, both anastomotic leak and ileus have been identified as risk factors for postdischarge VTE in patients undergoing resection for colorectal cancer.
      • Schlick C.J.R.
      • Liu J.Y.
      • Yang A.D.
      • Bentrem D.J.
      • Bilimoria K.Y.
      • Merkow R.P.
      Pre-operative, intra-operative, and post-operative factors associated with post-discharge venous thromboembolism following colorectal cancer resection.
      Thus, despite no prior study to the best of our knowledge that has identified an association between anastomotic leak or postoperative ileus and postdischarge VTE in patients undergoing colon or rectal surgery for IBD, our findings are not surprising.

      Postdischarge VTE risk calculator

      Although randomized controlled trials have shown the benefit of extended chemoprophylaxis in high-risk patients, such as those undergoing abdominal or pelvic resection for cancer, no such trials have been performed after IBD surgery.
      • Bergqvist D.
      • Agnelli G.
      • Cohen A.T.
      • et al.
      and the ENOXACAN II Investigators
      Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer.
      • Kakkar V.V.
      • Balibrea J.L.
      • Martinez-Gonzalez J.
      • Prandoni P.
      CANBESURE Study Group
      Extended prophylaxis with bemiparin for the prevention of venous thromboembolism after abdominal or pelvic surgery for cancer: the CANBESURE randomized study.
      • Rasmussen M.S.
      • Jorgensen L.N.
      • Wille-Jorgensen P.
      Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery.
      Clinical practice guidelines including those put forward by the American Society of Colon and Rectal Surgeons recommend extended chemoprophylaxis in high-risk patients as defined as a 6% risk of overall VTE by the American College of Chest Physicians guidelines.
      • Gould M.K.
      • Garcia D.A.
      • Wren S.M.
      • et al.
      Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
      ,
      • Fleming F.
      • Gaertner W.
      • Ternent C.A.
      • et al.
      The American Society of Colon and Rectal Surgeons Clinical Practice Guideline for the Prevention of Venous Thromboembolic Disease in Colorectal Surgery.
      The overall rate of VTE in our study is well below 6%, thus identification of risk factors known at the time of discharge that are associated with postdischarge VTE in patients undergoing IBD surgery is warranted to best select patients for extended chemoprophylaxis.
      Prior tools to risk stratifying these patients have been limited. The Caprini score was developed to estimate overall VTE risk in postoperative patients after major operations,
      • Bahl V.
      • Hu H.M.
      • Henke P.K.
      • Wakefield T.W.
      • Campbell Jr., D.A.
      • Caprini J.A.
      A validation study of a retrospective venous thromboembolism risk scoring method.
      ,
      • Caprini J.A.
      Thrombosis risk assessment as a guide to quality patient care.
      but the Caprini score cannot discriminate between inpatient and postdischarge VTEs, does not include postoperative complications, and identifies the same risk for patients with ulcerative colitis and Crohn’s disease. A VTE risk calculator for IBD patients has also been developed, but this calculator is not specific to postoperative patients, who have a different risk profile than patients admitted for IBD who do not require operative treatment.
      • McCurdy J.D.
      • Israel A.
      • Hasan M.
      • et al.
      A clinical predictive model for post-hospitalisation venous thromboembolism in patients with inflammatory bowel disease.
      While Benlice et al developed a nomogram to indicate risk for postdischarge VTE in IBD patients, their nomogram relies on just 3 statistically significant risk factors, none of which are from the postoperative period.
      • Benlice C.
      • Holubar S.D.
      • Gorgun E.
      • et al.
      Extended venous thromboembolism prophylaxis after elective surgery for IBD patients: nomogram-based risk assessment and prediction from nationwide cohort.
      The risk calculator described in our study was developed using the same methodology that has been used in other ACS NSQIP calculators, includes variables from all phases of care, and has good internal validity. Thus, the calculator we offer can help providers to indicate high-risk patients who may derive the greatest benefit from extended VTE chemoprophylaxis after colon or rectal resection for IBD.
      An example application of the postdischarge VTE risk calculator from the study population is as follows: a 50-year-old woman with a BMI of 28.4 on preoperative steroids for ulcerative colitis underwent an open protocolectomy with ileopouch anal anastomosis and diverting loop ileostomy. Her postoperative course was complicated by anastomotic leak and postoperative ileus, which were managed conservatively. She was discharged from the hospital on postoperative day 9. Thus, her risk factors for postdischarge VTE as identified in this study include an overweight BMI (beta coefficient 0.35), preoperative steroids (beta coefficient 0.65), ulcerative colitis (beta coefficient 0.57), an open operation (beta coefficient 0.00), anastomotic leak (beta coefficient 0.81), and postoperative ileus (beta coefficient 0.95). By summing the listed beta coefficients (3.33) with the model intercept (–5.97), the LP of postdischarge VTE is calculated as –2.64. The event probability is then calculated as exp(LP)/(1+exp[LP]) = 6.7%, we would suggest that this risk would warrant extended postdischarge prophylaxis for VTE.
      Although prospective studies have not identified a specific postdischarge VTE risk threshold above which postoperative IBD patients should receive postdischarge VTE prophylaxis, the postdischarge VTE risk generated by this calculator can be interpreted within the context of current guidelines and cost-effectiveness analyses. For example, the American College of Chest Physician guidelines define high-risk patients as those with an overall VTE risk >6%.
      • Gould M.K.
      • Garcia D.A.
      • Wren S.M.
      • et al.
      Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
      Considering that approximately 40% of postoperative VTEs are diagnosed in the postdischarge setting, high-risk could be defined as >2.4%.
      • Benlice C.
      • Holubar S.D.
      • Gorgun E.
      • et al.
      Extended venous thromboembolism prophylaxis after elective surgery for IBD patients: nomogram-based risk assessment and prediction from nationwide cohort.
      ,
      • Wilson M.Z.
      • Connelly T.M.
      • Tinsley A.
      • Hollenbeak C.S.
      • Koltun W.A.
      • Messaris E.
      Ulcerative colitis is associated with an increased risk of venous thromboembolism in the postoperative period: the results of a matched cohort analysis.
      Similarly, a cost-effectiveness analysis of postdischarge chemoprophylaxis in patients after abdominal oncologic resections identified a threshold of 2.4%, above which postdischarge chemoprophylaxis was the dominant strategy.
      • Iannuzzi J.C.
      • Rickles A.S.
      • Kelly K.N.
      • et al.
      Defining high risk: cost-effectiveness of extended-duration thromboprophylaxis following major oncologic abdominal surgery.
      The cost effectiveness of postdischarge chemoprophylaxis after operative resection of Crohn’s disease, however, favored selective prescribing at risk thresholds >4.9%.
      • Leeds I.L.
      • DiBrito S.R.
      • Canner J.K.
      • Haut E.R.
      • Safar B.
      Cost-benefit limitations of extended, outpatient venous thromboembolism prophylaxis following surgery for Crohn's disease.
      Specific decisions regarding postdischarge prophylaxis should be made within the context of the provider and patient’s risk aversion, and a calculated relative risk of postdischarge VTE will aide in that decision making process.

      Limitations

      First, ACS NSQIP contains observational data from which association but not causation can be derived. Second, some individual factors, such as prothrombotic gene mutations, severity of disease, and duration of IBD symptoms, may be associated with VTE risk but are not available in ACS NSQIP, and thus were not included in this study. Third, there is no information available in ACS NSQIP regarding prophylaxis compliance, including chemoprophylaxis during the inpatient setting, which has been demonstrated to decrease VTE rates. Furthermore, there are no data available regarding prescribing or compliance of extended chemoprophylaxis. Thus, the calculated VTE rates are not adjusted for the use of inpatient or postdischarge prophylaxis, and the true VTE rates in the absence of prophylaxis are unknown; however, prescription rates of postdischarge chemoprophylaxis are approximately 10% after IBD surgery, thus the majority of patients in this study likely did not receive postdischarge chemoprophylaxis.
      • Mukkamala A.
      • Montgomery J.R.
      • De Roo A.C.
      • Ogilvie Jr., J.W.
      • Regenbogen S.E.
      Population-based analysis of adherence to post-discharge extended VTE prophylaxis after colorectal resection [e-pub ahead of print].
      Fourth, the postoperative risk of VTE extends beyond 30 days, but we were only able to evaluate 30-day outcome data in this study based on data collection techniques used by ACS NSQIP. Fifth, surveillance strategies are not included in the ACS NSQIP data. We are unable to evaluate for asymptomatic VTEs diagnosed via screening, which would be documented VTEs within the ACS NSQIP data but are of unclear clinical significance. Additionally, given the increased baseline risk of VTE in IBD patients, it is unclear how many, if any, of the described VTEs were present preoperatively. Finally, a time bias may exist in this study in that patients with greater inpatient durations of stay have a shorter period at risk of postdischarge VTE within the 30-day collection period of ACS NSQIP. However, these data limitations likely will not change the risk factors associated with postdischarge VTE identified in this study but may underestimate the true postdischarge VTE risk.
      In conclusion, overall, 2.7% of patients developed a VTE after colon or rectal resection for IBD, with 1.1% of patients diagnosed after hospital discharge. Patient-specific risk factors associated with postdischarge VTE include BMI, steroid use, IBD type, operative approach, anastomotic leak, and ileus. A postdischarge VTE risk calculator was constructed and can be used to identify high-risk patients at the time of discharge who merit extended chemoprophylaxis after colon or rectal resection for IBD.

      Funding/Support

      TKY is supported by the Agency for Healthcare Research and Quality (5T32HS000078); ADY by the National Heart, Lung and Blood Institute (K08NIHL145139); DJB by a Veteran’s Administration Merit Award (I01HX002290); KYB by the Agency for Healthcare Research and Quality (R01HS024516); and RPM by the Agency for Healthcare Research and Quality (K12HS026385) and an Institutional Research Grant from the American Cancer Society (IRG-18-163-24).

      Conflict of interest/Disclosures

      None declared.

      Supplementary data

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