A total of 1,466 patients with GI disease admitted to Asahikawa Medical University Hospital from January 2009 to December 2013 and who underwent contrast-enhanced CT (CECT) and/or ultrasonography (US) at least once were enrolled. Of these, 340 patients with IBD (89 with UC, 251 with CD), 557 patients with GI cancer (esophageal cancer, gastric cancer, colon cancer and small intestinal cancer), and 569 patients with other GI disorders (e.g., ileus, GI tract bleeding, infectious colitis, ischemic colitis and colon adenoma) were ultimately included in the study. In cases of multiple admissions, the same patients were regarded as different individuals if the duration of admission exceeded 1 month. The actual number of patients enrolled in this study was 183 patients with IBD (68 with UC and 115 with CD; number of admissions, 1–11), 365 with GI cancer (number of admissions, 1–16) and 464 with other GI disorders (number of admissions, 1–5). Patient characteristics and laboratory data on admission among inpatients among IBD (Tables 1 and 2), GI cancer and other GI disorders (Table 2) enrolled in this study were sufficiently described in their clinical records. The study was approved by the Ethics Comittee of Asahikawa Medical Unversity (IRB No. 17092) and performed in accordance with the principles of the Declaration of Helsinki. The informed consent was waived.

The presence or absence of VTE was surveyed by CECT and/or US. In all cases scanned by CECT, the scanned area stretched from the chest to the pelvis, the level of which was the pulmonary artery to the proximal iliac vein. The scanned area was extended to the lower limbs and soles in suspicious cases that needed to be screened for VTE. In all cases scanned by US, the scanned area stretched from the superior vena cava to the venous in lower limbs. CECT scans from the chest to the lower limbs and soles were added mainly for the surveillance of VTE sites other than the lower limbs in all cases of VTE detected by US. VTE was diagnosed as positive if either CECT or US findings were positive for thrombus despite discrepancies in the presence or absence of thrombi between those 2 procedures. VTE was diagnosed when CECT showed defects in the venous or around the central venous catheter, regardless of the complaint of the patients. CECT or US was performed when VTE was suspected due to symptoms such as swelling, redness and pain of upper or lower limbs, respiratory discomfort, headache (indicated cerebral venous sinus thrombosis), and poor dropping of the CV catheter. Cases with VTE detected in above situations were defined as symptomatic VTE in this study. In addition, asymptomatic cases of VTE that were incidentally detected by CECT and/or US performed for the diagnosis and evaluation of a disease on and/or after admission was included in this study. The incidence rate and sites of VTE were investigated. The CT findings of cases who developed VTE at various sites are shown in Fig. 1. Patient characteristics and laboratory data of blood examinations in the 2 groups of IBD with and without VTE were compared to determine the risk factors for univariate and multivariate analyses. In addition, treatment against VTE, hemorrhagic complications associated with anticoagulant therapy, and mortality related to VTE were surveyed in IBD patients with VTE. Prophylaxis for VTE was performed as described in the manual for VTE developed at our hospital. Prophylaxis was carried out for patients with surgical treatment for IBD, cancer or other disorders using mechanical or pharmacological methods. However, in patients admitted to the department of internal medicine, no pharmacological prophylaxis was routinely performed because of the lack of adequate guidance in our country. However, mechanical prophylaxis was carried out for patients judged by their attending physicians as being adaptive. In patients with a history of VTE, the differential diagnosis between currently developing thrombus and previously developed thrombus was achieved based on the findings of CECT and US, which consisted of the CT value, presence or absence of organization, mural defects and bands of veins on CECT and the brightness, presence or absence of floating, shape and blood flow of veins on US. In patients receiving anticoagulant therapy, the decrease or disappearance of the VTE was confirmed after the therapy. In patients with a history of indwelling venous catheter, a thrombus sticking around the catheter was regarded as catheter-related “current” thrombus when CECT or US was performed with an indwelling venous catheter. In cases of VTE detected after the removal of the catheter, “current” thrombus at the site of the previously indwelling catheter was regarded as catheter-related thrombus.

Patient characteristics and laboratory data were collected in IBD with or without VTE from medical records. The characteristics were age, sex, BMI, disease duration, type of disease extent (UC: total colitis, left-sided, and proctitis type; CD: ileitis, ileo-colitis, and colitis type), disease activity on admission (UC: Clinical Activity Index; CD: CDAI), smoking, history of thrombosis, presence or absence of central venous alimentation, type of medical therapy treated in admission (prednisolone, immunomodulators, anti-tumor necrosis factor-α antibody, cytapheresis), presence or absence of abdominal surgery (within 2 weeks before or after surgery, consisting of total colectomy or partial resection of small intestine or colon), and systemic complications (diabetes mellitus, dyslipidemia, hypertension). Laboratory data on admission were the numbers of white blood cells and platelets, hemoglobin, serum levels of CRP, total protein, albumin, BUN, total cholesterol, triglyceride, hemoglobin A1c, ESR (1 hour), and, fibrinogen, D-dimer, fibrin degenerative product, anti-thrombin III, INR of PT, and active partial thromboplastin time.

In accordance with the guidelines for treating VTE, patients with VTE were referred to specialists and treated with anticoagulant, fibrinolytic therapy, indwelling of inferior vena cava (IVC) filter, catheter extraction, surgery, or no therapy against VTE, according to the condition of IBD or other digestive diseases. The period until the detection of VTE, treatment for VTE, and hemorrhagic complications were collected in VTE group in IBD inpatients. In addition, the in-hospital mortality associated with VTE was compared between the VTE and non-VTE groups.

Analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Australia). Fisher exact test and a chi-square test were applied to compare the incidence of VTE among groups. An unpaired t-test, Mann-Whitney U-test, and chi-square test were applied to compare patient characteristics and laboratory data between IBD patients with and without VTE. The cutoff values of the laboratory data with significant differences detected were determined by a receiver operating characteristics (ROC) analysis. A logistic regression analysis was applied to survey independent risk factors of IBD with VTE, which were detected by entering the significant factors revealed in the univariate analysis into a multivariate model. A P-value <0.05 was considered statistically significant.

VTE was observed in 7.1% (24/340) with IBD patients, which was significantly higher than the rates of 2.5% (14/557) with cancer of the GI tract and 0.88% (5/569) with other GI tract diseases (P<0.0001, respectively) (Fig. 2). IBD patients with VTE included 4 patients with deep venous thrombosis (DVT) of the lower limb and/or pulmonary thromboembolism, 2 with cerebral venous sinus thrombosis (CVT), 6 with PVT, and 12 with thrombosis related to a central venous catheter (Table 3). VTE with UC was observed in 16.9% (15/89), 3 of which had DVT of the lower limb and/or pulmonary thromboembolism, 2 CVT, 4 PVT, 6 thrombosis related to a central venous catheter. VTE with CD was observed in 3.6% (9/251), 1 of which had DVT of the lower limb and/or pulmonary thromboembolism, 2 PVT, and 6 thrombosis related to a central venous catheter (including 2 patients with home parental nutrition) (Table 3, Fig. 2). Among cases of VTE in GI cancer, VTE in cancer patients with distant metastasis or chemotherapy and in others (including those with early or operable advanced cancer) was observed at rates of 4.0% (12/303) and 0.79% (2/254), respectively. The site of VTE in patients with GI cancer was DVT of the lower limb and/or pulmonary thromboembolism in 8 and thrombosis related to a central venous catheter in 6; no patients developed VTE at the cerebral venous sinus or as PVT. UC patients had a significantly higher risk of VTE than CD patients (P<0.0001). The rate of VTE in UC patients was significantly higher than in those with cancer with distant metastasis or chemotherapy (4.0%) (P<0.0001), although the rate in CD patients was almost equivalent to that in those with cancer with distant metastasis or chemotherapy.

Six symptomatic and 18 asymptomatic cases of VTE were detected in IBD inpatients, 3 symptomatic and 11 asymptomatic cases were detected in patients with GI cancer, and 1 symptomatic and 4 asymptomatic cases were detected in patients with other GI diseases (Table 4). The sites of symptomatic and asymptomatic VTE are shown in Tables 5 and 6. Almost all VTE in lower limbs and/or pulmonary artery embolism were asymptomatic in both IBD and GI cancer patients. Both cases of CVT in IBD were symptomatic, while all 6 cases of PVT were asymptomatic.

The patient characteristics and laboratory data were compared between IBD patients with and without VTE. Seven risk factors of VTE with IBD were detected in a univariate analysis. The VTE group with IBD had a higher proportion of older patients (P=0.0180), especially those >50 years of age (P=0.0012), CV catheters (P<0.0001), prednisolone prescription (P<0.0001), and surgery (P<0.0001) (Table 5). On comparing the laboratory data between the 2 groups, the levels of serum albumin were significantly lower (P=0.0002) and those of CRP (P=0.0260) and D-dimer (P=0.0022) significantly higher in the IBD patients with VTE. The cutoff value was serum albumin ≤3.0 g/dL (P<0.0001), CRP >1.0 mg/dL (P=0.015), and D-dimer ≥1.5 ng/µL (P=0.0010) (Table 6), which were determined based on the threshold nearest to the top-left corner of the ROC curve (serum albumin: threshold, 3.10 g/dL; area under the curve [AUC], 0.6891; CRP: threshold, 1.12 mg/dL; AUC, 0.573; D-dimer: threshold, 1.61 ng/µL; AUC 0.66). In a multivariate analysis with a logistic regression analysis, only age >50 years (OR, 3.52; 95% CI, 1.25–9.94; P=0.018) and surgery (OR, 3.19; 95% CI, 1.02–9.98; P=0.046) were detected as independent risk factors (Table 7). Of 51 cases with IBD who underwent surgeries, 10 VTE cases included 9 elective and 1 emergency surgeries, and 41 non-VTE cases included 38 elective and 3 emergency surgeries. There was no marked difference in the rate of elective and emergent surgeries between IBD with and without VTE.

The average period until the detection of VTE (from admission) was 18.4 days. Treatment for VTE included anticoagulation therapy in 9 (unfractionated heparin, warfarin, direct oral anticoagulant), fibrinolytic and anticoagulant therapy in 2, IVC filter and anticoagulant therapy in 2, catheter extraction and anticoagulant therapy in 7, and no therapy (or observation) in 3. No hemorrhagic complications related to antithrombotic therapy occurred. The in-hospital mortality rate associated with VTE in all IBD inpatients was 0.29% (1/340). The rate in IBD patients with VTE was 4.2% (1/24), and only 1 CVT case resulted in death. In contrast, the rate in IBD patients without VTE was 0% (Table 8).