The risk of venous thromboembolism in patients with clinically overt gastrointestinal bleeding
Authors: Mohammed Almakadi, Christopher Sheasgreen, Ahmed Barefah, Lucy Lu, Nidhi Kumar Tyagi, Gillian Mazzetti, Lindsay Crabbe, Yuhong Yuan, Mark Crowther, Grigorios Leontiadis
Journal: American Journal of Hematology (2017)

The incidence of gastrointestinal bleeding (GIB) requiring hospitalization is estimated to be 120 per 100,000 persons per year.1 Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is one of the leading causes of morbidity and mortality in hospitalized patients.2 According to current guidelines, pharmacological prophylaxis for VTE is strongly recommended for all acutely ill hospitalized medical patients at increased risk of thrombosis.3 Patients with GIB might be at higher risk for VTE, as evidence for safety and efficacy of VTE prophylaxis in this population is lacking. We examined the frequency of VTE and use of pharmacological VTE prophylaxis in adult patients admitted between January 2007 and March 2011 for suspected or proven gastrointestinal bleeding to the four tertiary care hospitals in Hamilton, Ontario, Canada. Subsequent admissions for any patient already included in the study were censored. Patients with any prior history of active cancer (except non-melanoma skin cancer), myeloproliferative neoplasms, prior history of VTE, current flare of inflammatory bowel disease (IBD), or known hereditary or acquired thrombophilia were excluded. Patients were divided into two cohorts. The first included patients labelled as overt GIB if they had documented clinical evidence of GIB (hematemesis, melena, or hematochezia witnessed by a healthcare professional). The second included patients labelled as suspected GIB, who had presented with a history suspicious for GIB but did not meet criteria for overt GIB. VTE events were included if they occurred during index admissions and up to 6 weeks following discharge. Superficial venous thromboses, distal lower limb venous thromboses, or thromboses secondary to indwelling central venous catheters were not included. A total of 2142 admissions were identified (Supporting Information Figure 1). 63 admissions were excluded because the corresponding health records did not contain adequate information. After identifying 1491 potentially eligible patients, 357 were excluded: 42 had a prior history of VTE, 199 had active cancer, 16 patients had myeloproliferative neoplasms, 46 patients had thrombophilia, and 54 patients had an IBD flare. 693 patients were categorized as overt, and 441 patients were categorized as suspected. Baseline demographic data and treatments are summarized in (Table 1). Fisher's exact tests for categorical variables and Mann-Whitney U tests for continuous variables were performed. A cumulative VTE event-free curve of patients with overt GIB was generated (Supporting Information Figure 2). Statistical analysis was performed with IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. and StatsDirect Version 3.0.123. Cheshire, UK. Overt GIB (n = 693) Suspected GIB (n = 441) A minority of patients received early (within 24 h of hospitalization) pharmacological VTE prophylaxis (8%), with more patients in the suspected group [53 patients (12%)] compared with the overt group [47 patients (6.8%)] (Supporting Information Table 1). For patients who did not receive pharmacological VTE prophylaxis, VTE events occurred in 6 patients (0.93%) in the overt arm and 1 patient (0.3%) in the suspected arm. None of the patients who developed VTE in the overt arm had received pharmacological VTE prophylaxis, while one VTE event (1.9%) occurred in the suspected arm in a patient who had prophylaxis. After 40 days, 99.1% patients with overt GIB had had no VTE events (Supporting Information Figure 2). In one patient with overt GIB who experienced VTE, endoscopy revealed adenocarcinoma of the colon. In the overt arm, there were three proximal DVTs and three PEs, one of which was fatal. The two VTE events in the suspected arm were proximal DVTs, one occurred while the patient was on pharmacological VTE prophylaxis. Deaths occurred in 23 patients (3.3%) with overt GIB, and in 7 patients (1.6%) patients with suspected GIB. None of the deaths were attributed to anticoagulation. The causes of deaths are listed in (Supporting Information Table 2). We found that patients with suspected or overt GIB rarely received early VTE prophylaxis, but had very low rates of VTE. Patients with overt GIB had a slightly higher risk of developing VTE if they did not receive early prophylaxis compared to patients with suspected GIB who did not. Patients who received early prophylaxis were less likely to develop VTE compared to those who did not, and they did not require more blood product transfusions (Supporting Information Table 2). We believe that the lack of evidence for safety and efficacy of pharmacological prophylaxis in this patient population was the main reason for the low rate of pharmacological prophylaxis we observed. Current guidelines recommended against use of VTE prophylaxis in acutely ill hospitalized medical patients with low risk of thrombosis.3 Despite decreased use of VTE prophylaxis, we found the rate of VTE in the suspected GIB arm without prophylaxis to be 0.5%, which is close to the published VTE rate for hospitalized patients with low risk for developing VTE.4 However, the rate of VTE in the overt GIB group not receiving prophylaxis was numerically higher at 0.9%. In patients presenting with endoscopically confirmed GIB, others have previously shown no significant difference in VTE events between patients who received pharmacological prophylaxis and those who did not.5 However, their study included patients with known risks for VTE.5 We recognize the limitations of retrospective studies. Some patients at our tertiary centres could have been transferred back to local hospitals resulting in missed VTE or bleeding events. We were also not able to account for non-pharmacological VTE prophylaxis, though pneumatic compression devices were not in common use outside of the ICU at our institutions during the study period. However, our study is one of the largest retrospective reviews of its kind. We had a rigorous process for chart extraction and data analysis. Finally, we endeavored to capture every potentially eligible event across four acute care hospitals to increase generalizability. For instance, we chose not to use endoscopy as a criterion to confirm GIB to improve the applicability of our findings as not all hospitals can provide early endoscopic assessment for every patient presenting with potential GIB. This study suggests that patients with proven or suspected GIB rarely receive early VTE prophylaxis, but remain at low risk of VTE, and the use of pharmacological prophylaxis was not associated with worse GIB outcomes. Additional Supporting Information may be found online in the supporting information tab for this article. Supporting Information Figures Supporting Information Figure 1 Supporting Information Figure 2 Supporting Information Table 1 Supporting Information Table 2 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.