The postoperative bleeding rate and its risk factors in patients on antithrombotic therapy who undergo gastric endoscopic submucosal dissection

Abstract

Background: There is a lack of consensus regarding the risk of postoperative hemorrhage in patients on antithrombotic therapy who undergo endoscopic submucosal dissection (ESD).We examined postoperative bleeding rates and risk factors for postoperative hemorrhage from post-ESD gastric ulcers in patients on antithrombotic therapy.

Methods: The subjects of this study were 833 patients who underwent ESD of gastric tumors. Of these, 743 were not on antithrombotic therapy and 90 were on some form of antithrombotic therapy (46 on low-dose aspirin (LDA) only, 23 on LDA + thienopyridine, and 21 on LDA + warfarin). All patients commenced proton pump inhibitor (PPI) therapy immediately postoperatively. Antiplatelet agents were discontinued for 7 days preoperatively and postoperative Day 1, and anticoagulants for 5 days preoperatively and postoperative Day 1.

Results: The postoperative bleeding rate in the antithrombotic group was 23.3%, significantly higher than the 2.0% observed in the non-antithrombotic group. Significant differences were seen in patients in the antithrombotic group with and without postoperative bleeding according to ESD duration (p = 0.041), PPI + mucosal protective agent combination therapy (p = 0.039), and LDA + warfarin combination therapy (p < 0.001). Multivariate analysis of these factors yielded odds ratios of 1.04 for ESD duration, 14.83 for LDA + warfarin combination therapy, and 0.27 for PPI + mucosal protective agent combination therapy.

Conclusions: The risk of postoperative hemorrhage following gastric ESD was higher in patients with antithrombotic therapy than in those without that therapy. Among these patients, LDA + warfarin combination therapy and longer ESD duration were significant risk factors for postoperative bleeding. On the contrary, a mucosal protective agent to PPI therapy, lowering the odds ratio for postoperative bleeding, which suggests that the addition of a mucosal protective agent might be effective in preventing post-ESD hemorrhage in patients on antithrombotic therapy.

Figure 1

Endoscopic submucosal dissection protocol. For all patients, the day of the ESD procedure was set as Day 1. Patients were fasted until Day 2 and allowed to eat from Day 3. After resumption of oral feeding on Day 3, patients were commenced on an oral PPI. Patients regularly taking mucosal protective agents prior to undergoing ESD were asked to discontinue them on Days 1 and 2 and recommence them on Day 3. The protocol for antiplatelet agents was to discontinue them from Day −6 to Day 2, and that for anticoagulants was to discontinue them from Day −4 to Day 2. Heparin was substituted for anticoagulants while the latter were discontinued, maintaining the APTT at roughly twice the preheparinization level. Antiplatelet agents were recommenced as soon as possible on postoperative Day 3, following confirmation of hemostasis by EGD on Day 2. Anticoagulants were similarly recommenced on postoperative Day 3, and heparin was discontinued once the PT-INR had returned to a therapeutic level.

Figure 2

Study outline. There were 743 patients in the non-antithrombotic group and 90 in the antithrombotic group. The underlying disease in the antithrombotic group was a cardiac condition in 77.8% (70/90), and cerebrovascular disease in 22.2% (20/90). There were 46 patients on LDA monotherapy, 23 on LDA + thienopyridine and 21 on LDA + warfarin.