Evaluation of the bleeding risk with various antithrombotic therapies after gastric endoscopic submucosal dissection

Abstract

Background and study aims Patients receiving antithrombotic drugs have a higher risk of postoperative bleeding and thromboembolic events related to endoscopic procedures. The aim of this study was to evaluate the relationship between various antithrombotic therapies and bleeding after gastric endoscopic submucosal dissection (ESD) (post-ESD bleeding). Patients and methods Among 529 consecutive gastric ESD procedures (483 patients with 579 legions), 100 patients with 121 lesions who underwent 108 procedures were on antithrombotic therapy (group A) and 382 patients with 458 lesions who underwent 421 procedures were not on antithrombotic therapy (group B). The ratio of post-ESD bleeding between the two groups and the bleeding risk related to various antithrombotic therapies were investigated. Results Postoperative bleeding was more frequent in group A (11.1 %) than in group B (3.3 %). No thromboembolic events were reported in either group. Further investigation of antithrombotic therapies in group A demonstrated that various combinations of antithrombotic agents and heparin replacement were associated with a higher ratio of post-ESD bleeding. Multivariate analyses revealed that dual antiplatelet therapy (odds ratio [OR] 10.9, 95 % confidence interval [CI] 2.1 – 49.5; P = 0.005) and heparin replacement (OR 34.4, 95 %CI 9.4 – 133.2; P < 0.001) were associated with the increased risk of post-ESD bleeding. In patients on antiplatelet therapy, post-ESD bleeding tended to occur in the early postoperative period compared with patients on anticoagulant therapy. Conclusions It is necessary to be cautious regarding post-ESD bleeding in patients requiring antithrombotic therapy, especially patients receiving dual antiplatelet therapy and heparin replacement. A further prospective study with a large sample will be needed to confirm these findings.

Management of adverse events related to endoscopic resection of upper gastrointestinal neoplasms: Review of the literature and recommendations from experts

“…Recently published supplementary issue of JGES guidelines for management of patients taking anticoagulants suggests the possibility of continuation of warfarin instead of heparin bridging therapy during high‐bleeding‐risk endoscopic procedures because many studies showed a high incidence of delayed bleeding after gastric ESD in patients received heparin bridging therapy (10.8–61.5%; Table ) …”

“…77,78 In terms of multiple antithrombotic therapies, the JGES guidelines recommend that thienopyridine should be withdrawn or replaced by aspirin or cilostazol monotherapy for high-risk bleeding procedure. 70 Because of the high delayed bleeding rates after gastric ESD in patients taking multiple antithrombotics including anticoagulants, ranging from 11.1% to 45.4% (Table 5), 75,76,[79][80][81][82][83][84][85] use of multiple antithrombotic drugs is one of the high risk factors. A meta-analysis indicated that the risk of delayed bleeding after gastric ESD in regular users of multiple antithrombotic drugs was significantly higher than never users (odds ratio 5.17 [95% CI: 3.13-8.54]).…”

“…77 Recently published supplementary issue of JGES guidelines for management of patients taking anticoagulants suggests the possibility of continuation of warfarin instead of heparin bridging therapy during high-bleeding-risk endoscopic procedures 86 because many studies showed a high incidence of delayed bleeding after gastric ESD in patients received heparin bridging therapy (10.8-61.5%; Table 6). 76,79,[82][83][84][85]87,88 Systematic literature search formula for English publication: [endoscopic submucosal dissection] AND [bleeding] 73 21 2 (9.5) 21 5 (23.8) Sanomura (2014) 74 28 1 (3.6) 66 3 (4.5) Tounou (2015) 75 14 2 (14.3) --Igarashi (2017) 76 33 4 (12.1) 171 19 (11.1) Dong (2017) 77 Continued use of LDA does not increase the risk of bleeding after gastric ESD compared with interrupted use of LDA (meta-analysis) ESD, endoscopic submucosal dissection; LDA, low-dose aspirin.…”

Bleeding after endoscopic submucosal dissection of gastric lesions

“…The 2012 guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment in Japan recommended replacing warfarin with heparin for those at a high risk of bleeding . However, subsequent studies indicated that patients on heparin replacement therapy had a higher incidence of delayed hemorrhage than those continuing warfarin . When analyzing the risks of hemorrhage during heparin replacement therapy, Dong et al performed a meta‐analysis that included 10 540 patients from 16 studies, showing that heparin replacement therapy could increase the incidence of post‐ESD bleeding.…”

“…If their INR levels remain elevated, a small amount of vitamin K should be given a day before the operation while paying attention to the possibility of an embolism. If the patient is at a high risk of thrombosis, warfarin should be sustained when INR is within the scope of treatment, or can be temporarily replaced with DOAC . The Japanese guidelines 2017 also recommend patients to stop taking DOAC if they are at a low risk of thrombosis; while those at a high risk of thrombosis should continue to take DOAC until the day before operation and interupt DOAC on the morning of the operation.…”