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World J Gastroenterol. May 21, 2023; 29(19): 2916-2931
Published online May 21, 2023. doi: 10.3748/wjg.v29.i19.2916
Assessment of delayed bleeding after endoscopic submucosal dissection of early-stage gastrointestinal tumors in patients receiving direct oral anticoagulants
Mitsushige Sugimoto, Masaki Murata, Takashi Kawai
Mitsushige Sugimoto, Takashi Kawai, Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo 160-0023, Japan
Masaki Murata, Department of Gastroenterology, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
Author contributions: Sugimoto M wrote the paper; Sugimoto M, Murata M and Kawai T collected the data.
Supported by the Grant-in-Aid for Scientific Research in Japan, No. 21K07949.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mitsushige Sugimoto, AGAF, MD, PhD, Professor, Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. sugimo@tokyo-med.ac.jp
Received: January 24, 2023
Peer-review started: January 24, 2023
First decision: March 21, 2023
Revised: April 3, 2023
Accepted: April 24, 2023
Article in press: April 24, 2023
Published online: May 21, 2023
Abstract

Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection (ESD) for early-stage gastrointestinal tumors. The rate of post-ESD bleeding for gastric cancer is higher (around 5%-8%) than that for esophagus, duodenum and colon cancer (around 2%-4%). Although investigations into the risk factors for post-ESD bleeding have identified several procedure-, lesion-, physician- and patient-related factors, use of antithrombotic drugs, especially anticoagulants [direct oral anticoagulants (DOACs) and warfarin], is thought to be the biggest risk factor for post-ESD bleeding. In fact, the post-ESD bleeding rate in patients receiving DOACs is 8.7%-20.8%, which is higher than that in patients not receiving anticoagulants. However, because clinical guidelines for management of ESD in patients receiving DOACs differ among countries, it is necessary for endoscopists to identify ways to prevent post-ESD delayed bleeding in clinical practice. Given that the pharmacokinetics (e.g., plasma DOAC level at both trough and Tmax) and pharmacodynamics (e.g., anti-factor Xa activity) of DOACs are related to risk of major bleeding, plasma DOAC level and anti-FXa activity may be useful parameters for monitoring the anti-coagulate effect and identifying DOAC patients at higher risk of post-ESD bleeding.

Keywords: Direct oral anticoagulants, Gastrointestinal tumors, Endoscopic submucosal dissection, Delayed bleeding, Adverse events, Anticoagulants

Core Tip: Recent international clinical guidelines for early-stage gastrointestinal tumors recommend endoscopic submucosal dissection (ESD) as the first-line treatment. Direct oral anticoagulants (DOACs) are a major risk factor for post-ESD bleeding and the pharmacokinetics and pharmacodynamics of DOACs may be related to risk of post-ESD bleeding. Therefore, one way to monitor the anticoagulant effect of DOACs in clinical practice may be to develop a system that effectively measures anti–FXa activity and plasma concentration. In the future, it may be useful to stratify risk of post-ESD delayed bleeding based on a scoring system that includes pharmacological parameters of DOACs.