Pharmacodynamics of direct oral anticoagulants associated with post-endoscopic delayed mucosal resection bleeding of colorectal neoplasms
Anticoagulant effects of direct oral anticoagulants (DOACs) are influenced by their plasma levels and anti-factor Xa (FXa) activity. Delayed bleeding is a major adverse event associated with endoscopic mucosal resection (EMR) of colorectal neoplasms. However, the association between post-EMR bleeding and pharmacodynamics in patients taking DOAC remains unknown. This study investigated the association between pharmacological risk factors and delayed bleeding in patients receiving DOAC. This multicenter prospective trial in Japan evaluated the incidence of post-EMR delayed bleeding in DOAC users between April 2018 and May 2022 and determined the association of post-EMR delayed bleeding with plasma levels and FXa activity. The incidence of post-EMR delayed bleeding was 10.5% (95% confidence interval [CI]: 5.3%-18.0%). There were large individual differences in plasma levels and FXa activity for each DOAC. At the trough and Tmax, plasma DOAC levels and plasma level/dose ratios were significantly correlated with FXa activity. Multivariate analysis showed that high anticoagulant ability was a risk factor for post-EMR delayed bleeding (adjusted OR, 12.211; 95% CI: 1.081-137.922, p = 0.043). DOAC users with high anticoagulant activity may be at higher risk of post-EMR delayed bleeding from colorectal neoplasms.
Authors
- Tatsuya Mikami (ORCID: https://orcid.org/0000-0002-6657-6446)
- Manabu Sawaya
- Toshiya Katsura (ORCID: https://orcid.org/0000-0002-7789-8803)
- Tomohiro Terai
- Daiki Hira
- Satoshi Ueshima (ORCID: https://orcid.org/0000-0002-8828-1083)
- Yohei Furumoto (ORCID: https://orcid.org/0000-0002-3213-6936)
- Shigetsugu Tsuji (ORCID: https://orcid.org/0000-0002-3948-2313)
- Yasuhiko Maruyama (ORCID: https://orcid.org/0000-0003-0269-7799)
- Masaki Murata (ORCID: https://orcid.org/0000-0002-4951-0584)
- Yasuaki Nagami (ORCID: https://orcid.org/0000-0002-4617-2188)
- Yashiro Yoshizawa
- Masaki Ominami
- Takashi Kawai (ORCID: https://orcid.org/0000-0002-3557-7649)
- Shunichiro Orihara (ORCID: https://orcid.org/0000-0003-0168-1250)
- Sayana Matsuda
- Tomohiro Terada (ORCID: https://orcid.org/0000-0002-4559-9753)
- Nobuaki Yagi
- Fujishiro Mitsuhiro
- Takeshi Yamamura
- Mitsushige SUGIMOTO
- Naohisa Yoshida
- Satoshi Osawa
- Shin’ichi Miyamoto
- Yoji Takeuchi
- Ken Inoue
- Takanori Yamada
Institutions
- Ritsumeikan University (JP)
- Asahi University (JP)
- Hirosaki University (JP)
- Tokyo Medical University (JP)
- Oita University (JP)
- Kyoto Medical Center (JP)
- Hamamatsu University School of Medicine (JP)
- Kyoto Prefectural University of Medicine (JP)
- Iwata City Hospital (JP)
- Tokyo Metropolitan Bokutoh Hospital (JP)
- Tokyo Medical University Hospital (JP)
- Ishikawa Prefectural Central Hospital (JP)
- Seirei Hamamatsu General Hospital (JP)
- Fujieda Municipal General Hospital (JP)
- Kyoto University Hospital (JP)
- Osaka International Cancer Institute (JP)
- Hirosaki University Hospital (JP)
- Osaka Metropolitan University (JP)
- Nagoya University (JP)
- Tokyo Metropolitan University (JP)
- The University of Tokyo (JP)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-12-22
- DOI
- https://doi.org/10.1038/s41598-025-33056-w
- Primary Topic
- Gastrointestinal Bleeding Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00