Pharmacodynamics of direct oral anticoagulants associated with post-endoscopic delayed mucosal resection bleeding of colorectal neoplasms

Masaki Murata; Mitsushige SUGIMOTO; Satoshi Ueshima; Yasuaki Nagami; Masaki Ominami; Yohei Furumoto; Tatsuya Mikami; Manabu Sawaya; Naohisa Yoshida; Ken Inoue; Yasuhiko Maruyama; Tomohiro Terai; Shigetsugu Tsuji; Takeshi Yamamura; Takanori Yamada; Yoji Takeuchi; Nobuaki Yagi; Satoshi Osawa; Yashiro Yoshizawa; Shunichiro Orihara; Shin’ichi Miyamoto; Sayana Matsuda; Daiki Hira; Tomohiro Terada; Toshiya Katsura; Fujishiro Mitsuhiro; Takashi Kawai

doi:10.1038/s41598-025-33056-w

Key result

DOACs are linked to a ~11% bleeding rate after endoscopic mucosal resection amid variable FXa activity.

Figures

Why the study?

The association between post-EMR delayed bleeding and DOAC pharmacodynamics, including plasma levels and anti-factor Xa activity, remains unknown.

Does high anticoagulant ability in DOAC users increase the risk of post-EMR delayed bleeding in patients with colorectal neoplasms?

Key Points

To investigate the association between pharmacological risk factors—specifically plasma drug concentrations and anti-factor Xa activity—and post-endoscopic mucosal resection delayed bleeding in patients taking direct oral anticoagulants.
Multicenter prospective trial conducted in Japan between April 2018 and May 2022 among direct oral anticoagulant (DOAC) users undergoing endoscopic mucosal resection (EMR) for colorectal neoplasms.
Evaluated plasma DOAC concentrations, plasma level-to-dose ratios, and anti-factor Xa (FXa) activity at trough and maximum plasma concentration (Tmax) to measure associations with delayed bleeding.
The incidence of post-EMR delayed bleeding was 10.5% (95% CI: 5.3%-18.0%).
Plasma DOAC levels and plasma level/dose ratios correlated significantly with FXa activity at both trough and Tmax, though large individual variations were observed across patients.
Multivariate analysis showed that high anticoagulant ability was a significant independent risk factor for post-EMR delayed bleeding (adjusted OR, 12.211; 95% CI: 1.081-137.922, p = 0.043).

Structured PICO

Does high anticoagulant ability in DOAC users increase the risk of post-EMR delayed bleeding in patients with colorectal neoplasms?

P

Population

105 DOAC users (apixaban, edoxaban, or rivaroxaban) aged ≥ 20 years undergoing hot endoscopic mucosal resection (EMR) for colorectal neoplasms across 14 institutions in Japan.

I

Intervention

Direct oral anticoagulants (apixaban, edoxaban, or rivaroxaban) with high anticoagulant ability (assessed via plasma levels and FXa activity at trough and Tmax)

C

Comparator

DOAC users with lower anticoagulant ability

O

Outcome

Post-EMR delayed bleeding (defined as bleeding with clinical signs such as bloody stool or a decrease in hemoglobin > 2 g/dL confirmed via emergency endoscopy within 28 days post-EMR)safety

DOAC users with high anticoagulant activity, as measured by FXa activity and plasma levels, are at a significantly higher risk of delayed bleeding following endoscopic mucosal resection of colorectal neoplasms.

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Implication

High FXa activity may increase post-EMR bleeding risk in DOAC users; leaves open need for prospective periprocedural studies.

Abstract

UNLABELLED: 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 T SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-33056-w.

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Cite This Study

Murata et al. (2025) studied this question. Post-endoscopic mucosal resection bleeding occurred in 10.5% of patients using direct oral anticoagulants, with significant variability in plasma levels and FXa activity.

synapsesocial.com/papers/6963223291e05aa366cb8c79 https://doi.org/10.1038/s41598-025-33056-w

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Pharmacodynamics of direct oral anticoagulants associated with post-endoscopic delayed mucosal resection bleeding of colorectal neoplasms

Figures

Key Points

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Pharmacodynamics of direct oral anticoagulants associated with post-endoscopic delayed mucosal resection bleeding of colorectal neoplasms

Figures

Key Points

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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