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CC BY 4.0 · Thromb Haemost
DOI: 10.1055/a-2642-0241
Stroke, Systemic or Venous Thromboembolism

Performance of Bleeding Risk Scores for Major Bleeding in Anticoagulated Patients with Pulmonary Embolism: Insights from the CURES Registry-2

Authors

  • Yuzhi Tao

    1   Department of Pulmonary and Critical Care Medicine, The First Bethune Hospital of Jilin University, Jilin University, Changchun, China
    2   National Centre for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Centre for Respiratory Diseases, Beijing, China
    3   Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
    4   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China

  • Hong Chen

    5   Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

  • Chunling Dong

    6   Department of Pulmonary and Critical Care Medicine, The Second Hospital, Jilin University, Changchun, China

  • Jie Zhang

    6   Department of Pulmonary and Critical Care Medicine, The Second Hospital, Jilin University, Changchun, China

  • Yiwei Shi

    7   Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, China

  • Xiaomao Xu

    8   Department of Pulmonary and Critical Care Medicine, Beijing Hospital, Beijing, China

  • Maoyun Wang

    9   Department of Pulmonary and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China

  • Ling Zhu

    10   Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China

  • Juhong Shi

    11   Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China

  • Yingqun Ji

    12   Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Shanghai, China

  • Hong Chen

    13   Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, China

  • Zhe Cheng

    14   Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

  • Yongjun Tang

    15   Department of Pulmonary and Critical Care Medicine, Xiangya Hospital Central South University, Changsha, China

  • Yanxia Li

    16   Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China

  • Chaosheng Deng

    17   Department of Pulmonary and Critical Care Medicine, The first affiliated Hospital of Fujian Medical University, Fuzhou, China

  • Qin Luo

    18   Department of Pulmonary and Critical Care Medicine, The Third Clinical Medical College of Xinjiang Medical University, Urumqi, China

  • Pinyao Lu

    19   Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Chengde Medical university, Chengde, China

  • Yuanhua Yang

    20   Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

  • Linfeng Xi

    2   National Centre for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Centre for Respiratory Diseases, Beijing, China
    3   Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
    4   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China
    21   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Capital Medical University, Beijing, China

  • Yu Zhang

    2   National Centre for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Centre for Respiratory Diseases, Beijing, China
    3   Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
    4   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China

  • Rui Liang

    22   Beijing University of Chinese Medicine China-Japan Friendship School of Clinical Medicine, Beijing, China

  • Dingyi Wang

    2   National Centre for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Centre for Respiratory Diseases, Beijing, China
    3   Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
    4   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China

  • Guohui Fan

    2   National Centre for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Centre for Respiratory Diseases, Beijing, China
    3   Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
    4   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China

  • Wanmu Xie

    2   National Centre for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Centre for Respiratory Diseases, Beijing, China
    3   Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
    4   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China

  • Jun Wan

    23   Department of Pulmonary and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

  • Zhu Zhang

    2   National Centre for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Centre for Respiratory Diseases, Beijing, China
    3   Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
    4   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China

  • Shuai Zhang

    2   National Centre for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Centre for Respiratory Diseases, Beijing, China
    3   Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
    4   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China

  • Yunxia Zhang

    2   National Centre for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Centre for Respiratory Diseases, Beijing, China
    3   Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
    4   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China

  • Qiang Huang

    2   National Centre for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Centre for Respiratory Diseases, Beijing, China
    3   Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
    4   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China

  • Qian Gao

    2   National Centre for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Centre for Respiratory Diseases, Beijing, China
    3   Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
    4   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China

  • Min Liu

    24   Department of Radiology, China-Japan Friendship Hospital, Beijing, China

  • Peiran Yang

    25   Department of Physiology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China

  • Shengfeng Wang

    26   Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
    27   Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China

  • Chen Wang

    1   Department of Pulmonary and Critical Care Medicine, The First Bethune Hospital of Jilin University, Jilin University, Changchun, China
    2   National Centre for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Centre for Respiratory Diseases, Beijing, China
    3   Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
    4   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China

  • Zhenguo Zhai

    2   National Centre for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Centre for Respiratory Diseases, Beijing, China
    3   Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
    4   Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China
    • on behalf of the CURES investigators

Funding The Fund of the National Key Research and Development Program of China (grant number 2023YFC2507200); the CAMS Innovation Fund for Medical Sciences (CIFMS) (grant numbers 2021-I2M-1-061, 2021-I2M-1-049); the National High Level Hospital Clinical Research Funding (grant number 2022-NHLHCRF-LX-01); and the National Natural Science Foundation of China (No. 82241029).
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Graphical Abstract

Abstract

Background

Most bleeding risk scores for pulmonary embolism (PE) were developed in patients receiving traditional anticoagulants. Evidence in East Asian populations and its applicability to direct oral anticoagulants (DOACs) remain limited.

Methods

This post-hoc analysis was based on a multicentre, prospective study (NCT02943343) conducted from 2016 to 2021. The predictive performance of bleeding risk scores was assessed using a time-dependent area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and decision curve analysis (DCA). Propensity score matching (PSM) was adjusted for baseline characteristics. We analyzed the impact of initial DOAC versus low-molecular-weight heparin (LMWH) on outcomes. The endpoint was major bleeding (MB) within 90 days and composite outcomes (all-cause mortality, recurrent VTE, and MB).

Results

Of 7,619 patients with PE, 1.4% (107 patients) experienced MB within 90 days. The RIETE score showed a modest predictive ability (AUC: 0.70; 95% CI, 0.65–0.75) for predicting 90-day MB and demonstrated a predictive advantage in the DCA results. NRI also revealed significantly better reclassification capability than the other scores, except for HAS-BLED. Among low-risk patients classified by the RIETE score, initial DOAC treatment significantly reduced 14-day composite outcomes compared with LMWH (HR = 0.13; 95% CI, 0.02–0.93). Furthermore, DOACs at discharge did not increase the risk of MB or composite outcomes.

Conclusion

RIETE score shows modest performance in predicting MB and identifying low bleeding risk in PE patients, which could potentially guide early DOAC use. Further studies are needed to test its clinical utility, especially in East Asian populations.

Keywords

pulmonary embolism - anticoagulation - major bleeding - score - prediction

Data Availability Statement

The data underlying this article cannot be shared publicly due to ethical reasons. The data will be shared on reasonable request to the corresponding author.


Authors' Contribution

Concept and design: Y.T., H.C., C.D., J.Z., Y.S., X.X., C.W., and Z.Z.; acquisition, analysis, or interpretation of data: all authors; drafting of the manuscript: Y.T., H.C., C.D., M.W., L.Z., L.X., Y.Z., C.W., and Z.Z.; critical review of the manuscript for important intellectual content: all authors; statistical analysis: Y.T., J.S., Y.J., H.C., Z.C., Y.T., L.R., D.W., G.F., and S.W.; obtained funding: C.W. and Z.Z.; administrative, technical, or material support: Y.L., C.D., Q.L., P.L., Y.Y., C.W., and Z.Z.; supervision: J.W., W.X., C.W., and Z.Z. Y.T. and Z.Z. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.


* The members of the CURES are listed in the [Supplementary Appendix] (available in the online version).


Supplementary Material



Publication History

Received: 25 December 2024

Accepted: 21 June 2025

Accepted Manuscript online:
24 June 2025

Article published online:
17 July 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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