External Validation of the IMPROVE Risk Score for Predicting Bleeding in Hospitalized COVID-19 Patients

Yuzhi Tao; Feiya Xu; Jing Han; Chaosheng Deng; Rui Liang; Lijun Chen; Binliang Wang; Yunhui Zhang; Weijia Liu; Dingyi Wang; Guohui Fan; Zhaofei Chen; Yinong Chen; Kaiyuan Zhen; Yunxia Zhang; Shuai Zhang; Qiang Huang; Jun Wan; Wanmu Xie; Peiran Yang; Zhu Zhang; Chen Wang; Zhenguo Zhai

doi:10.1007/s11606-025-09431-8

External Validation of the IMPROVE Risk Score for Predicting Bleeding in Hospitalized COVID-19 Patients

J Gen Intern Med. 2025 Feb 20. doi: 10.1007/s11606-025-09431-8. Online ahead of print.

Authors

Yuzhi Tao^{1

2}, Feiya Xu³, Jing Han⁴, Chaosheng Deng⁵, Rui Liang⁶, Lijun Chen⁷, Binliang Wang⁸, Yunhui Zhang⁹, Weijia Liu⁴, Dingyi Wang², Guohui Fan², Zhaofei Chen^{2

10}, Yinong Chen^{2

10}, Kaiyuan Zhen^{2

10}, Yunxia Zhang², Shuai Zhang², Qiang Huang², Jun Wan¹¹, Wanmu Xie², Peiran Yang¹², Zhu Zhang¹³, Chen Wang^{14

15}, Zhenguo Zhai¹⁶

Affiliations

¹ The First Bethune Hospital of Jilin University, Jilin University, Changchun, China.
² National Center for Respiratory Medicinestate Key Laboratory of Respiratory Health and Multimorbiditynational Clinical Research Center for Respiratory Diseasesinstitute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
³ China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
⁴ Department of Pulmonary and Critical Care Medicine, Guizhou Provincial People's Hospital, Guiyang, China.
⁵ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
⁶ Beijing University of Chinese Medicine China-Japan Friendship School of Clinical Medicine, Beijing, China.
⁷ Department of Pulmonary and Critical Care Medicine, The First People's Hospital of Yinchuan, Yinchuan, China.
⁸ Department of Pulmonary and Critical Care Medicine, Taizhou First People's Hospital, Taizhou, China.
⁹ Department of Pulmonary and Critical Care Medicine, First People's Hospital of Yunnan Province, Yunnan, China.
¹⁰ Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China.
¹¹ Department of Pulmonary and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
¹² Department of Physiology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, School of Basic Medicine Peking, Chinese Academy of Medical Sciences, Union Medical College, Beijing, 100005, China.
¹³ National Center for Respiratory Medicinestate Key Laboratory of Respiratory Health and Multimorbiditynational Clinical Research Center for Respiratory Diseasesinstitute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China. zhuperfectlife@126.com.
¹⁴ The First Bethune Hospital of Jilin University, Jilin University, Changchun, China. cyh-birm@263.net.
¹⁵ National Center for Respiratory Medicinestate Key Laboratory of Respiratory Health and Multimorbiditynational Clinical Research Center for Respiratory Diseasesinstitute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China. cyh-birm@263.net.
¹⁶ National Center for Respiratory Medicinestate Key Laboratory of Respiratory Health and Multimorbiditynational Clinical Research Center for Respiratory Diseasesinstitute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China. zhaizhenguo2011@126.com.

PMID: 39979703
DOI: 10.1007/s11606-025-09431-8

Abstract

Background: COVID-19 patients are at increased risk of thrombosis and bleeding, but no standardized bleeding risk assessment tool has been recommended.

Objective: This study evaluates the predictive value of the IMPROVE Bleeding Risk Score (BRS) in hospitalized COVID-19 patients.

Design: A multicenter, prospective cohort of 3,886 hospitalized COVID-19 patients across six tertiary hospitals in China between December 1, 2022, and January 31, 2023.

Participants: Patients were objectively diagnosed with COVID-19 by pathogen or antibody detection and followed for 90 days.

Main measures: The primary outcomes were major bleeding (MB) and clinically relevant non-major bleeding (CRNMB). We evaluated the IMPROVE BRS predictive performance using hazard ratios (HRs), positive and negative predictive values, the area under the receiver operating characteristic curve (AUC), and calibration.

Key results: Among 3,886 hospitalized COVID-19 patients (median age 74, IQR 62-84), 42 MB (1.1%) and 47 CRNMB (1.2%) events occurred within 90 days. The IMPROVE BRS performed well in predicting MB events, with an AUC of 0.84 (95% CI, 0.77-0.91) at 90 days. Calibration plots indicated good calibration. High-risk patients had a significantly higher bleeding risk than low-risk patients, even after adjusting for low molecular weight heparin (LMWH) thromboprophylaxis (MB: adjusted HR 6.63, 95% CI 3.62-12.15; CRNMB: adjusted HR 3.69, 95% CI 2.04-6.71). Subgroup analysis indicated that LMWH thromboprophylaxis significantly increased MB risk in elderly patients with high bleeding risk (14 days: adjusted HR 5.45, 95% CI 1.15-25.94; 30 days: adjusted HR 4.16, 95% CI 1.11-15.53).

Conclusions: The IMPROVE BRS effectively predicted MB risk in COVID-19 patients and provided valuable guidance for LMWH thromboprophylaxis in elderly patients. Further research is needed to validate its applicability in different populations and refine threshold values for improved predictive accuracy.

Keywords: COVID-19; bleeding Risk; clinical Prediction Model; external Validation.

Abstract

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