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Introduction <p>Low-molecular-weight heparin (LMWH) is widely used for thromboprophylaxis and treatment in hospitalized patients; however, LMWH-related severe clinical bleeding (LSCB) remains a major concern. Existing risk scales have been developed for oral anticoagulants and have limited applicability to LMWH, leaving clinicians without reliable bedside tool.</p> Aim <p>This study aimed to evaluate the discriminatory performance of existing scales for predicting LSCB and develop a tailored nomogram for individualized risk prediction.</p> Method <p>Hospitalized medical patients prescribed LMWH between July 2021 and August 2024 at three tertiary hospitals in Hangzhou, China were retrospectively analyzed. Each LSCB case was matched with three non-LSCB controls from the same department and period. The prevalence of LSCBs, bleeding sites, and clinical characteristics are described. Receiver operating characteristic (ROC) curves were used to assess the predictive performance of existing scales. Variables with <i>p</i> &lt; 0.10 in univariate analysis were entered into logistic regression, a backward stepwise elimination (stay <i>p</i> &lt; 0.05) was applied to identify independent predictors and subsequently incorporated into a nomogram. Discrimination, calibration, and external validation were performed.</p> Results <p>Among 22,096 patients, 369 (1.67%) developed LSCB, most commonly severe gastrointestinal bleeding (74.3%), with a mean onset of 5.68&#xa0;days. A total of 1,089 patients with non-LSCB were matched as controls. Existing scales performed limited predictive value (AUC 0.52–0.68). Logistic regression identified 12 independent predictors: hypoproteinemia (albumin &lt; 30&#xa0;g/L), anemia (Hb &lt; 90&#xa0;g/L), active gastrointestinal ulcer, thrombocytopenia (platelets &lt; 75 × 10⁹/L), coagulation abnormalities (PT or aPTT &gt; 1.2 × ULN), cefoperazone/latamoxef exposure &gt; 7&#xa0;days, hypocalcemia ([Ca<sup>2</sup>⁺] &lt; 2.10&#xa0;mmol/L), aspirin therapy, dual antiplatelet therapy, renal dysfunction (GFR &lt; 60&#xa0;mL/min), hepatic impairment (AST or ALT ≥ 3 or TBIL ≥ 2 × ULN), and age &gt; 65&#xa0;years. Odds ratios ranged from 6.16 (hypoproteinemia) to 1.47 (age &gt; 65&#xa0;years). A nomogram, named LSCB-Score, incorporating these factors achieved AUC 0.890 in the derivation cohort. Calibration was good (Hosmer–Lemeshow <i>p</i> = 0.312), and predictions closely matched the observations. External validation yielded an AUC of 0.876, confirming robustness.</p> Conclusion <p>The existing scales for predicting LSCB lack accuracy in hospitalized patients. This newly developed nomogram (LSCB-Score) provides a practical framework for individualized bleeding risk assessment and facilitates safe management of LMWH in hospitals.</p>

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Beyond existing rating scales: development of a novel nomogram for predicting severe clinical bleeding associated with low-molecular-weight heparin in hospitalized medical patients

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  • 发表日期：

    2025年12月15日

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  • Zailin Fu,
  • Xia Zhan,
  • Min He,
  • Zhijun Dong,
  • Yuanyuan Fang,
  • Xiaoying Zhang,
  • Ting Zhou,
  • Bo Jin,
  • Dabu Zhu,
  • Jianrong Gu,
  • Yi Zhou,
  • Yifang Chen,
  • Minghua Xie,
  • Hong Yuan

摘要

Introduction

Low-molecular-weight heparin (LMWH) is widely used for thromboprophylaxis and treatment in hospitalized patients; however, LMWH-related severe clinical bleeding (LSCB) remains a major concern. Existing risk scales have been developed for oral anticoagulants and have limited applicability to LMWH, leaving clinicians without reliable bedside tool.

Aim

This study aimed to evaluate the discriminatory performance of existing scales for predicting LSCB and develop a tailored nomogram for individualized risk prediction.

Method

Hospitalized medical patients prescribed LMWH between July 2021 and August 2024 at three tertiary hospitals in Hangzhou, China were retrospectively analyzed. Each LSCB case was matched with three non-LSCB controls from the same department and period. The prevalence of LSCBs, bleeding sites, and clinical characteristics are described. Receiver operating characteristic (ROC) curves were used to assess the predictive performance of existing scales. Variables with p < 0.10 in univariate analysis were entered into logistic regression, a backward stepwise elimination (stay p < 0.05) was applied to identify independent predictors and subsequently incorporated into a nomogram. Discrimination, calibration, and external validation were performed.

Results

Among 22,096 patients, 369 (1.67%) developed LSCB, most commonly severe gastrointestinal bleeding (74.3%), with a mean onset of 5.68 days. A total of 1,089 patients with non-LSCB were matched as controls. Existing scales performed limited predictive value (AUC 0.52–0.68). Logistic regression identified 12 independent predictors: hypoproteinemia (albumin < 30 g/L), anemia (Hb < 90 g/L), active gastrointestinal ulcer, thrombocytopenia (platelets < 75 × 10⁹/L), coagulation abnormalities (PT or aPTT > 1.2 × ULN), cefoperazone/latamoxef exposure > 7 days, hypocalcemia ([Ca2⁺] < 2.10 mmol/L), aspirin therapy, dual antiplatelet therapy, renal dysfunction (GFR < 60 mL/min), hepatic impairment (AST or ALT ≥ 3 or TBIL ≥ 2 × ULN), and age > 65 years. Odds ratios ranged from 6.16 (hypoproteinemia) to 1.47 (age > 65 years). A nomogram, named LSCB-Score, incorporating these factors achieved AUC 0.890 in the derivation cohort. Calibration was good (Hosmer–Lemeshow p = 0.312), and predictions closely matched the observations. External validation yielded an AUC of 0.876, confirming robustness.

Conclusion

The existing scales for predicting LSCB lack accuracy in hospitalized patients. This newly developed nomogram (LSCB-Score) provides a practical framework for individualized bleeding risk assessment and facilitates safe management of LMWH in hospitals.