External validation and update of the International Medical Prevention Registry on Venous Thromboembolism bleeding risk score for predicting bleeding in acutely ill hospitalized medical patients: a retrospective single-center cohort study in Japan

The International Medical Prevention Registry for Venous Thromboembolism (IMPROVE) Bleeding Risk Score is the recommended risk assessment model (RAM) for predicting bleeding risk in acutely ill medical inpatients in Western countries. However, few studies have assessed its predictive performance in local Asian settings. We retrospectively identified acutely ill adolescents and adults (aged ≥ 15 years) who were admitted to our general internal medicine department between July 5, 2016 and July 5, 2021, and extracted data from their electronic medical records. The outcome of interest was the cumulative incidence of major and nonmajor but clinically relevant bleeding 14 days after admission. For the two-risk-group model, we estimated sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively). For the 11-risk-group model, we estimated C statistic, expected and observed event ratio (E/O), calibration-in-the-large (CITL), and calibration slope. In addition, we recalibrated the intercept using local data to update the RAM. Among the 3,876 included patients, 998 (26%) were aged ≥ 85 years, while 656 (17%) were hospitalized in the intensive care unit. The median length of hospital stay was 14 days. Clinically relevant bleeding occurred in 58 patients (1.5%), 49 (1.3%) of whom experienced major bleeding. Sensitivity, specificity, NPV, and PPV were 26.1% (95% confidence interval [CI]: 15.8–40.0%), 84.8% (83.6–85.9%), 98.7% (98.2–99.0%), and 2.5% (1.5–4.3%) for any bleeding and 30.9% (95% CI: 18.8–46.3%), 84.9% (83.7–86.0%), 99.0% (98.5–99.3%), and 2.5% (1.5–4.3%) for major bleeding, respectively. The C statistic, E/O, CITL, and calibration slope were 0.64 (95% CI: 0.58–0.71), 1.69 (1.45–2.05), − 0.55 (− 0.81 to − 0.29), and 0.58 (0.29–0.87) for any bleeding and 0.67 (95% CI: 0.60–0.74), 0.76 (0.61–0.87), 0.29 (0.00–0.58), and 0.42 (0.19–0.64) for major bleeding, respectively. Updating the model substantially corrected the poor calibration observed. In our Japanese cohort, the IMPROVE bleeding RAM retained the reported moderate discriminative performance. Model recalibration substantially improved the poor calibration obtained using the original RAM. Before its introduction into clinical practice, the updated RAM needs further validation studies and an optimized threshold.