Predictive accuracy of diagnostic tests for excessive bleeding in cardiac surgery: the COPTIC-C study

Purpose We tested the hypothesis that addition of biomarkers of multimorbidity and biological ageing would improve the predictive accuracy of point-of-care viscoelastometry or laboratory tests of coagulation for clinically important bleeding following cardiac surgery. Methods The analyses included 2437 participants in the Coagulation and Platelet laboratory Testing in Cardiac surgery (COPTIC study) with complete clinical, TEG®5000 Thromboelastography, ROTEM®, Multiplate® aggregometry, full blood count, laboratory reference tests of coagulopathy, and biomarkers of biological ageing and multimorbidity. Models with different biomarkers to predict the composite primary outcome, Clinically Important Bleeding, was developed using logistic regression and internally validated using 10-fold cross-validation. Discrimination, calibration, and clinical utility of the models were assessed comprehensively. Results For the primary outcome, the AUROC for the best predictive model using TEG/ROTEM with other biomarkers was 0.694 (0.612–0.775). The best predictive model included laboratory reference tests of coagulation, full blood count results, and biomarkers of multimorbidity and ageing, AUROC=0.701 (0.620–0.781), although clinical utility was not superior to using laboratory reference tests alone. Discrimination was higher for components of the primary outcome; large volume (≥4 units) red cell transfusion 0.754 (0.602–0.903), and large volume procoagulant transfusion 0.723 (0.590–0.857), but not for excess loss in drains/re-sternotomy 0.701 (0.613–0.788). Calibration was generally good among the models. Conclusion Diagnostic tests for bleeding following cardiac surgery demonstrate moderate discrimination, although this was influenced by the definition of bleeding. Small improvements in discrimination with inclusion of additional disease biomarkers, with similar calibration and clinical utility. Take-home message 1. Current diagnostic tests demonstrate moderate predictive accuracy for excessive bleeding following cardiac surgery. In this study, addition of biomarkers of multimorbidity and biological ageing improved discrimination but not clinical utility. 2. Existing clinical definitions of bleeding represent heterogeneous phenotypes, presenting a barrier to research investigating the disease processes. Important abbreviations used in this paper: CIB – Clinically Important Bleeding CCB – Clinical Concern about Bleeding AUROC – Area Under the Receiver Operating Characteristic Curve