ACT and APTT Variability as Prognostic Markers for 28-Day In-Hospital Mortality in ECMO Patients: Development and External Validation of a Nomogram

Venovenous and venoarterial extracorporeal membrane oxygenation (ECMO) provides life support for patients with refractory cardiopulmonary failure, but bleeding and thrombotic complications remain major causes of mortality. Conventional monitoring based on single activated clotting time (ACT) and activated partial thromboplastin time (APTT) measurements may not adequately capture intra-individual coagulation fluctuations. Previous longitudinal work linked APTT variability with bleeding and mortality, but ACT variability has rarely been evaluated concurrently. This dual-cohort retrospective study evaluated the prognostic value of ACT and APTT variability for 28-day in-hospital mortality and developed an externally validated nomogram. The derivation cohort included 300 patients from the MIMIC-IV database, and the external validation cohort included 200 patients from our ICU. Intra-individual coefficients of variation (CVs) of serial ACT and APTT measurements during ECMO support were calculated. Candidate predictors were screened using LASSO Cox regression and evaluated by Cox proportional hazards regression. Kaplan–Meier analysis compared survival across ACT-CV and APTT-CV tertiles, and model performance was assessed by discrimination, calibration, and decision curve analysis. LASSO identified age, ACT-CV, APTT-CV, lactate, and SOFA score as candidate predictors. Multivariate Cox regression showed that elevated ACT-CV (HR=2.875, 95% CI 1.692–4.891, P<0.001) and APTT-CV (HR=2.630, 95% CI 1.547–4.471, P<0.001) were independent predictors of 28-day mortality. Mortality risk increased progressively across higher ACT-CV and APTT-CV tertiles, with significantly poorer survival in patients with greater coagulation variability (all log-rank P<0.001). The five-variable nomogram achieved AUCs of 0.85 and 0.81 in the derivation and validation cohorts, respectively, outperforming SOFA and APACHE II scores, with favorable calibration and greater clinical net benefit. Intra-individual ACT and APTT variability may therefore provide accessible prognostic information for early risk stratification and individualized anticoagulation management in ECMO patients.