Daily biomarker trajectories predict major bleeding in patients on venovenous ECMO for ARDS: a retrospective longitudinal cohort study

Bleeding complications during venovenous extracorporeal membrane oxygenation (ECMO) remain a leading cause of morbidity, yet granular longitudinal data linking daily biomarker dynamics to bleeding around circuit exchanges are scarce. We analyzed 93 exchanges from 35 severe acute respiratory distress syndrome (ARDS) patients (2020–2022) across 15-day peri-exchange windows in this retrospective single-center cohort study. Major bleeding (defined by ELSO criteria) occurred on 100/1317 observation-days (7.6%), clustering peri-exchange (13.1% vs. 4.2% outside ± 2 days, p < 0.001). Using generalized linear mixed models (GLMMs) with nested random effects, we characterized coagulation trajectories and bleeding predictors. White blood cell count was the strongest predictor (OR 2.00/SD, 95% CI 1.43–2.82, p < 0.001), followed by platelets (OR 0.58, p = 0.014) and fibrinogen (OR 0.60, p = 0.035). Time-lagged GLMMs identified D-dimer and fibrinogen as early warning markers 1–2 days pre-bleeding. Circuit exchange shortened bleeding duration (HR 2.23, 95% CI 1.16–4.29, p = 0.017). D-dimer rose pre-exchange and declined post-exchange, while fibrinogen and platelets showed inverse patterns, suggesting consumptive coagulopathy reversed by exchange. White blood cell trajectories implicated independent inflammatory risk. These findings demonstrate a 1–2 days predictive time window for any action needed to counteract or prevent major bleeding, supporting biomarker-guided circuit management and hemostatic strategies in ECMO.