Clinical correlates for major bleeding during veno-arterial extracorporeal membrane oxygenation support: a time-dependent perspective

Major bleeding is a common and serious complication of veno-arterial extracorporeal membrane oxygenation (VA ECMO). Current perspectives on bleeding risk fail to reflect dynamic changes over time in bleeding incidence and risk factors for bleeding. All adults receiving VA ECMO (2016–2023) for cardiac failure in 6 participating Dutch centers were included in a prospective cohort. Major bleeding was defined as bleeding requiring surgical or radiological intervention and/or transfusion of > 3 red blood cell units within 24 h. Bleeding cases were matched up to 4 controls who had not (yet) bled at that timepoint. Generalized additive models were applied to visualize trajectories of coagulation, inflammatory, and perfusion markers, exploring temporal differences between bleeding cases and matched controls. Among 558 VA ECMO supported patients, 232 (42%) experienced ≥ 1 major bleeding event, totaling 342 episodes (incidence rate 112 per 1000 days at risk). Most bleeding events occurred early (< 48 h; n = 190, 56%), primarily at the cannulation site (37%) and intrathoracically (38%). Fewer events occurred later (> 48 h; n = 152, 44%), predominantly intrathoracically (53%). Female sex and lower body weight (both p < 0.01) were associated with bleeding. Compared with controls, patients who developed bleeding showed increased activated partial thromboplastin time, prothrombin time, heparin ratio, anti-factor Xa and international normalized ratio preceding bleeding, whereas platelet count, hemoglobin and leukocytes were lower. Bleeding was associated with higher intensive care mortality (HR 1.39, 95% CI 1.09–1.76, p < 0.01). A severe major bleeding developed in nearly half of all patients and was associated with an increased mortality risk. The trajectories of coagulation and inflammatory markers observed in patients with versus without bleeding events underscore the dynamic nature of bleeding risk and highlight future opportunities for dynamic bleeding risk prediction during VA ECMO.