Association of coagulation dysfunction with thrombosis, bleeding and mortality in patients supported by veno-venous extracorporeal membrane oxygenation for viral pneumonia

Bleeding and thrombosis remain leading causes of morbidity and mortality in patients supported by extracorporeal membrane oxygenation (ECMO). Assess haemostatic changes during veno-venous (VV)-ECMO support after respiratory failure due to viral pneumonia and their association with major bleeding, thrombosis and mortality. Coagulation factors (II, V, VII, VIII, IX, X, XI, XII), von-Willebrand profile and thrombin generation (TG) were measured at cannulation, during VV-ECMO (every 5th day), 1hr and 24hrs-post decannulation in 50 patients (Aug 2018-Jan 2020). Median age was 47 (18-68)years, 56% were men and median VV-ECMO duration was 9 (3-41)days. Intracranial haemorrhage (ICH) and ischaemic stroke occurred in 10% and 4%, respectively, within 24hrs of initiating VV-ECMO. The 180-day mortality was 10%; 58% developed thrombosis and 28% major bleeding (43% were ICH). Coagulation factors fell significantly within 24hrs of initiating VV-ECMO but returned to normal by day 5. TG decreased significantly throughout VV-ECMO, with nadir at decannulation. Tissue factor pathway inhibitor alpha (TFPIα) rose throughout VV-ECMO and correlated with reduced (r=-0.54, p<0.001) and delayed (r=0.6, p<0.001) TG. VWF:RCo/VWF:Ag was significantly reduced. In multivariate analyses increasing age, thrombocytopenia, raised creatinine and reduced TG at cannulation were associated with mortality. VWF:RCo/VWF:Ag ratio <0.7 and low TG (<500nM•min) at pre-cannulation predicted major bleeding whilst raised fibrinogen and TG increased thrombotic risk. Major bleeding was associated with increased mortality (3.6-fold) whilst thrombosis had no impact. Pre-cannulation reduced TG (<500nM•min) and VWF:RCo/VWF:Ag with raised TFPIα had significant impact on major bleeding which was associated with increased mortality.