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

BACKGROUND

Bleeding and thrombosis remain leading causes of morbidity and mortality in patients supported by extracorporeal membrane oxygenation (ECMO).

OBJECTIVES

To assess hemostatic changes during veno-venous (VV)-ECMO support after respiratory failure due to viral pneumonia and their association with major bleeding, thrombosis, and mortality.

METHODS

Coagulation factors (factors [F]II, FV, FVII, FVIII, FIX, FX, FXI, FXII), von Willebrand profile, and thrombin generation (TG) were measured at cannulation, during VV-ECMO (every fifth day), 1 hour, and 24 hours after decannulation in 50 patients (August 2018-January 2020).

RESULTS

Median age was 47 (18-68) years, 56% were men, and median VV-ECMO duration was 9 (3-41) days. Intracranial hemorrhage and ischemic stroke were detected in 10% and 4%, respectively, within 24 hours of initiating VV-ECMO. The 180-day mortality was 10%; 58% developed thrombosis and 28% major bleeding (43% were intracranial hemorrhage). Coagulation factor levels fell significantly within 24 hours 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 level increased throughout VV-ECMO and correlated with reduced (r = -0.54, P < .001) and delayed (r = 0.6, P < .001) TG. The von Willebrand factor (VWF) Ristocetin cofactor activity (VWF:RCo)/VWF antigen (VWF:Ag) ratio was significantly reduced by 24 hours of initiation and during VV-ECMO compared to precannulation. In multivariate analyses, older age, thrombocytopenia, increased creatinine level, and reduced TG at cannulation were associated with mortality. VWF:RCo/VWF:Ag ratio <0.7 and low TG (< 500 nM·min) at precannulation predicted major bleeding while raised fibrinogen level and TG increased thrombotic risk. Major bleeding was associated with increased mortality (3.6-fold) while thrombosis had no impact.

CONCLUSION

Precannulation reduced TG (<500 nM·min), reduced VWF:RCo/VWF:Ag ratio and increased tissue factor pathway inhibitor alpha levels had significant impacts on major bleeding, which was associated with increased mortality.