Elevated von Willebrand Factor Antigen is an Early Predictor of Mortality and Prolonged Length of Stay for Coronavirus Disease 2019 (COVID-19) Inpatients

Cotter, Alexander H; Yang, Su-Jau T; Shafi, Hedyeh; Cotter, Timothy M; Palmer-Toy, Darryl Erik

CONTEXT: Coagulation factor and endothelial injury marker, von Willebrand factor antigen (vWF:Ag), is elevated in coronavirus disease 2019 (COVID-19). OBJECTIVE: To assess prognostic value of vWF:Ag for COVID-19 inpatients. DESIGN: Citrated plasma samples collected from COVID-19 inpatients for D-dimer measurement were tested for vWF:Ag. Measurements of vWF:Ag and common acute phase reactants (APRs) were correlated with clinical outcomes and length of stay (LOS). RESULTS: We included 333 samples from a diverse group of 120 COVID-19 inpatients. There was a clear association of higher peak measurements of vWF:Ag and other APRs with adverse clinical outcomes. Peak vWF:Ag >300% was associated with a 5-fold increased risk of death (Odds Ratio 5.08, P<.001) and a 30-fold increased risk of prolonged (>4 days) LOS (OR 29.65, P =.001). Peak D-dimer >3.8 FEU mg/L was associated with a 15-fold increase in risk of death (OR 14.73, P <.001) and a 5-fold increased risk of prolonged LOS (OR 4.55, P=.02). Using the earliest paired measurements of vWF:Ag and D-dimer from each patient and the same cut-offs, vWF:Ag was associated with a 3.5-fold increase in risk of death (OR 3.54, P=.004) and a 20-fold risk of prolonged LOS (OR 20.19, P=.004). Yet D-dimer was not significantly associated with either death (OR 1.9, P=.29) or prolonged LOS (OR 1.02, P=.98). CONCLUSIONS: Both peak and early post-admission vWF:Ag >300% were highly predictive of death and prolonged length of stay among COVID-19 inpatients. Measurement of vWF:Ag may prove a valuable tool to guide escalation of COVID-19 treatment, particularly anticoagulation.