The role of ^superFVa and APC’s anticoagulant activity on the DOAC mediated inhibition of thrombin generation on endothelial cells. Thrombin generation was performed on EA.hy926 endothelial cells using human plasma in the absence of exogenously added tissue factor or phospholipids. (A) Thrombin generation on EA.hy926 endothelial cells in the presence of antibodies (α) against (A)PC (C1), TM, or EPCR (all 50 μg/mL) or ^superFVa (200 nM). (B) Thrombin generation in the presence and absence of EA.hy926 endothelial cells with different concentrations apixaban, rivaroxaban, or dabigatran. Thrombin generation in the absence of cells was initiated by 0.2 pM tissue factor and 4 μM phospholipid vesicles (PC/PS 80/20). (C) Panel A in the presence of apixaban (200 nM). (D) Panel A in the presence of rivaroxaban (200 nM). (E) Panel A in the presence of dabigatran (200 nM). (F) Lag time of thrombin generation on EA.hy926 endothelial cells was determined in the presence of all 3 direct oral anticoagulants (200 nM) with and without antibodies against (A)PC (50 μg/mL) or ^superFVa (200 nM). ns, not significant; TM, thrombomodulin.