Increased TF procoagulant activity in response to exogenous and endogenously generated APC requires EPCR binding but not PAR1 cleavage. TNFα-induced (5 hours) cells were treated for the final 3 hours with the indicated agonists. Blocking anti-EPCR (RCR-252, 25 μg/mL), nonblocking anti-EPCR (RCR-92, 25 μg/mL), cleavage blocking anti-PAR1 (ATAP2 and WEDE15, 10 and 25 μg/mL, respectively), and anti–protein C (C1, 25 μg/mL) were added 30 minutes before the agonists. Factor Xa generation is shown in panels A and B. For the experiments shown in panel B, APC activity in the cell medium at the end of the incubation time was also analyzed. No amidolytic activity was detected in the absence of protein C and only the results in the presence of protein C are shown. Means ± SEM; n = 5 (A) and 9 (B). **P < .005 compared with the corresponding sample without APC or protein C.