aPC with cofactor protein S (PS) and fV inhibits the EPCR-dependent activation of the inflammatory PAR2 signaling by destabilizing the ternary TF-VIIa-Xa complex. Without the R506 cleavage site, fV Leiden (FVL) loses its cofactor activity to facilitate aPC inhibition of the inflammatory signaling. Professional illustration by Somersault18:24.