Involvement of face 1 and face 2 PS residues for APC cofactor activity in purified systems. Wild-type rPS (▪), F1_FII-Gla_PS-PS (▴), F2_FII-Gla_PS-PS (▾), and F12_PS-Gla_FII-PS (○) were assessed in the FVa (A) and FVIIIa (B) inactivation assays, as described in Figure 4. In both inactivation assays, the effect of APC alone (*) on thrombin (A) and FXa (B) generation was also measured. As in the plasma clotting assays, APC cofactor activity was lost in F1_FII-Gla_PS-PS and F2_FII-Gla_PS-PS and was restored in the PS mutant F12_PS-Gla_FII-PS.