The influence of APC and protein S on thrombin generation in plasma. Thrombin generation was initiated with 3.5 pM tissue factor, 10 μM phospholipid vesicles (20/60/20 DOPS/DOPC/DOPE), and 16 mM CaCl₂ (final concentrations) in normal pooled plasma in the absence of APC and antibodies against protein C and protein S (○) or in the presence of antibodies against protein C (•), antibodies against both protein C and protein S (▪), 5 nM APC (▴), or 5 nM APC and antibodies against protein C (▵). Thrombin generation was quantified with the fluorogenic substrate I-1140 as described in “Materials and methods.” Inset: Thrombin generation was initiated under the same conditions in plasma in the presence of antibodies against protein C without (•) or with (▪) monoclonal antibodies CLB-PS13 against the Gla domain of protein S.