Effect of APC on thrombin generation in models of coagulation.

Each of the reactions contained plasma concentrations of zymogen procoagulant factors, unactivated coagulation cofactors, and coagulation inhibitors, including protein S as described in “Materials and methods” and shown in Table 1. APC was added to each reaction at none, 3.25 nM, 6.5 nM, 13 nM, and 65 nM, respectively. Note that the x-axis (thrombin generation) and y-axis (time) scales differ somewhat between experiments. The results in panel A and panel D are representative of experiments using platelets from at least 4 different individuals. (A) Tissue factor was derived from cultured monocytes treated with lipopolysaccharide. Unactivated platelets were added at 100 000/μL. Data for 3.25 nM, 6 nM, and 13 nM overlie the data for 0 and 65 nM APC and are not shown. (B) Tissue factor (100 pM) was incorporated into phospholipid vesicles (PC/PE/PS, 41:44:15). Results at 65 nM are identical to results at 13 nM and are not shown. (C) Tissue factor (10 pM) was incorporated into phospholipid vesicles (PC/PE/PS, 41:44:15). Results at 65 nM are not shown and are identical to results at 13 nM. (D) Tissue factor was derived from cultured HMVECs. Unactivated platelets were added at 100 000/μL. Results at 3.25 nM and 6.5 nM are intermediate between no APC and 13 nM APC and are not shown.