Influence of the protein C pathway on protease-induced thrombin generation in hemophilic plasma. Protease induced thrombin generation in HA plasma was measured for 90 minutes at 37°C in the presence of increasing amounts of sTM (red, 0; orange, 1.0; green, 2.5; blue, 5.0; purple, 10.0; dark red, 15.0; and black, 20.0nM). In each panel, HA plasma was incubated with the indicated protease (A, wt-FXa, 30pM and B, FXa^I16L, 10pM) and 2.0pM TF/4μM phospholipid. Thrombin generation was initiated with CaCl₂ and a thrombin fluorogenic substrate as detailed in “Methods.” In panel C, the total ETP remaining for the indicated protease was plotted versus the sTM concentration (wt-FXa [■]; FXa^I16L [●], and rFXa^V17A [▴]). The results are expressed as percent residual activity where 100% is the maximal ETP in the absence of sTM for a given protease. With use of this experimental setup, the initial ETP for each protease is similar. In each of the panels, the lines are arbitrarily drawn. The data are representative of 3 similar experiments.