![Figure 1. Impact of competition between FVII and FVIIa for TF. Thrombin generation was measured in FVII-deficient, FVIII-neutralized plasma supplemented with rFVIIa in the absence or presence of FVII or FVIIR152A and initiated with 1 pM TF (Innovin) unless otherwise stated. (A) The effect of the presence of 10 or 100 nM FVII with 0.1 to 25 nM rFVIIa. The degree of inhibition of thrombin generation was calculated at each [rFVIIa] as the decrease in thrombin peak level compared with a sample without added FVII. The FVIIa present in FVII (0.3%) was taken into account when 100 nM FVII was used at a total FVIIa concentration <6 nM. Data are mean of repeated experiments (n = 2 or 3). (B) The effect of FVII, FVIIR152A, and reduced TF level on the thrombin generation profile at 25 nM rFVIIa. The curves represent the thrombin generation obtained in the presence of rFVIIa alone initiated with either 1 pM TF (thick solid line) or 1/5 pM TF (dotted line) or initiated with 1 pM TF in the presence of either 100 nM FVII (thin solid line) or 100 nM FVIIR152A (dashed line). (C) The effect of FVII, FVIIR152A, and reduced TF level on the thrombin generation profile at 6 nM FVIIa. Same setup as in B, but initiation was with 1/15 pM TF in the low-TF sample (dotted line). (D) The effect of endogenous level (10 nM) of FVII on the thrombin generation profile at therapeutic concentrations of rFVIIa. Thin solid and dotted lines depict the results with 6 nM rFVIIa, and thick solid and dashed lines are the corresponding results with 25 nM rFVIIa, in the absence and presence of 10 nM FVII, respectively. The presence of 100 nM FVIIR152A together with 6 or 25 nM FVIIa reduced the functional TF density as measured by a significant decrease in the thrombin generation, but still no inhibitory effect of 10 nM zymogen FVII could be revealed (data not shown). In B-D, the thrombin generation profiles were normalized for easier comparison, and a peak level of 1 was assigned to the samples initiated with 1 pM TF without added zymogen FVII. Data are mean of repeated experiments (n = 3).](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/124/20/10.1182_blood-2014-05-576892/4/3172f1.jpeg?Expires=1735849896&Signature=lpPiduI3CJTA3ww7FimGc5QgCDRP468h-9OM5lIYINBg2658QuibeUFv77VE0BcfHqvU4r3W9W2g6ysTLokp6Z~Dgzj1lZc3sYBXwORSW84~0n2z0mnTDAKLUNbWqqm1aPpatC0tYpmstwg0Y9g7xwdEI6tQ4DMtlgC3oPfhbbwlZY7-3aXBinhutuWS1jexr9MRS1QMEqNz2PfKLhVJ5lkBqKCL7LgBs8YgsBMA858ob8n7-zpyUEcAp73iIaGKv8T6aGvaz5~qkDeMoRXp7acakUE9~hClPBxI5IrVXf2dQVQrCavklm-OkIYF5PhxpRa3CvVq2uH40GfOwR2GVw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Impact of competition between FVII and FVIIa for TF. Thrombin generation was measured in FVII-deficient, FVIII-neutralized plasma supplemented with rFVIIa in the absence or presence of FVII or FVIIR152A and initiated with 1 pM TF (Innovin) unless otherwise stated. (A) The effect of the presence of 10 or 100 nM FVII with 0.1 to 25 nM rFVIIa. The degree of inhibition of thrombin generation was calculated at each [rFVIIa] as the decrease in thrombin peak level compared with a sample without added FVII. The FVIIa present in FVII (0.3%) was taken into account when 100 nM FVII was used at a total FVIIa concentration <6 nM. Data are mean of repeated experiments (n = 2 or 3). (B) The effect of FVII, FVIIR152A, and reduced TF level on the thrombin generation profile at 25 nM rFVIIa. The curves represent the thrombin generation obtained in the presence of rFVIIa alone initiated with either 1 pM TF (thick solid line) or 1/5 pM TF (dotted line) or initiated with 1 pM TF in the presence of either 100 nM FVII (thin solid line) or 100 nM FVIIR152A (dashed line). (C) The effect of FVII, FVIIR152A, and reduced TF level on the thrombin generation profile at 6 nM FVIIa. Same setup as in B, but initiation was with 1/15 pM TF in the low-TF sample (dotted line). (D) The effect of endogenous level (10 nM) of FVII on the thrombin generation profile at therapeutic concentrations of rFVIIa. Thin solid and dotted lines depict the results with 6 nM rFVIIa, and thick solid and dashed lines are the corresponding results with 25 nM rFVIIa, in the absence and presence of 10 nM FVII, respectively. The presence of 100 nM FVIIR152A together with 6 or 25 nM FVIIa reduced the functional TF density as measured by a significant decrease in the thrombin generation, but still no inhibitory effect of 10 nM zymogen FVII could be revealed (data not shown). In B-D, the thrombin generation profiles were normalized for easier comparison, and a peak level of 1 was assigned to the samples initiated with 1 pM TF without added zymogen FVII. Data are mean of repeated experiments (n = 3).
