Effects of factor VII and factor VIIa in the absence of factor VIII.

The effects of factor VII and factor VIIa under hemophilia A conditions (without factor VIII) were studied on TF-dependent (5 small pMTF) thrombin generation in the presence of TFPI and AT-III as described in Figure 3. Panel A shows thrombin generation curves in the presence of the physiologic ratio of factor VIIa:factor VII (100 pmol/L:10 nmol/L) in the absence (○) or presence (•) of factor VIII. Omission of factor VII from the reaction in the absence of factor VIII (panel A, □) results in a considerable increase in the rate of thrombin generation. Addition of 10 nmol/L factor VIIa to the reaction with factor VII and absence of factor VIII (panel A, ⋄) results in a normalization of the thrombin generation profile. Panel B displays thrombin generation curves, from the contemporaneous experiment shown in panel A, which were performed in the absence of factor VIII and presence of 10 nmol/L factor VII with a range of factor VIIa concentrations, namely, 0.1 (▿), 0.5 (*), 1 (♦), 2 (▴), 0.5 (▪), and 10 nmol/L (•). Panel C shows the maximal observed rates thrombin generation in curves shown in panel A as a function of the factor VIIa concentration; absence and presence of factor VIII and factor VII are indicated in the figure in panel C.