Effect of factor VII on thrombin generation in the presence of TFPI and AT-III.

The effect of zymogen factor VII on TF-dependent thrombin generation was investigated as described in Figure 1, except that the natural coagulation inhibitors TFPI and AT-III were present at their respective plasma concentrations in the final reaction mixture. Reactions were initiated by 10 (panel A), 20 (panel B), or 100 (panel C) pmol/L TF in the presence of 100 pmol/L factor VIIa in the absence (□) or presence (▪) of 10 nmol/L factor VII. In the presence of TFPI and AT-III the inhibitory effect of factor VII on TF-dependent thrombin generation is not only restricted to the initial part of the reaction, but also decreases the maximal observed thrombin generation in reactions initiated by TF concentrations of ≤ 20 pmol/L. At TF concentrations of 100 pmol/L and higher thrombin generation occurs explosively, regardless of the presence of inhibitors or zymogen factor VII.