Activation of coagulation factor VII by tissue-type plasminogen activator

To investigate the effect of tissue-type plasminogen activator (t-PA) on bl ood coagulation, we examined the effects of the addition of t-PA to normal pool plasma (NPP) on clotting times such as diluted prothrombin time (PT) a nd kaolin clotting time (KCT). The diluted PT but not the KCT was significa ntly shortened by the addition of t-PA to NPP compared with the normal cont rols, suggesting a t-PA-induced activation of blood coagulation through fac tor VII (FVII) activation. The activated factor VII (FVIIa) concentration i n the NPP was significantly increased by the addition of t-PA, Although the FVIIa formation was not observed following the incubation of purified FVII with only t-PA or plasminogen, an increase in the FVIIa level was observed after the incubation of purified FVII with t-PA together with plasminogen, or only plasmin. This plasmin-mediated FVIIa formation was also confirmed by Western blotting. These findings suggest that t-PA enhances the activati on of the coagulation system through FVII activation. (C) 1999 Wiley-Liss, Inc.