Activation of Human Factor VII in Plasma and in Purified Systems: ROLES OF ACTIVATED FACTOR IX, KALLIKREIN, AND ACTIVATED FACTOR XII

Factor VII can be activated, to a molecule giving shorter clotting times with tissue factor, by incubating plasma with kaolin or by clotting plasma. The mechanisms of activation differ. With kaolin, activated Factor XII (XII_a) was the apparent principal activator. Thus, Factor VII was not activated in Factor XII-deficient plasma, was partially activated in prekallikrein and high-molecular weight kininogen (HMW kininogen)-deficient plasmas, but was activated in other deficient plasmas. After clotting, activated Factor IX (IX_a) was the apparent principal activator. Thus, Factor VII was not activated in Factor XII-,HMW kininogen-, XI-, and IX-deficient plasmas, but was activated in Factor VIII-, X-, and V-deficient plasmas. In further studies, purified small-fragment Factor XII_a (β-XII_a), kallikrein, and Factor IX_a were added to partially purified Factor VII and to plasma. High concentrations of β-XII_a activated Factor VII in a purified system; much lower concentrations of β-XII_a activated Factor VII in normal plasma but not in prekallikrein or HWM kininogen-deficient plasmas. Kallikrein alone failed to activate partially purified Factor VII but did so when purified Factor IX was added. Kallikrein also activated Factor VII in normal, Factor XII-, and Factor IX-deficient plasmas. Purified Factor IX_a activated partially purified Factor VII and had no additional indirect activating effect in the presence of plasma. These results demonstrate that both Factor XII_a and Factor IX_a directly activate human Factor VII, whereas kallikrein, through generation of Factor XII_a and Factor IX_a, functions as an indirect activator of Factor VII.

Click on an image below to see the page. View PDF of the complete article

page 1056

page 1057

page 1058

page 1059

page 1060

page 1061

page 1062

page 1063

page 1064

page 1065