DETERMINANTS OF COAGULATION ACTIVATION IN HUMANS

To evaluate the mechanism responsible for the generation of factor VII a in vivo, we measured the levels of this enzyme after administering p urified factor IX concentrates to patients with hemophilia B. Their fa ctor VIIa levels were initially very low and gradually increased to no rmal, but there were no significant changes in the generation of facto r Xa or thrombin, The administration of 10 mu g/kg body weight of reco mbinant factor VIIa to patients with factor VII deficiency increased t he circulating levels 35-fold, but this only resulted in normalization of the activation of factor IX and factor X. Our data indicate that f actor IXa is primarily responsible for the basal levels of free factor VIIa in vivo, and that changes in free factor VIIa in the blood do no t necessarily lead to alterations in factor X activation.