Determinants of plasma factor VIIa levels in humans
S Eichinger, PM Mannucci, F Tradati, AA Arbini, RD Rosenberg and KA Bauer
Department of Medicine, Brockton-West Roxbury Department of Veterans
Affairs Medical Center, Boston, MA, USA.
Several enzymes can activate factor VII in vitro, but the protease
responsible for generating factor VIIa in vivo has not been determined.
Using recombinant tissue factor that has undergone a COOH-terminal
truncation, a sensitive functional assay has been established for measuring
plasma factor VIIa levels. To evaluate the mechanism responsible for the
generation of factor VIIa in vivo, we measured the levels of this enzyme
after administering purified concentrates of factor IX and factor VIII to
patients with severe deficiencies of these clotting factors. In patients
with hemophilia B, factor VIIa levels were initially reduced to 0.5 +/- 0.1
ng/mL and gradually increased to normal after infusing 100 U/kg of body
weight (BW) of factor IX. Despite these increases, there were no
significant changes in the generation of factor Xa or thrombin. In patients
with hemophilia A, only a slight reduction in factor VIIa levels (2.5 +/-
1.3 ng/mL) was observed as compared with controls (3.3 +/- 1.1 ng/mL) and
no significant changes were observed after factor VIII levels were
normalized. The administration of recombinant factor VIIa (10 micrograms/kg
BW) to patients with factor VII deficiency increased the mean circulating
level of the enzyme to 118 ng/mL, but this only resulted in normalization
of the levels of the activation peptides of factor IX and factor X. The
above data indicate that factor IXa is primarily responsible for the basal
levels of free factor VIIa generated in vivo (ie, in the absence of
thrombosis or provocative stimuli) and that changes in the plasma
concentrations of free factor VIIa in the blood do not necessarily lead to
alterations in the extent of factor X activation.
Volume 86,
Issue 8,
pp. 3021-3025,
10/15/1995
Copyright © 1995 by The American Society of Hematology
