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Human monocytes support factor X activation by factor VIIa, independent of
tissue factor: implications for the therapeutic mechanism of high- dose
factor VIIa in hemophilia [see comments]
M Hoffman, DM Monroe and HR Roberts
Department of Pathology, Durham Veterans Affairs Medical Center, NC 27705.
High doses of recombinant factor VIIa are useful in managing bleeding in
hemophiliacs with inhibitors. Whether this therapeutic effect of factor
VIIa is dependent on tissue factor (TF) is a matter of debate. We examined
the ability of freshly isolated human monocytes (which lack TF) to support
the activation of coagulation-factor X by factor VIIa. The rate of factor-X
activation by factor VIIa was accelerated in the presence of monocytes
compared with the rate of X activation in solution. This activation of
factor X on monocytes was saturable with a K1/2 of about 400 to 600 pmol/L
factor VIIa. The rate of activation was not inhibited by an excess of
inhibitory anti-TF antibody or a Gla- containing fragment of prothrombin.
In contrast to monocytes, an endothelial cell line did not support
activation of factor X by factor VIIa. Our findings suggest that at least
one cell type can accelerate activation for factor X by factor VIIa in the
absence of TF. This activity requires higher concentrations of factor VIIa
than does the TF mechanism. The concentrations of VIIa required are of a
similar order of magnitude to those required for a therapeutic effect of
VIIa in bleeding hemophiliacs with inhibitors.
Volume 83,
Issue 1,
pp. 38-42,
01/01/1994
Copyright © 1994 by The American Society of Hematology
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