Summary
Tissue factor (TF) functions as the receptor and cofactor for factor VIIa (VIIa) to
form a proteolytically active TFVIIa complex on cell surfaces. We here demonstrate
that most MAbs against human TF were poor inhibitors of TF function in plasma and
that they inhibited preformed TF-VIIa complex at a slow rate which was dependent on
dissociation of VIIa from the cell surface TF. An exception was defined by one MAb
(TF8-5G9) which was an effective immediate anticoagulant in plasma. Binding of TF8-5G9
to TF-VIIa inhibited catalytic function prior to dissociation of the TF-VIIa complex.
This analysis thus establishes two distinct mechanisms by which MAbs interfere with
TF function. The MAb TF8-5G9 introduces a therapeutic principle for rapid arrest of
inappropriate triggering of coagulation by TF as well as the TF-VIIa complex in vivo.
