A new regulatory function of activated factor V: inhibition of the activation by tissue factor/factor VII(a) of factor X
Version of Record online: 13 MAR 2013
© 2013 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 11, Issue 3, pages 503–511, March 2013
How to Cite
A new regulatory function of activated factor V: inhibition of the activation by tissue factor/factor VII(a) of factor X. J Thromb Haemost 2013; 11: 503–11., , , , .
- Issue online: 13 MAR 2013
- Version of Record online: 13 MAR 2013
- Accepted manuscript online: 7 JAN 2013 12:34PM EST
- Manuscript Accepted: 2 JAN 2013
- Manuscript Received: 3 AUG 2012
- factor Va;
- factor VII;
- factor Xa;
- thrombin generation;
- tissue factor
We observed that minute amounts of thrombin or the enzyme Russell's viper venom activating factor V (RVV-V) added to plasma strongly diminish the potential of that plasma to generate thrombin after being triggered by tissue factor.
To find the mechanism behind this phenomenon.
Methods and Results
Thrombin generation (TG) initiated by tissue factor (TF) is strongly and dose-dependently inhibited by addition of activated factor V (FVa) or by addition of a factor V activator (thrombin or RVV-V). No inhibition is seen when TG is triggered via the intrinsic pathway or by direct activation of factor X. The effect is independent of proteins C and S and tissue factor pathway inhibitor (TFPI). In factor VII-deficient plasma the effect is seen when it is spiked with recombinant factor VII (FVII) and to a much lesser extent when spiked with recombinant FVIIa. In a purified system, FVa also dose-dependently inhibits the activation of FX by TF/FVII(a). The inhibitory effect is neutralized by antibodies against the light chain of FVa but not by antibodies against the heavy chain.
Our observations can be explained by assuming that FVa, via its light chain, binds to the complex TF/FVII(a) and prevents it from activating FX. We assume that this mechanism reduces the possibility that thrombin and factor Xa escaping from a wound area into the circulation, together with blood-borne tissue factor, would trigger intravascular coagulation.