Both authors contributed equally to this work.
Polyphosphate binds to human von Willebrand factor in vivo and modulates its interaction with glycoprotein Ib
Article first published online: 30 OCT 2012
© 2012 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 10, Issue 11, pages 2315–2323, November 2012
How to Cite
MONTILLA, M., HERNÁNDEZ-RUIZ, L., GARCÍA-COZAR, F. J., ALVAREZ-LADERAS, I., RODRÍGUEZ-MARTORELL, J. and RUIZ, F. A. (2012), Polyphosphate binds to human von Willebrand factor in vivo and modulates its interaction with glycoprotein Ib. Journal of Thrombosis and Haemostasis, 10: 2315–2323. doi: 10.1111/jth.12004
- Issue published online: 30 OCT 2012
- Article first published online: 30 OCT 2012
- Accepted manuscript online: 24 SEP 2012 09:31PM EST
- Received 9 March 2012, accepted 13 September 2012
- von Willebrand disease;
- von Willebrand factor
Summary. Background: Polyphosphate, a phosphate polymer released by activated platelets, has recently been described as a potent modulator of blood coagulation and fibrinolysis. In blood plasma, polyphosphate binds to and alters the biological functions of factor XII, fibrin(ogen), thrombin and factor VII activating protease.
Objectives: The aim of the present study is to investigate whether polyphosphate also binds to von Willebrand factor (VWF) and alters some of its activities.
Methods/Results: When studying patients with type 1 von Willebrand disease (VWD) and their healthy relatives, we discovered a significant correlation between von Willebrand factor (VWF) and platelet polyphosphate levels. We have also found polyphosphate in preparations of VWF isolated from normal platelets and plasma. Surface plasmon resonance and electrophoretic mobility assays indicated that polyphosphate interacts with VWF in a dose- and time-dependent manner. Treatment of normal plasma with active exopolyphosphatase decreased the VWF ristocetin cofactor (VWF:RCo) activity, a functional measure of VWF binding to platelet glycoprotein receptor Ib. VWF collagen binding and multimerization were unaltered after polyphosphate depletion. Moreover, addition of polyphosphate increased the deficient VWF:RCo activity presented by plasma from patients with type 1 VWD.
Conclusions: Our results reveal that a new role is played by polyphosphate in hemostasis by its interaction with VWF, and suggest that this polymer may be effective in the treatment of some types of VWD.