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Thromb Haemost 2001; 85(05): 761-765
DOI: 10.1055/s-0037-1615714
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Schattauer GmbH

C4b-binding Protein Inhibits the Factor V-dependent but not the Factor V-independent Cofactor Activity of Protein S in the Activated Protein C-mediated Inactivation of Factor VIIIa

Robbert H. L. van de Poel
1   Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Center, Utrecht, Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
,
Joost C. M. Meijers
1   Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Center, Utrecht, Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
2   Present address: Dr. J. C. M. Meijers, Department of Vascular Medicine, Academic Medical Center, 1100 DD Amsterdam, The Netherlands
,
Bonno N. Bouma
1   Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Center, Utrecht, Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 14 July 2000

Accepted after resubmission 22 December 2000

Publication Date:
11 December 2017 (online)

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Summary

Activated protein C (APC) is an important inactivator of coagulation factors Va and VIIIa. In the inactivation of factors Va and VIIIa, protein S serves as a cofactor to APC. Protein S can bind to C4b-binding protein (C4BP), and thereby loses its cofactor activity to APC. By modulating free protein S levels, C4BP is an important regulator of protein S cofactor activity. In the factor VIIIa inactivation, protein S and factor V act as synergistic cofactors to APC. We investigated the effect of C4BP on both the factor V-independent and factor V-dependent cofactor activity of protein S in the factor VIIIa inactivation using a purified system. Protein S increased the APC-mediated inactivation of factor VIIIa to 60% and in synergy with protein S, factor V at equi-molar concentrations increased this effect further to 90%. The protein S/factor V synergistic effect was inhibited by preincubation of protein S and factor V with a four-fold molar excess of C4BP. However, C4BP did not inhibit the factor V-independent protein S cofactor activity in the purified system whereas it inhibited the cofactor activity in plasma. We conclude that C4BP-bound protein S retains its cofactor activity to APC in the factor VIIIa inactivation.

Keywords

C4b-binding protein - protein S - factor VIII - protein C - factor V
 

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