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Updated: Jul 2, 2026
03:53
Extracellular Vesicle Tissue Factor Activity Assay
Published on: December 29, 2023
Protein S is a cofactor for tissue factor pathway inhibitor.
J Rosing1, L F A Maurissen, S N Tchaikovski
1Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. j.rosing@bioch.unimaas.nl
Thrombosis Research
|August 12, 2008
Summary
Protein S enhances the anticoagulant activity of Tissue Factor Pathway Inhibitor (TFPI), independent of APC. This TFPI cofactor activity is reduced in oral contraceptive users, potentially increasing thrombosis risk.
Area of Science:
- Biochemistry
- Hematology
- Molecular Biology
Background:
- Protein S is a vitamin K-dependent protein with known anticoagulant functions as a cofactor for Activated Protein C (APC).
- Protein S also exhibits anticoagulant activity independently of APC, suggesting additional roles in hemostasis.
Purpose of the Study:
- To investigate the novel anticoagulant mechanism of Protein S involving Tissue Factor Pathway Inhibitor (TFPI).
- To quantify the functional activity of the TFPI/Protein S system in plasma and assess its impairment in specific populations.
Main Methods:
- Thrombin generation experiments were performed in normal plasma and plasma deficient in TFPI and/or Protein S.
- Kinetic analysis using purified proteins elucidated the interaction between Protein S and TFPI.
- Calibrated automated thrombography was employed to develop assays for TFPI/Protein S system activity.
Main Results:
- Protein S was demonstrated to stimulate TFPI-mediated inhibition of Tissue Factor (TF) by enhancing the formation of the FXa:TFPI complex, reducing TFPI's Ki from 4 nM to 0.5 nM.
- This enhancement of TFPI activity by Protein S requires full-length TFPI and a negatively charged phospholipid surface.
- The TFPI/Protein S system activity was found to be significantly impaired in oral contraceptive users.
Conclusions:
- Protein S functions not only as an APC cofactor but also as a cofactor for TFPI, contributing to the regulation of the extrinsic pathway of coagulation.
- Reduced TFPI cofactor activity due to Protein S deficiency may contribute to the heightened risk of venous thrombosis.
- The developed assays provide a means to assess the functional status of the TFPI/Protein S system, revealing its impairment in oral contraceptive users.
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