Related Experiment Video
Updated: May 24, 2026

Extracellular Vesicle Tissue Factor Activity Assay
Published on: December 29, 2023
TFPI-dependent activities of protein S
Sameera Peraramelli1, Jan Rosing, Tilman M Hackeng
1Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University Maastricht, The Netherlands.
Abstract:
Protein S is an essential anticoagulant protein that acts as a cofactor for full length tissue factor pathway inhibitor (TFPI) and activated protein C (APC) in the down regulation of coagulation. Protein S enhances APC-mediated inactivation of the coagulation factors Va and VIIIa, and it stimulates inhibition of factor (F)Xa by TFPI. Because TFPI is a tight binding, but slow inhibitor of FXa, the TFPI/protein S system fails to regulate FXa generation at high tissue factor/FVIIa concentrations. In this review, we explain how TFPI/protein S can regain its activity at high tissue factor concentrations in the presence of APC, resulting in an intertwinement of TFPI- and APC-cofactor activities of protein S, and making TFPI a major determinant of APC-anticoagulant activity in plasma.
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