TFPI-dependent activities of Protein S

Sameera Peraramelli, Jan Rosing, Tilman M. Hackeng*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)S23-S26
JournalThrombosis Research
Publication statusPublished - May 2012


  • TFPI
  • protein S
  • APC
  • anticoagulants

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