Reduced prothrombinase inhibition by tissue factor pathway inhibitor contributes to the factor V Leiden hypercoagulable state

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Protein S stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor.

Tissue factor (TF) plays an important role in hemostasis, inflammation, angiogenesis, and the pathophysiology of atherosclerosis and cancer. In this article we uncover a mechanism in which protein S, which is well known as the cofactor of activated protein C, specifically inhibits TF activity by promoting the interaction between full-length TF pathway inhibitor (TFPI) and factor Xa (FXa). The s...

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Prothrombinase is protected from inactivation by tissue factor pathway inhibitor: competition between prothrombin and inhibitor.

The inhibition of prothrombinase by tissue factor pathway inhibitor (TFPI) has been studied in the presence and absence of prothrombin. The rate constant of association of prothrombinase with full-length TFPI was 2.1x10(7) M-1.s-1 and 0.05x10(7) M-1.s-1 for the reaction with C-terminus truncated TFPI (TFPI1-161). The rate constant of dissociation was 0.65x10(-4) s-1 in both cases. The rate cons...

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Tissue factor (TF) pathway inhibitor (TFPI) is a well-characterized activated factor X (FXa)-dependent inhibitor of TF-initiated coagulation produced in two alternatively spliced isoforms, TFPIα and TFPIβ. The TFPIα C terminus has a basic sequence nearly identical to a portion of the factor V (FV) B domain necessary for maintaining FV in an inactive conformation via interaction with an acidic r...

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ژورنال

عنوان ژورنال: Blood Advances

سال: 2017

ISSN: 2473-9529,2473-9537

DOI: 10.1182/bloodadvances.2016002295