ArticleArteriosclerosis, thrombosis, and vascular biology2014
Protein S is a cofactor for platelet and endothelial tissue factor pathway inhibitor-α but not for cell surface-associated tissue factor pathway inhibitor.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 53 citations in OpenAlex.
- Protein S: a vitamin K-dependent factor bridging haemostasis, tissue homeostasis and cancer.The Biochemical journal · 2026Review
- TFPIα inhibition by andexanet alfa is partially restored by protein S and factor V-short.Blood advances · 2026Article
- Mechanisms of thrombin inhibition by protein S and the TFPIα-fVshort-protein S complex.Biophysical journal · 2026Article
- Unfolded von Willebrand factor binds protein S and reduces anticoagulant activity.Blood vessels, thrombosis & hemostasis · 2025Article
- Examining downstream effects of concizumab in hemophilia A with a mathematical modeling approach.Journal of thrombosis and haemostasis : JTH · 2025Article
- Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications.Cell communication and signaling : CCS · 2024Review
- TFPIα anticoagulant function is highly dependent on protein S in vivo.Science advances · 2024Article
- Protein S antibody as an adjunct therapy for hemophilia B.Blood advances · 2024Article
- Activated protein C, protein S, and tissue factor pathway inhibitor cooperate to inhibit thrombin activation.Thrombosis research · 2023Article
- Cryo-EM structure of coagulation factor V short.Blood · 2023Article
- Dysregulation of Protein S in COVID-19.Best practice & research. Clinical haematology · 2022Review
- Regulation of coagulation by tissue factor pathway inhibitor: Implications for hemophilia therapy.Journal of thrombosis and haemostasis : JTH · 2022Review
- Laminin G1 residues of protein S mediate its TFPI cofactor function and are competitively regulated by C4BP.Blood advances · 2022Article
- Anti-tissue factor pathway inhibitor (TFPI) therapy: a novel approach to the treatment of haemophilia.International journal of hematology · 2020Review
- Re-evaluation of mouse tissue factor pathway inhibitor and comparison of mouse and human tissue factor pathway inhibitor physiology.Journal of thrombosis and haemostasis : JTH · 2018Article
- Advances in Clinical and Basic Science of Coagulation: Illustrated abstracts of the 9th Chapel Hill Symposium on Hemostasis.Research and practice in thrombosis and haemostasis · 2018Review
- Review
- Suppressive Role of Tissue Factor Pathway Inhibitor-α in Platelet-Dependent Fibrin Formation under Flow Is Restricted to Low Procoagulant Strength.Thrombosis and haemostasis · 2018Article
- Elevated Plasma Factor IXa Activity in Premenopausal Women on Hormonal Contraception.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Platelet full length TFPI-α in healthy volunteers is not affected by sex or hormonal use.PloS one · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTissue factor pathway inhibitor (TFPI) is produced in 2 isoforms: TFPIα, a soluble protein in plasma, platelets, and endothelial cells, and TFPIβ, a glycosylphosphatidylinositol-anchored protein on endothelium. Protein S (PS) functions as a cofactor for TFPIα, enhancing the inhibition of factor Xa. However, PS does not alter the inhibition of prothrombinase by TFPIα, and PS interactions with TFPIβ are undescribed. Thus, the physiological role and scope of the PS-TFPI system remain unclear. APPROACH AND
resultsHere, the cofactor activity of PS toward platelet and endothelial TFPIα and endothelial TFPIβ was quantified. PS enhanced the inhibition of factor Xa by TFPIα from platelets and endothelial cells and stabilized the TFPIα/factor Xa inhibitory complex, delaying thrombin generation by prothrombinase. By contrast, PS did not enhance the inhibitory activity of TFPIβ or a membrane-anchored form of TFPI containing the PS-binding third Kunitz domain (K1K2K3) although PS did function as a cofactor for K1K2K3 enzymatically released from the cell surface.
conclusionsThe PS-TFPI anticoagulant system is limited to plasma TFPIα and TFPIα released from platelets and endothelial cells. PS likely functions to localize solution-phase TFPIα to the cell surface, where factor Xa is bound. PS does not alter the activity of membrane-associated TFPI. Because activated platelets release TFPIα and PS, the PS-TFPIα anticoagulant system may act physiologically to dampen thrombin generation at the platelet surface.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.