ArticleProceedings of the National Academy of Sciences of the United States of America2013
Tissue factor pathway inhibitor-alpha inhibits prothrombinase during the initiation of blood coagulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.
- Single nucleotide polymorphisms in an intergenic chromosome 2q region associated with tissue factor pathway inhibitor plasma levels and venous thromboembolism.Journal of thrombosis and haemostasis : JTH · 2016Pooled it
- Befovacimab, an anti-tissue factor pathway inhibitor antibody: Early termination of the multiple-dose, dose-escalating Phase 2 study due to thrombosis.Haemophilia : the official journal of the World Federation of Hemophilia · 2022Trial
- Thrombin generation abnormalities in Quebec platelet disorder.International journal of laboratory hematology · 2020Trial
- Challenges in the Quantification of Free TFPI in Human Plasma Following Marstacimab Treatment.The AAPS journal · 2026Article
- Thrombotic and ischemic event reporting with anticoagulant reversal agents: a multi-agent FAERS pharmacovigilance study.Journal of thrombosis and thrombolysis · 2026Article
- 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
- Elevated tissue factor pathway inhibitor delays thrombin generation in COVID-19 but is not associated with clinical outcomes.Blood vessels, thrombosis & hemostasis · 2025Article
- Basic regions of factor V and tissue factor pathway inhibitor mediate heavy chain and acidic region interactions on factor V revealed by tethered chemical cleavage.Journal of thrombosis and haemostasis : JTH · 2025Article
- Placental Vascular Defects and Embryonic Lethality Triggered by TFPIα Deficiency in Factor V Leiden Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Examining downstream effects of concizumab in hemophilia A with a mathematical modeling approach.Journal of thrombosis and haemostasis : JTH · 2025Article
- The common VTE-protective G haplotype of F5 increases factor V-short, TFPI function, and risk of bleeding.Blood advances · 2025Article
- Peripheral artery disease and local drug delivery: a review of disease pathology and drug delivery systems for therapy below the knee.Experimental biology and medicine (Maywood, N.J.) · 2025Review
- Mathematical modeling identifies clotting factor combinations that modify thrombin generation in normal and factor VIII-, IX-, or XI-deficient blood.Research and practice in thrombosis and haemostasis · 2024Article
- Concizumab improves clot formation in hemophilia A under flow.Journal of thrombosis and haemostasis : JTH · 2024Article
- Genetic factors, risk prediction and AI application of thrombotic diseases.Experimental hematology & oncology · 2024Review
- Mutational analysis of pig tissue factor pathway inhibitor α to increase anti-coagulation activity in pig-to-human xenotransplantation.Biotechnology letters · 2024Article
- Structural architecture of the acidic region of the B domain of coagulation factor V.Journal of thrombosis and haemostasis : JTH · 2024Article
- TFPIα anticoagulant function is highly dependent on protein S in vivo.Science advances · 2024Article
- Factor V variants in bleeding and thrombosis.Research and practice in thrombosis and haemostasis · 2024Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
Abstract
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 region of the B domain. We demonstrate rapid inhibition of prothrombinase by TFPIα mediated through a high-affinity exosite interaction between the basic region of TFPIα and the FV acidic region, which is retained in FXa-activated FVa and platelet FVa. This inhibitory activity is not mediated by TFPIβ and is lost upon removal of the acidic region of FVa by thrombin. The data identify a previously undescribed, isoform-specific anticoagulant function for TFPIα and are a unique description of physiologically relevant inhibition of prothrombinase. These findings, combined with previous descriptions of differential expression patterns of TFPIα and TFPIβ in platelets and endothelial cells, suggest that the TFPI isoforms may act through distinct mechanisms to inhibit the initial stages of intravascular coagulation, with TFPIβ acting to dampen TF expressed on the surface of vascular cells, whereas TFPIα dampens the initial prothrombinase formed on the activated platelet surface.
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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.