ArticleBlood advances2017
TFPIα interacts with FVa and FXa to inhibit prothrombinase during the initiation of coagulation.
Article in Blood advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Measuring Neural Factor X Pathway Activity in Rodent Glioma Cell Culture and Brain Slices.Journal of molecular medicine (Berlin, Germany) · 2026Article
- 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
- 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
- Factor V variants in bleeding and thrombosis.Research and practice in thrombosis and haemostasis · 2024Article
- Post-transcriptional control of haemostatic genes: mechanisms and emerging therapeutic concepts in thrombo-inflammatory disorders.Cardiovascular research · 2023Review
- Tissue factor pathway inhibitor is a potential modifier of bleeding risk in factor XI deficiency.Journal of thrombosis and haemostasis : JTH · 2023Article
- Inhibition of platelet-surface-bound proteins during coagulation under flow I: TFPI.Biophysical journal · 2023Article
- Regulation of coagulation by tissue factor pathway inhibitor: Implications for hemophilia therapy.Journal of thrombosis and haemostasis : JTH · 2022Review
- A hydrophobic patch (PLVIVG; 1481-1486) in the B-domain of factor V-short is crucial for its synergistic TFPIα-cofactor activity with protein S and for the formation of the FXa-inhibitory complex comprising FV-short, TFPIα, and protein S.Journal of thrombosis and haemostasis : JTH · 2022Article
- Factor V east Texas variant causes bleeding in a three-generation family.Journal of thrombosis and haemostasis : JTH · 2022Article
- Intersection of regulatory pathways controlling hemostasis and hemochorial placentation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Changes of fibrinolytic system in thrombolytic resuscitation of pulmonary thromboembolism-induced cardiac arrest model.International wound journal · 2021Article
- The contribution of TFPIα to the hemostatic response to injury in mice.Journal of thrombosis and haemostasis : JTH · 2021Article
- CD248 enhances tissue factor procoagulant function, promoting arterial and venous thrombosis in mouse models.Journal of thrombosis and haemostasis : JTH · 2021Article
- Major Reservoir for Heparin-Releasable TFPIα (Tissue Factor Pathway Inhibitor α) Is Extracellular Matrix.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Intrauterine lethality in Tfpi gene disrupted mice is differentially suppressed during mid- and late-gestation by platelet TFPIα overexpression.Journal of thrombosis and haemostasis : JTH · 2021Article
- Article
- Risk factors, hematological and biochemical profile associated with colic in Delman horses in Gresik, Indonesia.F1000Research · 2021Article
- Platelet anticoagulant proteins: Modulators of thrombosis propensity within a procoagulant cell.Journal of thrombosis and haemostasis : JTH · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Tissue factor pathway inhibitor α (TFPIα) inhibits prothrombinase, the thrombin-generating complex of factor Xa (FXa) and factor Va (FVa), during the initiation of coagulation. This inhibition requires binding of a conserved basic region within TFPIα to a conserved acidic region in FXa-activated and platelet-released FVa. In this study, the contribution of interactions between TFPIα and the FXa active site and FVa heavy chain to prothrombinase inhibition were examined to further define the inhibitory biochemistry. Removal of FXa active site binding by mutation or by deletion of the second Kunitz domain (K2) of TFPIα produced 17- or 34-fold weaker prothrombinase inhibition, respectively, establishing that K2 binding to the FXa active site is required for efficient inhibition. Substitution of the TFPIα basic region uncharged residues (Leu252, Ile253, Thr255) with Ala (TFPI-AAKA) produced 5.8-fold decreased inhibition. This finding was confirmed using a basic region peptide (Leu252-Lys261) and Ala substitution peptides, which established that the uncharged residues are required for prothrombinase inhibitory activity but not for binding the FVa acidic region. This suggests that the uncharged residues mediate a secondary interaction with FVa subsequent to acidic region binding. This secondary interaction seems to be with the FVa heavy chain, because the FV Leiden mutation weakened prothrombinase inhibition by TFPIα but did not alter TFPI-AAKA inhibitory activity. Thus, efficient inhibition of prothrombinase by TFPIα requires at least 3 intermolecular interactions: (1) the TFPIα basic region binds the FVa acidic region, (2) K2 binds the FXa active site, and (3) Leu252-Thr255 binds the FVa heavy chain.
Identifiers
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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.