ArticleBlood2015
A balance between TFPI and thrombin-mediated platelet activation is required for murine embryonic development.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Intercellular synergy between protease-activated receptors 1 and 4 during mouse development.Journal of thrombosis and haemostasis : JTH · 2025Article
- Comparative Thrombin Generation in Animal Plasma: Sensitivity to Human Factor XIa and Tissue Factor.International journal of molecular sciences · 2023Article
- Platelet tissue factor pathway inhibitor-α dampens cardiac thrombosis and associated fibrosis in mice.Journal of thrombosis and haemostasis : JTH · 2023Article
- Novel venous thromboembolism mouse model to evaluate the role of complete and partial factor XIII deficiency in pulmonary embolism risk.Journal of thrombosis and haemostasis : JTH · 2021Article
- The contribution of TFPIα to the hemostatic response to injury in mice.Journal of thrombosis and haemostasis : JTH · 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
- Defective fibrin deposition and thrombus stability in BambiJournal of thrombosis and haemostasis : JTH · 2019Article
- Factors Associated with Low Admission Platelet Count in Adults with Acute Aortic Dissection.Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia · 2019Article
- Maintaining extraembryonic expression allows generation of mice with severe tissue factor pathway inhibitor deficiency.Blood advances · 2019Article
- Advances and innovations in haemophilia treatment.Nature reviews. Drug discovery · 2018Review
- 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
- Correlates of plasma and platelet tissue factor pathway inhibitor, factor V, and Protein S.Research and practice in thrombosis and haemostasis · 2018Article
- Generation of α-1,3-galactosyltransferase knocked-out transgenic cloned pigs with knocked-in five human genes.Transgenic research · 2017Article
- A combined deficiency of tissue factor and PAR-4 is associated with fatal pulmonary hemorrhage in mice.Thrombosis research · 2016Article
- Targeting TFPI for hemophilia treatment.Thrombosis research · 2016Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Tissue factor pathway inhibitor (TFPI) is a critical anticoagulant protein present in endothelium and platelets. Mice lacking TFPI (Tfpi(-/-)) die in utero from disseminated intravascular coagulation. They are rescued by concomitant tissue factor (TF) deficiency, demonstrating that TFPI modulates TF function in vivo. Recent studies have found TFPI inhibits prothrombinase activity during the initiation of coagulation and limits platelet accumulation during thrombus formation, implicating TFPI in modulating platelet procoagulant activity. To examine whether altered platelet function would compensate for the lack of TFPI and rescue TFPI-null embryonic lethality, Tfpi(+/-) mice lacking the platelet thrombin receptor, protease activated receptor 4 (PAR4; Par4(-/-)), or its coreceptor, PAR3, were mated. PAR3 deficiency did not rescue Tfpi(-/-) embryos, but >40% of expected Tfpi(-/-):Par4(-/-) offspring survived to adulthood. Adult Tfpi(-/-):Par4(-/-) mice did not exhibit overt thrombosis. However, they had focal sterile inflammation with fibrin(ogen) deposition in the liver and elevated plasma thrombin-antithrombin complexes, indicating activation of coagulation at baseline. Tfpi(-/-):Par4(-/-) mice have platelet and fibrin accumulation similar to Par4(-/-) mice following venous electrolytic injury but were more susceptible than Par4(-/-) mice to TF-induced pulmonary embolism. In addition, ∼30% of the Tfpi(-/-):Par4(-/-) mice were born with short tails. Tfpi(-/-):Par4(-/-) mice are the first adult mice described that lack TFPI with unaltered TF. They demonstrate that TFPI physiologically modulates thrombin-dependent platelet activation in a manner that is required for successful embryonic development and identify a role for TFPI in dampening intravascular procoagulant stimuli that lead to thrombin generation, even in the absence of thrombin-mediated platelet activation.
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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.