ArticleBlood2017
Selective factor VIII activation by the tissue factor-factor VIIa-factor Xa complex.
Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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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.
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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
38 citing papers in PubMed, 74 citations in OpenAlex.
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- Kenaf Seed Cysteine Protease (KSCP) Inhibits the Intrinsic Pathway of the Blood Coagulation Cascade and Platelet Aggregation.Current protein & peptide science · 2024Article
- The Role of the Complement System in the Pathogenesis of Infectious Forms of Hemolytic Uremic Syndrome.Biomolecules · 2023Review
- Serum Reactive Antibodies against the N-Methyl-D-Aspartate Receptor NR2 Subunit-Could They Act as Potential Biomarkers?International journal of molecular sciences · 2023Article
- Tumor-expressed factor VII is associated with survival and regulates tumor progression in breast cancer.Blood advances · 2023Article
- Development of Personalized Thrombogenesis and Thrombin Generation Assays to Assess Endothelial Dysfunction in Cardiovascular Diseases.Biomedicines · 2023Article
- A novel mouse whole blood thrombin generation assay sensitive to FXI- and FIX-mediated amplification of coagulation.Blood advances · 2023Article
- Differences in wild-type- and R338L-tenase complex formation are at the root of R338L-factor IX assay discrepancies.Blood advances · 2023Article
- Coagulation signaling from amniotic fluid to fetal skin.Blood advances · 2022Article
- EPCR-PAR1 biased signaling regulates perfusion recovery and neovascularization in peripheral ischemia.JCI insight · 2022Article
- Regulation of coagulation by tissue factor pathway inhibitor: Implications for hemophilia therapy.Journal of thrombosis and haemostasis : JTH · 2022Review
- FVIII regulates the molecular profile of endothelial cells: functional impact on the blood barrier and macrophage behavior.Cellular and molecular life sciences : CMLS · 2022Article
- Anticoagulant SERPINs: Endogenous Regulators of Hemostasis and Thrombosis.Frontiers in cardiovascular medicine · 2022Review
- Coagulation and complement: Key innate defense participants in a seamless web.Frontiers in immunology · 2022Review
- Article
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
Safe and effective antithrombotic therapy requires understanding of mechanisms that contribute to pathological thrombosis but have a lesser impact on hemostasis. We found that the extrinsic tissue factor (TF) coagulation initiation complex can selectively activate the antihemophilic cofactor, FVIII, triggering the hemostatic intrinsic coagulation pathway independently of thrombin feedback loops. In a mouse model with a relatively mild thrombogenic lesion, TF-dependent FVIII activation sets the threshold for thrombus formation through contact phase-generated FIXa. In vitro, FXa stably associated with TF-FVIIa activates FVIII, but not FV. Moreover, nascent FXa product of TF-FVIIa can transiently escape the slow kinetics of Kunitz-type inhibition by TF pathway inhibitor and preferentially activates FVIII over FV. Thus, TF synergistically primes FIXa-dependent thrombin generation independently of cofactor activation by thrombin. Accordingly, FVIIa mutants deficient in direct TF-dependent thrombin generation, but preserving FVIIIa generation by nascent FXa, can support intrinsic pathway coagulation. In ex vivo flowing blood, a TF-FVIIa mutant complex with impaired free FXa generation but activating both FVIII and FIX supports efficient FVIII-dependent thrombus formation. Thus, a previously unrecognized TF-initiated pathway directly yielding FVIIIa-FIXa intrinsic tenase complex may be prohemostatic before further coagulation amplification by thrombin-dependent feedback loops enhances the risk of thrombosis.
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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.