ArticleJournal of thrombosis and haemostasis : JTH2022
Revised model of the tissue factor pathway of thrombin generation: Role of the feedback activation of FXI.
Article in Journal of thrombosis and haemostasis : JTH, 2022. 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, 28 citations in OpenAlex.
- Factor XI Inhibition for the Prevention of Catheter-Associated Thrombosis in Patients With Cancer Undergoing Central Line Placement: A Phase 2 Clinical Trial.Arteriosclerosis, thrombosis, and vascular biology · 2024Trial
- Thrombin kinetics determines robust plasma clot architecture.Research and practice in thrombosis and haemostasis · 2026Article
- Regulated cell death-induced coagulation dysfunction in sepsis.Journal of thrombosis and thrombolysis · 2026Review
- Factor XII in Thrombosis and Thromboinflammation: From Molecular Biology to Clinical Translation.International journal of molecular sciences · 2026Review
- The hidden battlefield: platelet function in the wake of severe trauma.Frontiers in immunology · 2026Review
- Tapping Into the Natural PZ-Independent Anticoagulant Function of ZPI to Inhibit Thrombosis With Minimal Effect on Hemostasis.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- A Novel Human Anti-FV mAb as a Potential Tool for Diagnostic and Coagulation Inhibitory Approaches.International journal of molecular sciences · 2025Article
- A new look at TFPI inhibition of factor X activation.PLoS computational biology · 2024Article
- Biology of factor XI.Blood · 2024Review
- Selective factor XI/XIa inhibitors: a beacon of hope in anticoagulation therapy.Future medicinal chemistry · 2024Article
- Antithrombin Deficiency Is Associated with Prothrombotic Plasma Fibrin Clot Phenotype.Thrombosis and haemostasis · 2023Article
- A novel mouse whole blood thrombin generation assay sensitive to FXI- and FIX-mediated amplification of coagulation.Blood advances · 2023Article
- A Review of Quantitative Systems Pharmacology Models of the Coagulation Cascade: Opportunities for Improved Usability.Pharmaceutics · 2023Review
- Tissue factor pathway inhibitor is a potential modifier of bleeding risk in factor XI deficiency.Journal of thrombosis and haemostasis : JTH · 2023Article
- Complement component C1q initiates extrinsic coagulation via the receptor for the globular head of C1q in adventitial fibroblasts and vascular smooth muscle cells.Immunity, inflammation and disease · 2023Article
- Critical evaluation of kinetic schemes for coagulation.PloS one · 2023Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundBiochemical reaction networks are self-regulated in part due to feedback activation mechanisms. The tissue factor (TF) pathway of blood coagulation is a complex reaction network controlled by multiple feedback loops that coalesce around the serine protease thrombin.
objectivesOur goal was to evaluate the relative contribution of the feedback activation of coagulation factor XI (FXI) in TF-mediated thrombin generation using a comprehensive systems-based analysis. MATERIALS AND
methodsWe developed a systems biology model that improves the existing Hockin-Mann (HM) model through an integrative approach of mathematical modeling and in vitro experiments. Thrombin generation measured using in vitro assays revealed that the feedback activation of FXI contributes to the propagation of thrombin generation based on the initial concentrations of TF or activated coagulation factor X (FXa). We utilized experimental data to improve the robustness of the HM model to capture thrombin generation kinetics without a role for FXI before including the feedback activation of FXI by thrombin to construct the extended (ext.) HM model. RESULTS AND
conclusionsUsing the ext.HM model, we predicted that the contribution of positive feedback of FXI activation by thrombin can be abolished by selectively eliminating the inhibitory function of tissue factor pathway inhibitor (TFPI), a serine protease inhibitor of FXa and TF-activated factor VII (FVIIa) complex. This prediction from the ext.HM model was experimentally validated using thrombin generation assays with function blocking antibodies against TFPI and plasmas depleted of FXI. Together, our results demonstrate the applications of combining experimental and modeling techniques in predicting complex biochemical reaction systems.
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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.