ArticleBlood2015
FXIa and platelet polyphosphate as therapeutic targets during human blood clotting on collagen/tissue factor surfaces under flow.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
- Modeling the role of platelet-released polyphosphates in tissue factor-initiated coagulation under flow.Research and practice in thrombosis and haemostasis · 2026Article
- Fluorescent peptide for detecting factor XIIIa activity and fibrin in whole blood clots forming under flow.Research and practice in thrombosis and haemostasis · 2024Article
- Smart thrombosis inhibitors without bleeding side effects via charge tunable ligand design.Nature communications · 2023Article
- Advances in Enhancing Hemocompatibility of Hemodialysis Hollow-Fiber Membranes.Advanced fiber materials · 2023Review
- Activation of Most Toll-Like Receptors in Whole Human Blood Attenuates Platelet Deposition on Collagen under Flow.Journal of immunology research · 2023Article
- ADP and Thromboxane Inhibitors Both Reduce Global Contraction of Clot Length, While Thromboxane Inhibition Attenuates Internal Aggregate Contraction.TH open : companion journal to thrombosis and haemostasis · 2022Article
- Point of care whole blood microfluidics for detecting and managing thrombotic and bleeding risks.Lab on a chip · 2021Review
- Computational modeling of blood component transport related to coronary artery thrombosis in Kawasaki disease.PLoS computational biology · 2021Article
- Pharmacological Activities and Mechanisms of Hirudin and Its Derivatives - A Review.Frontiers in pharmacology · 2021Review
- Sensitivity analysis of a reduced model of thrombosis under flow: Roles of Factor IX, Factor XI, and γ'-Fibrin.PloS one · 2021Article
- Core and shell platelets of a thrombus: A new microfluidic assay to study mechanics and biochemistry.Research and practice in thrombosis and haemostasis · 2020Article
- Scalable manufacture of a disposable, storage-stable eight-channel microfluidic device for rapid testing of platelet, coagulation, and drug function under whole blood flow.Biomicrofluidics · 2020Article
- Src family kinases inhibition by dasatinib blocks initial and subsequent platelet deposition on collagen under flow, but lacks efficacy with thrombin generation.Thrombosis research · 2020Article
- A mathematical model of coagulation under flow identifies factor V as a modifier of thrombin generation in hemophilia A.Journal of thrombosis and haemostasis : JTH · 2020Article
- Differential roles of factors IX and XI in murine placenta and hemostasis under conditions of low tissue factor.Blood advances · 2020Article
- Microfluidic hemophilia models using blood from healthy donors.Research and practice in thrombosis and haemostasis · 2020Article
- Microfluidic and computational study of structural properties and resistance to flow of blood clots under arterial shear.Biomechanics and modeling in mechanobiology · 2019Article
- Reduced model to predict thrombin and fibrin during thrombosis on collagen/tissue factor under venous flow: Roles of γ'-fibrin and factor XIa.PLoS computational biology · 2019Article
- Impact of Deficiency of Intrinsic Coagulation Factors XI and XII on Ex Vivo Thrombus Formation and Clot Lysis.TH open : companion journal to thrombosis and haemostasis · 2019Article
- Polyphosphate in thrombosis, hemostasis, and inflammation.Research and practice in thrombosis and haemostasis · 2019Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Factor XIIa (FXIIa) and factor XIa (FXIa) contribute to thrombosis in animal models, whereas platelet-derived polyphosphate (polyP) may potentiate contact or thrombin-feedback pathways. The significance of these mediators in human blood under thrombotic flow conditions on tissue factor (TF) -bearing surfaces remains inadequately resolved. Human blood (corn trypsin inhibitor treated [4 μg/mL]) was tested by microfluidic assay for clotting on collagen/TF at TF surface concentration ([TF]wall) from ∼0.1 to 2 molecules per μm(2). Anti-FXI antibodies (14E11 and O1A6) or polyP-binding protein (PPXbd) were used to block FXIIa-dependent FXI activation, FXIa-dependent factor IX (FIX) activation, or platelet-derived polyP, respectively. Fibrin formation was sensitive to 14E11 at 0 to 0.1 molecules per µm(2) and sensitive to O1A6 at 0 to 0.2 molecules per µm(2). However, neither antibody reduced fibrin generation at ∼2 molecules per µm(2) when the extrinsic pathway became dominant. Interestingly, PPXbd reduced fibrin generation at low [TF]wall (0.1 molecules per µm(2)) but not at zero or high [TF]wall, suggesting a role for polyP distinct from FXIIa activation and requiring low extrinsic pathway participation. Regardless of [TF]wall, PPXbd enhanced fibrin sensitivity to tissue plasminogen activator and promoted clot retraction during fibrinolysis concomitant with an observed PPXbd-mediated reduction of fibrin fiber diameter. This is the first detection of endogenous polyP function in human blood under thrombotic flow conditions. When triggered by low [TF]wall, thrombosis may be druggable by contact pathway inhibition, although thrombolytic susceptibility may benefit from polyP antagonism regardless of [TF]wall.
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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.