ArticlePLoS computational biology2019
Reduced model to predict thrombin and fibrin during thrombosis on collagen/tissue factor under venous flow: Roles of γ'-fibrin and factor XIa.
Article in PLoS computational biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Mesoscale Simulations of Blood Coagulation in Flow and Quiescent Domains Using SDPD.International journal for numerical methods in biomedical engineering · 2026Article
- Article
- Multiscale simulations that incorporate patient-specific neural network models of platelet calcium signaling predict diverse thrombotic outcomes under flow.PLoS computational biology · 2025Article
- Analysis of fibrin networks using topological data analysis - a feasibility study.Scientific reports · 2024Article
- Investigating thrombin-loaded fibrin in whole blood clot microfluidic assay via fluorogenic peptide.Biophysical journal · 2023Article
- Critical evaluation of kinetic schemes for coagulation.PloS one · 2023Article
- A fibrin enhanced thrombosis model for medical devices operating at low shear regimes or large surface areas.PLoS computational biology · 2022Article
- Mathematical modeling to understand the role of bivalent thrombin-fibrin binding during polymerization.PLoS computational biology · 2022Article
- Revised model of the tissue factor pathway of thrombin generation: Role of the feedback activation of FXI.Journal of thrombosis and haemostasis : JTH · 2022Article
- Computational Biomechanical Modeling of Fibrin Networks and Platelet-Fiber Network Interactions.Current opinion in biomedical engineering · 2022Article
- Multiphysics and multiscale modeling of microthrombosis in COVID-19.PLoS computational biology · 2022Article
- Semi-automated thrombin dynamics applying the ST Genesia thrombin generation assay.Frontiers in cardiovascular medicine · 2022Article
- A three-dimensional multiscale model for the prediction of thrombus growth under flow with single-platelet resolution.PLoS computational biology · 2022Article
- Thrombosis and Hemodynamics: external and intrathrombus gradients.Current opinion in biomedical engineering · 2021Article
- Thrombin-Fibrinogen In Vitro Flow Model of Thrombus Growth in Cerebral Aneurysms.TH open : companion journal to thrombosis and haemostasis · 2021Article
- Thermal shift assay to probe melting of thrombin, fibrinogen, fibrin monomer, and fibrin: Gly-Pro-Arg-Pro induces a fibrin monomer-like state in fibrinogen.Biochimica et biophysica acta. General subjects · 2021Article
- Sensitivity analysis of a reduced model of thrombosis under flow: Roles of Factor IX, Factor XI, and γ'-Fibrin.PloS one · 2021Article
- Article
- Modeling Thrombin Generation in Plasma under Diffusion and Flow.Biophysical journal · 2020Article
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2 authors at 1 institution in 1 country.
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Abstract
During thrombosis, thrombin generates fibrin, however fibrin reversibly binds thrombin with low affinity E-domain sites (KD = 2.8 μM) and high affinity γ'-fibrin sites (KD = 0.1 μM). For blood clotting on collagen/tissue factor (1 TF-molecule/μm2) at 200 s-1 wall shear rate, high μM-levels of intraclot thrombin suggest robust prothrombin penetration into clots. Setting intraclot zymogen concentrations to plasma levels (and neglecting cofactor rate limitations) allowed the linearization of 7 Michaelis-Menton reactions between 6 species to simulate intraclot generation of: Factors FXa (via TF/VIIa or FIXa), FIXa (via TF/FVIIa or FXIa), thrombin, fibrin, and FXIa. This reduced model [7 rates, 2 KD's, enzyme half-lives~1 min] predicted the measured clot elution rate of thrombin-antithrombin (TAT) and fragment F1.2 in the presence and absence of the fibrin inhibitor Gly-Pro-Arg-Pro. To predict intraclot fibrin reaching 30 mg/mL by 15 min, the model required fibrinogen penetration into the clot to be strongly diffusion-limited (actual rate/ideal rate = 0.05). The model required free thrombin in the clot (~100 nM) to have an elution half-life of ~2 sec, consistent with measured albumin elution, with most thrombin (>99%) being fibrin-bound. Thrombin-feedback activation of FXIa became prominent and reached 5 pM FXIa at >500 sec in the simulation, consistent with anti-FXIa experiments. In predicting intrathrombus thrombin and fibrin during 15-min microfluidic experiments, the model revealed "cascade amplification" from 30 pM levels of intrinsic tenase to 15 nM prothrombinase to 15 μM thrombin to 90 μM fibrin. Especially useful for multiscale simulation, this reduced model predicts thrombin and fibrin co-regulation during thrombosis under flow.
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