ArticleJournal of thrombosis and haemostasis : JTH2020
A mathematical model of coagulation under flow identifies factor V as a modifier of thrombin generation in hemophilia A.
Article in Journal of thrombosis and haemostasis : JTH, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Mathematical modeling of flow-mediated thrombin generation after treatment of postoperative bleeding in cardiac surgery with cardiopulmonary bypass.Journal of thrombosis and haemostasis : JTH · 2026Article
- Modeling the role of platelet-released polyphosphates in tissue factor-initiated coagulation under flow.Research and practice in thrombosis and haemostasis · 2026Article
- Mechanisms of thrombin inhibition by protein S and the TFPIα-fVshort-protein S complex.Biophysical journal · 2026Article
- Determination of Patient-Specific Blood Coagulation Kinetic Parameters via Neural Networks: Toward Thrombosis Prediction in Personalized Medicine.Annals of biomedical engineering · 2025Article
- Biophysical perspectives of the spatiotemporal dynamics of plasma coagulation under flow.Biophysical reviews · 2025Review
- Examining downstream effects of concizumab in hemophilia A with a mathematical modeling approach.Journal of thrombosis and haemostasis : JTH · 2025Article
- A new look at TFPI inhibition of factor X activation.PLoS computational biology · 2024Article
- Mathematical modeling identifies clotting factor combinations that modify thrombin generation in normal and factor VIII-, IX-, or XI-deficient blood.Research and practice in thrombosis and haemostasis · 2024Article
- Characterizing thrombus adhesion strength on common cardiovascular device materials.Frontiers in bioengineering and biotechnology · 2024Article
- A model of fluid-structure and biochemical interactions for applications to subclinical leaflet thrombosis.International journal for numerical methods in biomedical engineering · 2023Article
- Inhibition of platelet-surface-bound proteins during coagulation under flow I: TFPI.Biophysical journal · 2023Article
- Critical evaluation of kinetic schemes for coagulation.PloS one · 2023Article
- von Willebrand factor unfolding mediates platelet deposition in a model of high-shear thrombosis.Biophysical journal · 2022Article
- Antithrombin-III mitigates thrombin-mediated endothelial cell contraction and sickle red blood cell adhesion in microscale flow.British journal of haematology · 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
- DEVELOPMENT OF FIBRIN BRANCH STRUCTURE BEFORE AND AFTER GELATION.SIAM journal on applied mathematics · 2022Article
- Refining a numerical model for device-induced thrombosis and investigating the effects of non-Newtonian blood models.Journal of biomechanics · 2021Article
- Thrombin-Fibrinogen In Vitro Flow Model of Thrombus Growth in Cerebral Aneurysms.TH open : companion journal to thrombosis and haemostasis · 2021Article
- The Art and Science of Building a Computational Model to Understand Hemostasis.Seminars in thrombosis and hemostasis · 2021Review
- Computationally Driven Discovery in Coagulation.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe variability in bleeding patterns among individuals with hemophilia A, who have similar factor VIII (FVIII) levels, is significant and the origins are unknown.
objectiveTo use a previously validated mathematical model of flow-mediated coagulation as a screening tool to identify parameters that are most likely to enhance thrombin generation in the context of FVIII deficiency.
methodsWe performed a global sensitivity analysis (GSA) on our mathematical model to identify potential modifiers of thrombin generation. Candidates from the GSA were confirmed by calibrated automated thrombography (CAT) and flow assays on collagen-tissue factor (TF) surfaces at a shear rate of 100 per second.
resultsSimulations identified low-normal factor V (FV) (50%) as the strongest modifier, with additional thrombin enhancement when combined with high-normal prothrombin (150%). Low-normal FV levels or partial FV inhibition (60% activity) augmented thrombin generation in FVIII-inhibited or FVIII-deficient plasma in CAT. Partial FV inhibition (60%) boosted fibrin deposition in flow assays performed with whole blood from individuals with mild and moderate FVIII deficiencies. These effects were amplified by high-normal prothrombin levels in both experimental models.
conclusionsThese results show that low-normal FV levels can enhance thrombin generation in hemophilia A. Further explorations with the mathematical model suggest a potential mechanism: lowering FV reduces competition between FV and FVIII for factor Xa (FXa) on activated platelet surfaces (APS), which enhances FVIII activation and rescues thrombin generation in FVIII-deficient blood.
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