ArticleThrombosis and haemostasis2018
Suppressive Role of Tissue Factor Pathway Inhibitor-α in Platelet-Dependent Fibrin Formation under Flow Is Restricted to Low Procoagulant Strength.
Article in Thrombosis and haemostasis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Association of TFPI polymorphisms rs8176592, rs10931292, and rs10153820 with venous thrombosis: A meta-analysis.Medicine · 2019Pooled it
- Concizumab improves clot formation in hemophilia A under flow.Journal of thrombosis and haemostasis : JTH · 2024Article
- Inhibition of platelet-surface-bound proteins during coagulation under flow I: TFPI.Biophysical journal · 2023Article
- Inhibition of platelet adhesion, thrombus formation, and fibrin formation by a potent αIIbβ3 integrin inhibitor from ticks.Research and practice in thrombosis and haemostasis · 2021Article
- Platelet anticoagulant proteins: Modulators of thrombosis propensity within a procoagulant cell.Journal of thrombosis and haemostasis : JTH · 2020Article
- Platelet-primed interactions of coagulation and anticoagulation pathways in flow-dependent thrombus formation.Scientific reports · 2020Article
- Localized endothelial-based control of platelet aggregation and coagulation under flow: A proof-of-principle vessel-on-a-chip study.Journal of thrombosis and haemostasis : JTH · 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
- Microfluidic hemophilia models using blood from healthy donors.Research and practice in thrombosis and haemostasis · 2020Article
- Article
- Integrating platelet and coagulation activation in fibrin clot formation.Research and practice in thrombosis and haemostasis · 2018Review
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Tissue factor pathway inhibitor-alpha (TFPI-α) is a Kunitz-type serine protease inhibitor, which suppresses coagulation by inhibiting the tissue factor (TF)/factor VIIa complex as well as factor Xa. In static plasma-phospholipid systems, TFPI-α thus suppresses both factor Xa and thrombin generation. In this article, we used a microfluidics approach to investigate how TFPI-α regulates fibrin clot formation in platelet thrombi at low wall shear rate. We therefore hypothesized that the anticoagulant effect of TFPI-α in plasma is a function of the local procoagulant strength-defined as the magnitude of thrombin generation under flow, due to local activities of TF/factor VIIa and factor Xa. To test this hypothesis, we modulated local coagulation by microspot coating of flow channels with 0 to 100 pM TF/collagen, or by using blood from patients with haemophilia A or B. For blood or plasma from healthy subjects, blocking of TFPI-α enhanced fibrin formation, extending from a platelet thrombus, under flow only at <2 pM coated TF. This enhancement was paralleled by an increased thrombin generation. For mouse plasma, genetic deficiency in TFPI enhanced fibrin formation under flow also at 0 pM TF microspots. On the other hand, using blood from haemophilia A or B patients, TFPI-α antagonism markedly enhanced fibrin formation at microspots with up to 100 pM coated TF. We conclude that, under flow, TFPI-α is capable to antagonize fibrin formation in a manner dependent on and restricted by local TF/factor VIIa and factor Xa activities.
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