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Navarro S, Stegner D, Nieswandt B, et al. Temporal Roles of Platelet and Coagulation Pathways in Collagen- and Tissue Factor-Induced Thrombus Formation. Int J Mol Sci. 2021;23(1)doi: 10.3390/ijms23010358.
Navarro, S., Stegner, D., Nieswandt, B., Heemskerk, J. W. M., & Kuijpers, M. J. E. (2021). Temporal Roles of Platelet and Coagulation Pathways in Collagen- and Tissue Factor-Induced Thrombus Formation. International journal of molecular sciences, 23(1), . https://doi.org/10.3390/ijms23010358
Navarro, Stefano, et al. "Temporal Roles of Platelet and Coagulation Pathways in Collagen- and Tissue Factor-Induced Thrombus Formation." International journal of molecular sciences vol. 23,1 (2021). doi: https://doi.org/10.3390/ijms23010358
Navarro S, Stegner D, Nieswandt B, Heemskerk JWM, Kuijpers MJE. Temporal Roles of Platelet and Coagulation Pathways in Collagen- and Tissue Factor-Induced Thrombus Formation. Int J Mol Sci. 2021 Dec 29;23(1). doi: 10.3390/ijms23010358. PMID: 35008781.
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Int J Mol Sci. 2021 Dec 29;23(1). doi: 10.3390/ijms23010358.

Temporal Roles of Platelet and Coagulation Pathways in Collagen- and Tissue Factor-Induced Thrombus Formation.

International journal of molecular sciences

Stefano Navarro, David Stegner, Bernhard Nieswandt, Johan W M Heemskerk, Marijke J E Kuijpers

Affiliations

  1. Institute of Experimental Biomedicine I, University Hospital Würzburg, Würzburg Josef-Schneider-Straße 2, 97080 Wurzburg, Germany.
  2. Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, 97080 Wurzburg, Germany.
  3. Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The Netherlands.
  4. Synapse Research Institute, Kon. Emmaplein 7, 6214 KD Maastricht, The Netherlands.
  5. Thrombosis Expertise Center, Heart and Vascular Center, Maastricht University Medical Center+, Maastricht, Professor Debyelaan 25, 6229 HX Maastricht, The Netherlands.

PMID: 35008781 DOI: 10.3390/ijms23010358

Abstract

In hemostasis and thrombosis, the complex process of thrombus formation involves different molecular pathways of platelet and coagulation activation. These pathways are considered as operating together at the same time, but this has not been investigated. The objective of our study was to elucidate the time-dependency of key pathways of thrombus and clot formation, initiated by collagen and tissue factor surfaces, where coagulation is triggered via the extrinsic route. Therefore, we adapted a microfluidics whole-blood assay with the Maastricht flow chamber to acutely block molecular pathways by pharmacological intervention at desired time points. Application of the technique revealed crucial roles of glycoprotein VI (GPVI)-induced platelet signaling via Syk kinase as well as factor VIIa-induced thrombin generation, which were confined to the first minutes of thrombus buildup. A novel anti-GPVI Fab EMF-1 was used for this purpose. In addition, platelet activation with the protease-activating receptors 1/4 (PAR1/4) and integrin αIIbβ3 appeared to be prolongedly active and extended to later stages of thrombus and clot formation. This work thereby revealed a more persistent contribution of thrombin receptor-induced platelet activation than of collagen receptor-induced platelet activation to the thrombotic process.

Keywords: coagulation; fibrin; glycoprotein VI; platelet receptors; spatiotemporal thrombus; thrombin

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