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Functional characterization of tissue factor in von Willebrand factor-dependent thrombus formation under whole blood flow conditions

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Abstract

Von Willebrand factor (VWF) plays an important role in mediating platelet adhesion and aggregation under high shear rate conditions. Such platelet aggregates are strengthened by fibrin-network formation triggered by tissue factor (TF). However, little is known about the role of TF in VWF-dependent thrombus formation under blood flow conditions. We evaluated TF in thrombus formation on immobilized VWF under whole blood flow conditions in an in vitro perfusion chamber system. Surface-immobilized TF amplified intra-thrombus fibrin generation significantly under both low and high shear flow conditions, while TF in sample blood showed no appreciable effects. Furthermore, immobilized TF enhanced VWF-dependent platelet adhesion and aggregation significantly under high shear rates. Neutrophil cathepsin G and elastase increased significantly intra-thrombus fibrin deposition on immobilized VWF–TF complex, suggesting the involvement of leukocyte inflammatory responses in VWF/TF-dependent mural thrombogenesis under these flow conditions. These results reveal a functional link between VWF and TF under whole blood flow conditions, in which surface-immobilized TF and VWF mutually contribute to mural thrombus formation, which is essential for normal hemostasis. By contrast, TF circulating in blood may be involved in systemic hypercoagulability, as seen in sepsis caused by severe microbial infection, in which neutrophil inflammatory responses may be active.

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Acknowledgments

This study was partly supported by the grant (No. 19591129) from the Ministry of Education, Culture, Sports, Science and Technology of Japan to M. Sugimoto.

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Authors and Affiliations

  1. Department of Anesthesiology, Nara Medical University, Kashihara, Nara, Japan

    Yasunori Matsunari & Masahiko Kawaguchi

  2. Department of Regulatory Medicine for Thrombosis, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan

    Mitsuhiko Sugimoto, Masaaki Doi & Hideto Matsui

Authors
  1. Yasunori Matsunari
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  2. Mitsuhiko Sugimoto
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Correspondence to Mitsuhiko Sugimoto.

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Conflict of interest

Mitsuhiko Sugimoto, Masaaki Doi, and Hideto Matsui belong to the Department of Regulatory medicine for Thrombosis, Nara Medical University, which was endowed by the Bayer Pharmaceutical Company, Japan. Other authors declare that they have no conflict of interest.

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Matsunari, Y., Sugimoto, M., Doi, M. et al. Functional characterization of tissue factor in von Willebrand factor-dependent thrombus formation under whole blood flow conditions. Int J Hematol 104, 661–668 (2016). https://doi.org/10.1007/s12185-016-2086-z

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  • DOI: https://doi.org/10.1007/s12185-016-2086-z

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