Biorheology of Platelet Activation in the Bloodstream Distal to Thrombus Formation

Jevgenia Zilberman-Rudenko, Asako Itakura, Jeevan Maddala, Sandra M. Baker-Groberg, Ralf Vetter, Erik I. Tucker, András Gruber, Christoph Gerdes, Owen J.T. McCarty

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Thrombus growth at the site of vascular injury is mediated by the sequential events of platelet recruitment, activation and aggregation concomitant with the initiation of the coagulation cascade, resulting in local thrombin generation and fibrin formation. While the biorheology of a localized thrombus formation has been well studied, it is unclear whether local sites of thrombin generation propagate platelet activation within the bloodstream. In order to study the physical biology of platelet activation downstream of sites of thrombus formation, we developed a platform to measure platelet activation and microaggregate formation in the bloodstream. Our results show that thrombi formed on collagen and tissue factor promote activation and aggregation of platelets in the bloodstream in a convection-dependent manner. Pharmacological inhibition of the coagulation factors (F) X, XI or thrombin dramatically reduced the degree of distal platelet activation and microaggregate formation in the bloodstream without affecting the degree of local platelet deposition and aggregation on a surface of immobilized collagen. Herein we describe the development and an example of the utility of a platform to study platelet activation and microaggregate formation in the bloodstream (convection-limited regime) relative to the local site of thrombus formation.

Original languageEnglish (US)
Pages (from-to)496-508
Number of pages13
JournalCellular and Molecular Bioengineering
Volume9
Issue number4
DOIs
StatePublished - Dec 1 2016

Keywords

  • Biophysics
  • Factor X
  • Factor XI
  • Physical biology
  • Platelets
  • Shear
  • Thrombin

ASJC Scopus subject areas

  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)

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