Methods to Determine the Lagrangian Shear Experienced by Platelets during Thrombus Growth

PLoS One. 2015 Dec 14;10(12):e0144860. doi: 10.1371/journal.pone.0144860. eCollection 2015.

Abstract

Platelets can become activated in response to changes in flow-induced shear; however, the underlying molecular mechanisms are not clearly understood. Here we present new techniques for experimentally measuring the flow-induced shear rate experienced by platelets prior to adhering to a thrombus. We examined the dynamics of blood flow around experimentally grown thrombus geometries using a novel combination of experimental (ex vivo) and numerical (in silico) methodologies. Using a microcapillary system, platelet aggregate formation was analysed at elevated shear rates in the presence of coagulation inhibitors, where thrombus formation is predominantly platelet-dependent. These approaches permit the resolution and quantification of thrombus parameters at the scale of individual platelets (2 μm) in order to quantify real time thrombus development. Using our new techniques we can correlate the shear rate experienced by platelets with the extent of platelet adhesion and aggregation. The techniques presented offer the unique capacity to determine the flow properties for a temporally evolving thrombus field in real time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / pharmacology
  • Blood Flow Velocity
  • Blood Platelets / cytology*
  • Blood Platelets / drug effects
  • Cells, Cultured
  • Hirudins / pharmacology
  • Humans
  • Imaging, Three-Dimensional
  • Kinetics
  • Microscopy, Confocal
  • Models, Statistical*
  • Platelet Adhesiveness / drug effects
  • Platelet Aggregation / drug effects
  • Stress, Mechanical*
  • Thrombosis / blood*

Substances

  • Anticoagulants
  • Hirudins

Grants and funding

This research was supported by the National Health and Medical Research Council of Australia, the National Heart Foundation of Australia, the Victorian Life Sciences Computation Initiative (VLSCI) (grant VR0023 using the Peak Computing Facility at the University of Melbourne, an initiative of the Victorian Government, Australia) and by the Multi-modal Australian ScienceS Imaging and Visualisation Environment (MASSIVE) (www.massive.org.au) (grant MONASH024).