The effects of arterial flow on platelet activation, thrombus growth, and stabilization

Cardiovasc Res. 2013 Jul 15;99(2):342-52. doi: 10.1093/cvr/cvt110. Epub 2013 May 10.


Injury of an arterial vessel wall acutely triggers a multifaceted process of thrombus formation, which is dictated by the high-shear flow conditions in the artery. In this overview, we describe how the classical concept of arterial thrombus formation and vascular occlusion, driven by platelet activation and fibrin formation, can be extended and fine-tuned. This has become possible because of recent insight into the mechanisms of: (i) platelet-vessel wall and platelet-platelet communication, (ii) autocrine platelet activation, and (iii) platelet-coagulation interactions, in relation to blood flow dynamics. We list over 40 studies with genetically modified mice showing a role of platelet and plasma proteins in the control of thrombus stability after vascular injury. These include multiple platelet adhesive receptors and other junctional molecules, components of the ADP receptor signalling cascade to integrin activation, proteins controlling platelet shape, and autocrine activation processes, as well as multiple plasma proteins binding to platelets and proteins of the intrinsic coagulation cascade. Regulatory roles herein of the endothelium and other blood cells are recapitulated as well. Patient studies support the contribution of platelet- and coagulation activation in the regulation of thrombus stability. Analysis of the factors determining flow-dependent thrombus stabilization and embolus formation in mice will help to understand the regulation of this process in human arterial disease.

Keywords: Coagulation; Platelets; Shear rate; Stabilization; Thrombus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arteries / injuries
  • Arteries / metabolism*
  • Arteries / pathology
  • Arteries / physiopathology
  • Biomechanical Phenomena
  • Blood Coagulation*
  • Hemodynamics*
  • Humans
  • Mechanotransduction, Cellular*
  • Platelet Activation*
  • Regional Blood Flow
  • Stress, Mechanical
  • Thrombosis / blood
  • Thrombosis / pathology
  • Thrombosis / physiopathology*
  • Vascular System Injuries / blood
  • Vascular System Injuries / pathology
  • Vascular System Injuries / physiopathology*