The key events of thrombus formation: platelet adhesion and aggregation

Biomech Model Mechanobiol. 2020 Jun;19(3):943-955. doi: 10.1007/s10237-019-01262-x. Epub 2019 Nov 21.

Abstract

Thrombus formation is a complex, dynamic and multistep process, involving biochemical reactions, mechanical stimulation, hemodynamics, and so on. In this study, we concentrate on its two crucial steps: (i) platelets adhered to a vessel wall, or simply platelet adhesion, and (ii) platelets clumping and arrested to the adherent platelets, named platelet aggregation. We report the first direct simulation of three modes of platelet adhesion, detachment, rolling adhesion and firm adhesion, as well as the formation, disintegration, arrestment and consolidation of platelet plugs. The results show that the bond dissociation in the detachment mode is mainly attributed to a high probability of rupturing bonds, such that any existing bond can be quickly ruptured and all bonds would be completely broken. In the rolling adhesion, however, it is mainly attributed to the strong traction from the shear flow or erythrocytes, causing that the bonds are ruptured at the trailing edge of the platelet. The erythrocytes play an important role in platelet activities, such as the formation, disintegration, arrestment and consolidation of platelet plugs. They exert an aggregate force on platelets, a repulsion at a near distance but an attraction at a far distance to the platelets. This aggregate force can promote platelets to form a plug and/or bring along a part of a platelet plug causing its disintegration. It also greatly influences the arrestment and consolidation of platelet plugs, together with the adhesive force from the thrombus.

Keywords: Numerical modeling; Platelet adhesion; Platelet aggregation; Thrombus formation.

MeSH terms

  • Blood Platelets / physiology*
  • Computer Simulation
  • Erythrocytes / cytology
  • Humans
  • Imaging, Three-Dimensional
  • Ligands
  • Microcirculation
  • Models, Theoretical
  • Monte Carlo Method
  • Platelet Activation
  • Platelet Adhesiveness*
  • Platelet Aggregation*
  • Shear Strength
  • Stress, Mechanical
  • Thrombosis / physiopathology*

Substances

  • Ligands