Activation

Platelet activation takes place after attachment and adhesion events or after other stimuli that triggeres activation mechanisms such as thromboxane A2, ADP, thrombin or PAF (platelet activating factor, released from endothelial cells, PMN or monocytes).

In a first step of activation, platelets undergo shape change, cytoskeleton rearrangement and organelle centralization. Release of dense granule contents (ADP and ATP) and serotonin, occurs. In a second step, there is alpha granule release of fibrinogen, fibronectin and vWF, exposure of fibrinogen and fibronectin receptors on platelet surface, and finally, release of arachidonic acid to be converted to thromboxane A2, which is a powerful mediator of platelet aggregating response.

Cyclooxygenase is the key enzyme responsible for synthesis of thromboxane A2 in platelets. Aspirin and other anti-inflammatory drugs interfere with an early step of prostaglandin pathway, suppressing the formation of pro-aggregatory cyclic endoperoxides precursors of thromboxane A2.

The following animations show detailed information on most of the receptors, molecular mechanisms, signaling pathways and platelet responses that are triggered after activation, as well as their regulatory and modulatory mechanisms:

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It is important to point out that the information contained in the animation should not be considered as facts but models subjected to debate:

  • Actin polymerization and lamellipodia formation
  • Granule content secretion
  • Arachidonic acid mobilization
  • Phospholipid scrambling and coagulation
  • PAR thrombin receptors (Gi, Gq and G12/13)
  • Thromboxane A2 receptors (Gq and G12/13)
  • P2Y1 and P2Y12 ADP receptors (Gi and Gq)
  • Glycoprotein Ia-IIa
  • Glycoprotein Ib-IX-V
  • Glycoprotein IIb-IIIa
  • Glycoprotein IV
  • Glycoprotein VI

Bibliography

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Rao GH, White JG. Role of arachidonic acid metabolism in human platelet activation and irreversible aggregation. Am J Hematol. 1985; 19: 339-47. 10.1002/ajh.2830190404.

Diaz-Ricart M, Tandon NN, Gomez-Ortiz G, Carretero M, Escolar G, Ordinas A, Jamieson GA. Antibodies to CD36 (GPIV) inhibit platelet adhesion to subendothelial surfaces under flow conditions. Arterioscler Thromb Vasc Biol. 1996; 16: 883-8. 10.1161/01.atv.16.7.883.

Rivera J, Lozano ML, Navarro-Nunez L, Vicente V. Platelet receptors and signaling in the dynamics of thrombus formation. Haematologica. 2009; 94: 700-11. 10.3324/haematol.2008.003178.

Cattaneo M. Molecular defects of the platelet P2 receptors. Purinergic Signal. 2011; 7: 333-9. 10.1007/s11302-011-9217-z.

Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost. 2011; 105 Suppl 1: S13-33. 10.1160/THS10-11-0720.

van der Meijden PEJ, Heemskerk JWM. Platelet biology and functions: new concepts and clinical perspectives. Nature Reviews Cardiology. 2019; 16: 166-79. 10.1038/s41569-018-0110-0.