Expansion
Adhesion, activation, aggregation, then providing a surface for coagulation
Expansion
- Adhesion: von Willebrand factor bridges exposed subendothelial collagen and platelet GPIb
- Activation: shape change, and release of granule contents
- Dense granules: ADP, calcium, serotonin
- Alpha granules: fibrinogen, von Willebrand factor, factor V, platelet-derived growth factor
- Synthesis of thromboxane A2 via cyclo-oxygenase
- Aggregation: GPIIb/IIIa receptors are exposed and bind fibrinogen, linking platelets together
- Procoagulant surface: phosphatidylserine is exposed, on which the coagulation complexes assemble
Platelets live 7 to 10 days and are produced from megakaryocytes under thrombopoietin.
Drug targets map onto the steps:
- Aspirin: irreversible cyclo-oxygenase inhibition, blocking thromboxane
- Clopidogrel, ticagrelor: block the P2Y12 ADP receptor
- Abciximab, tirofiban: block GPIIb/IIIa, the final common pathway
- Dipyridamole: phosphodiesterase inhibition
Disorders illustrate each step: von Willebrand disease (adhesion), Bernard-Soulier (GPIb), and Glanzmann thrombasthenia (GPIIb/IIIa).