Anucleate fragments with alpha and dense granules
Expansion
Origin: megakaryocytes in the bone marrow shed cytoplasmic fragments. Each produces several thousand platelets, and the lifespan is 7 to 10 days, which is why aspirin’s irreversible effect lasts that long.
Structure: anucleate, 2 to 3 micrometres, with a peripheral zone (glycoprotein receptors), a sol-gel zone (microtubules maintaining the discoid shape and actin for shape change), and an organelle zone containing the granules.
Two granule types
- Alpha granules, more numerous: fibrinogen, von Willebrand factor, factor V, platelet derived growth factor, P-selectin, thrombospondin
- Dense granules: ADP, ATP, calcium, serotonin
“Alpha for the big proteins, dense for the small molecules.”
The dense granule contents are the amplifiers: released ADP recruits further platelets through the P2Y12 receptor, which is exactly the target of clopidogrel, ticagrelor and prasugrel.
Key surface glycoproteins
- GpIb binds von Willebrand factor for adhesion. Deficient in Bernard-Soulier syndrome
- GpIIb/IIIa binds fibrinogen for aggregation, the final common pathway. Deficient in Glanzmann’s thrombasthenia, and blocked by abciximab
Three steps: adhesion, activation with shape change and release, then aggregation.