The regulation of platelet aggregation is complex, stepwise, multifactorial and not fully deciphered.
Many receptors, some of them intertwined through enzymatic pathways they activate, are involved.
The initiators of aggregation are von Willebrand factor (vWf) from endothelial cells (which binds to GPIb/V/IX), and collagen from the vascular wall.
Sustained aggregation is induced by subtances that bind to GPCRs (G protein coupled receptors) :
- Thromboxane A2, whose production is inhibited by Aspirin (Acetyl Salicylic Acid ASA).
- ADP (adenosine di phosphate), which binds to the P2Y12 receptor
- Thrombin, produced by initiation of plasma coagulation, which binds to Protease Activated Receptors (PARs)
Stabilized aggregation is the consequence of the binding of fibrinogen (hence bridging platelets to each other) to the GPIIb/IIIa receptor
Platelet aggregation can be inhibited by :
- Inhibitors of TxA2 production : aspirin, and non-steroid anti-inflammatory drugs.
- Inhibitors of the P2Y12 receptor, such as ticlopidine, clopidogrel, prasugrel, cangrelor.
- Direct Thrombin inhibitors (DTIs) such as ximelagatran (discontinued), desirudin, lepirudin, dabigatran, bivalirudin. All these drugs are also inhibitors of plasma coagulation where thrombin plays a key role.
- Inhibitors of von Willebrand factor (being studied).
- Inhibitors of the GPIIb/IIIa receptor such as abciximab, eptifibatide, tirofiban.
Thrombosis : platelet aggregation inhibitors are essentially used in the
treatment or prevention of arterial thrombosis