What is an inhibitor of platelet aggregation among the given options: (a) prostacyclin I (prostaglandin I2), (b) thromboxane A2, (c) adenosine diphosphate (ADP), (d) serotonin, (e) von Willebrand’s factor?

Inhibitors of Platelet Aggregation

Prostacyclin I (prostaglandin I2) is the correct answer as it is the only inhibitor of platelet aggregation among the given options. 1, 2

Mechanism of Action of Prostacyclin I

• Prostacyclin (PGI2) is the dominant prostanoid produced by endothelial cells in the vascular wall 1
• It functions as a potent vasodilator and is the most potent endogenous inhibitor of platelet aggregation discovered 2, 3
• Prostacyclin inhibits platelet aggregation by:
  • Increasing cyclic AMP levels in platelets 2, 4
  • Interacting with platelet IP receptors, thereby antagonizing aggregation 1
  • Inhibiting platelet spreading, which reduces adhesion to vascular surfaces 3

Comparison with Other Options

Thromboxane A2 (TXA2)

• TXA2 is the major COX product formed by platelets 1
• It is a potent proaggregatory and vasoconstrictive eicosanoid 1
• Platelets contain COX-1, which converts arachidonic acid to TXA2 1
• TXA2 promotes platelet aggregation, opposite to the effect of prostacyclin 1

Adenosine Diphosphate (ADP)

• ADP is a platelet agonist that promotes platelet aggregation 1
• It activates platelets through the P2Y12 receptor 1
• Thienopyridines (like clopidogrel and ticlopidine) work by blocking ADP-induced platelet aggregation 1
• ADP itself induces, rather than inhibits, platelet aggregation 1

Serotonin

• Serotonin is a platelet activator, not an inhibitor 1
• It is released from platelets during activation and promotes further aggregation 1

Von Willebrand Factor

• Von Willebrand factor facilitates platelet adhesion to damaged endothelium 1
• It mediates platelet-vessel wall interactions, promoting rather than inhibiting platelet aggregation 1

Clinical Significance of Prostacyclin

• The balance between prostacyclin (inhibitor) and thromboxane A2 (promoter) is crucial for normal hemostasis 2
• Prostacyclin is released from the pulmonary circulation into the arterial circulation, providing continuous anti-aggregatory effects 2, 4
• Reduced prostacyclin production has been implicated in diseases such as atherosclerosis and diabetes 4
• Therapeutic applications of prostacyclin include use during extracorporeal circulation procedures and potential applications in peripheral vascular disease 4, 5

Pharmacological Implications

• Non-selective COX inhibitors (like aspirin) inhibit both COX-1 and COX-2, affecting both TXA2 and prostacyclin production 1
• Selective COX-2 inhibitors reduce prostacyclin production while leaving TXA2 production intact, potentially increasing thrombotic risk 1
• The prostacyclin:thromboxane A2 ratio is important in controlling thrombus formation 2
• Prostacyclin has been shown to be 100-fold more potent than prostaglandin E1 or D2 in inhibiting platelet aggregation 5