Which of the following is an inhibitor of platelet aggregation: Prostacyclin I (Prostacyclin), Thromboxane A2, Adenosine diphosphate (ADP), or Serotonin?

Inhibitors of Platelet Aggregation

Prostacyclin I (Prostacyclin) is the only inhibitor of platelet aggregation among the options provided. Prostacyclin is the dominant prostanoid produced by endothelial cells that antagonizes platelet aggregation by interacting with platelet IP receptors 1.

Mechanism of Action of Each Option

Prostacyclin I (PGI2)

• Primary action: Potent inhibitor of platelet aggregation
• Mechanism:
  • Increases cyclic AMP (cAMP) levels in platelets 2
  • Interacts with platelet IP receptors to antagonize aggregation 1
  • Produces local smooth muscle relaxation and vasodilation 1
  • Inhibits platelet shape change and prevents development of procoagulant activity 3
  • Reduces platelet adhesion by inhibiting platelet spreading 4

Thromboxane A2 (TXA2)

• Primary action: Promotes platelet aggregation
• Mechanism:
  • Potent proaggregatory and vasoconstrictive eicosanoid 1
  • Major COX product formed by platelets 1
  • Produced by platelets containing COX-1, which converts arachidonic acid to TXA2 1

Adenosine Diphosphate (ADP)

• Primary action: Promotes platelet aggregation
• Mechanism:
  • Binds to P2Y12 receptors on platelets 1
  • Induces platelet aggregation through G-protein coupled receptors 1
  • Thienopyridines (like clopidogrel and ticlopidine) work by inhibiting ADP-induced platelet aggregation 1

Serotonin

• Primary action: Promotes platelet aggregation
• Mechanism:
  • Released during platelet activation
  • Contributes to platelet aggregation and vasoconstriction

Clinical Relevance

The balance between prostacyclin (inhibitor) and thromboxane A2 (promoter) is crucial for hemostasis and thrombosis prevention. This balance is referred to as the prostacyclin:thromboxane A2 ratio 2.

In atherosclerotic disease, COX-2 inhibitors can disrupt this balance by:

• Reducing endothelial production of prostacyclin (the inhibitor)
• Leaving platelet production of TXA2 (the promoter) intact
• Creating an imbalance that may increase risk for thrombotic cardiovascular events 1

This explains why aspirin is effective for arterial thrombosis - it reduces COX-1-dependent production of platelet TXA2 while preserving some prostacyclin production 1.

Summary of Effects on Platelet Aggregation

Agent	Effect on Platelet Aggregation	Mechanism
Prostacyclin I	Inhibits	Increases cAMP, antagonizes IP receptors
Thromboxane A2	Promotes	Potent proaggregatory eicosanoid
ADP	Promotes	Activates P2Y12 receptors
Serotonin	Promotes	Contributes to aggregation and vasoconstriction