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Figure 1 Platelet activation is an important early step in the pathophysiology of atherothrombosis. Platelet activation involves: 1) a shape change in which the platelet membrane surface area is greatly increased; 2) the secretion of pro-inflammatory, prothrombotic, adhesive, and chemotactic mediators (release reaction), that propagate, amplify, and sustain the atherothrombotic process; and 3) the activation of the glycoprotein (GP) IIb/IIIa receptor from its inactive form. Multiple agonists including thromboxane A₂ (TXA₂), adenosine diphosphate (ADP), thrombin, serotonin, epinephrine, and collagen, can activate the platelet and thus contribute toward establishing the environmental conditions necessary for atherothrombosis to occur. Aspirin inhibits the production of thromboxane A₂ by its effect on the enzyme cyclooxygenase (COX) 1. The ADP receptor antagonists clopidogrel and ticlopidine prevent the binding of ADP to its receptor. The effect of combining aspirin and clopidogrel is synergistic in preventing platelet aggregation. Antithrombins such as unfractionated or low-molecular-weight heparin, hirudin, or bivalirudin are important in interfering with both thrombin-induced platelet activation and coagulation. The GP IIb/IIIa receptor antagonists act at a later step in the process by preventing fibrinogen mediated cross-linking of platelets, which have already become activated. ATP = adenosine triphosphate; PAI = plasminogen activator inhibitor; PDGF = platelet-derived growth factor; vWF = von Willebrand factor.