Antiplatelet Therapy

Antiplatelet medications inhibit platelet aggregation. They are used to prevent thrombosis in conditions like ischemic stroke or myocardial infarction in at risk patients. There are 3 major classes of antiplatelet medications, including COX inhibitors, like aspirin; GP IIb/IIIa inhibitors, like tirofiban; and P2Y12 ADP receptor antagonists, like clopidogrel.
Alright, let’s start with how platelet aggregation works. When there’s a vascular injury in the body, platelets aggregate, or stick to the damaged vessel wall. In addition, they release various activating substances, including thromboxane A2 and adenosine diphosphate or ADP, that cause platelets to express a surface receptor called glycoprotein IIb/IIIa or GPIIb/IIIa. These receptors help platelet-to-platelet adhesion and binding to fibrinogen, a protein that circulates in the blood, which helps link platelets together. This allows platelets to rapidly aggregate at the site of injury and form a platelet plug, as red blood cells become enmeshed in the fibrin. This forms a clot that can help stop the bleeding.
Now, let’s focus on clopidogrel, a commonly used antiplatelet medication. Clopidogrel works by binding to a specific ADP receptor on the platelets called P2Y12, which prevents ADP from binding to it. Without ADP, the platelets can’t express GPIIb/IIIa on their surface, which inhibits clot formation. Okay, let’s look at the side effects of clopidogrel. While the medication is generally well-tolerated, clopidogrel increases bleeding risk which can lead to epistaxis, or bloody nose, and easy bruising. Other common side effects can include indigestion, diarrhea, abdominal pain, or rash.
Rarely, thrombotic thrombocytopenic purpura, or TTP, can occur within the first 2 weeks of therapy. TTP causes clotting in small blood vessels throughout the body, resulting in thrombocytopenia, or a low platelet count, as well as fever, hemolytic anemia, renal and neurologic dysfunction. TPP is considered a medical emergency which can be fatal. As far as contraindications go, clopidogrel should not be given when active bleeding is present, like with recent trauma, bleeding peptic ulcers, or intracranial hemorrhage. Clopidogrel should also be used with caution in patients with hepatic or renal impairment. Now, for clopidogrel to be effective, it needs to be converted in the liver into its active form by the enzyme CYP2C19. If a patient has 2 non-functional copies of the CYP2C19 gene, which codes for this liver enzyme, the medication won’t be effective; and this can put patients at an increased risk of adverse events like stroke or myocardial infarction. In fact, clopidogrel has a Black Box warning for patients who lack this enzyme and are referred to as CYP2C19 poor metabolizers. Instead of clopidogrel, these patients should be prescribed another type of antiplatelet medication.