Mature platelets or thrombocytes are irregularly shaped disks with an average life span in blood of about 5 to 7 days. After platelets are released from the bone marrow, about two-thirds of them enter systemic circulation, whereas the remaining portion is sequestered in the spleen. The average human maintains approximately 150,000 to 450,000 platelets per microliter of circulating blood.
Role in Coagulation
In an acute bleeding episode, platelets stored in the spleen can immediately be released into circulation. Platelets circulating in the blood are essentially inactive until they become activated by chemicals, blood vessel trauma, or a bleeding episode. When platelets react to extravascular tissue or chemicals, they undergo changes known as platelet activation to become active participants in the hemostasis process.
The final outcome of platelet activation includes enhancement of platelet procoagulant interactions between chemicals, endothelium, and other platelets to form multiple platelet aggregation events and the generation of a platelet-rich thrombus to terminate bleeding. Antiplatelet drug therapy either partially or completely prevents platelets from participating in thrombus formation, extension, and embolization.
Clopidogrel, Prasugrel, or Ticagrelor?
Currently, aspirin plus clodpiogrel (Plavix) or prasugrel (Effient) is the standard of care for antiplatelet therapy with unstable angina, non-ST elevation myocardial infarction (NSTEMI), acute MI (STEMI), or percutaneous coronary intervention (PCI). The FDA recently approved ticagrelor (Brilinta) for use with low-dose aspirin (75-100 mg) to decrease the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS). It is expected to compete with clopidogrel and prasugrel.
Additional Points to Consider
Due to their metabolic pathway, drug–drug interactions with each of these drugs may require close monitoring. Platelet response to prasugrel is less variable than with clopidogrel, but it has a higher bleeding risk.1
Ticagrelor decreases platelet reactivity more rapidly and more completely than clopidogrel and recovery of platelet function after discontinuing the drug is about twice as rapid with ticagrelor as with clopidogrel.2,3 Ticagrelor is contraindicated for use in patients with severe hepatic impairment. Twice daily dosing with ticagrelor may contribute to compliance issues and affect therapeutic outcomes. Although generally self-limiting, ticagrelor can cause dyspnea, bradyarrhythmias, and increased uric acid and creatinine levels.4
Mr. Brown is professor emeritus of clinical pharmacy and a clinical pharmacist at Purdue University College of Pharmacy, Nursing, and Health Sciences, Department of Pharmacy Practice, West Lafayette, Indiana.
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