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Preoperative Assessment of Platelet Inhibition by Plavix

Preoperative management of patients who are taking Plavix and require an invasive procedure or surgery can be problematic. Operating on patients who are taking Plavix is associated with excessive bleeding, but discontinuing Plavix therapy prior to surgery has been associated with a 20% incidence of ischemic events.

At least 3 clinical practice guidelines provide direction regarding the timing of surgery in patients receiving Plavix. Each of these guidelines recommends discontinuing Plavix for at least 3 to 7 days prior to surgery to allow platelet function to return to normal and decrease the risk of bleeding.

The American College of Chest Physicians Evidence Based Clinical Practice Guidelines from 2008 state that platelet function returns to normal 7 days after the last dose of clopidogrel (Chest 2008;133:71S-105S, specifically page 217S)

The Society of Thoracic Surgeons Clinical Practice Guidelines, which were updated in 2011, state that previous reports recommended a 5 to 7 day delay after discontinuation of clopidogrel in patients requiring coronary artery bypass graft surgery to lessen bleeding (Ann Thorac Surg 2011;91:944-82, specifically page 951).

In between these two sets of guidelines is an update from May 2011 by the American College of Cardiology Foundation/American Heart Association for management of patients with unstable angina/non-ST elevation myocardial infarction. This document recommended withdrawing clopidogrel for at least 5 days prior to coronary artery bypass graft surgery (JACC 2011;57:1920-59).

All of these recommendations are based on the pharmacokinetics of clopidogrel. Inhibition of platelet aggregation can usually be detected 2 hours after a 300–600 mg loading dose of clopidogrel. Peak effect is usually evident at 6 hours after treatment. Clopidogrel irreversibly inhibits platelet function by blocking the binding of ADP to the platelet P2Y12 receptor. Platelets blocked by clopidogrel are affected for the remainder of their lifespan, which is 7-10 days.

These recommendations do not take into account individualized response to drugs. Approximately 40% of patients have suboptimal antiplatelet response to clopidogrel. Patients who are hyporesponders or nonresponders would be expected to normalize platelet function even sooner than 5 to 7 days after discontinuing clopidogrel.

An individual’s response to clopidogrel can only be determined by performing platelet function testing.

Saint Luke’s Regional Laboratories offers the VerifyNow test. This test has been named the P2Y12 Response Assay to avoid confusion with other tests such as the platelet function assay (PFA-100) and platelet aggregation.

Determination of the percent of platelet inhibition can be used preoperatively to determine if a patient who has been taking Plavix is at increased risk of bleeding. Values between 0 -20% are associated with minimal bleeding risk. More than 50% of patients achieve this level of inhibition within 3 days after discontinuing clopidogrel. Testing may reduce unnecessary surgical delays.

Specimen collection requirements were previously discussed in the January 2009 issue of the Clinical Laboratory Letter.

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