Recovery of platelet function after discontinuation of clopidogrel treatment in healthy volunteers

Abstract

Aims To study the recovery of platelet function after discontinuation of clopidogrel treatment in healthy volunteers. Methods Ten healthy volunteers were treated with clopidogrel (75 mg day x1 ) for 7 days. CD62P expression and PAC-1 binding were measured by¯ow cytometry.Results Adenosine diphosphate (ADP, 30 mM)-induced platelet responses were almost completely inhibited by clopidogrel. After discontinuation of the drug, platelet function gradually increased and complete recovery was seen 7 days after the last clopidogrel dose. The mean difference (95% CI) for ADP-induced PAC-1 binding (¯uorescence intensity) between baseline and 7 days after the last dose was 0.01 (0.61, x0.59). Single cell analysis provides direct evidence for an irreversible mode of action of clopidogrel. Conclusions This is the ®rst report to directly demonstrate irreversibility of clopidogrel action in humans.

Optimal Timing of Discontinuation of Clopidogrel and Risk of Blood Transfusion After Coronary Surgery - Propensity Score Analysis -

“…21, 22 As a consequence, several studies have analyzed the impact of preoperative clopidogrel on hemorrhagic complications. [4][5][6][7][8][9][10][11][12] The present data confirm that preoperative clopidogrel was an independent predictor for transfusion of blood products, supporting the discontinuation of clopidogrel >5 days before surgery in order to avoid the risk of transfusion. The present data confirm the American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations, which certainly endorse the acute use of clopidogrel, recommending its withholding for at least 5 days before CABG surgery.…”

Guideline on the management of bleeding in patients on antithrombotic agents

“…Clopidogrel may show a delayed onset of platelet inhibition of 4-8 h because it requires activation by two-stage hepatic metabolism. Prasugrel, which requires one-stage activation, and ticagrelor exert anti-platelet effect within 2-4 h. The active metabolites of clopidogrel and prasugrel have short plasma half-lives (c. 0Á5 and c. 7 h respectively), although as they are irreversible P2Y 12 antagonists, the duration of platelet inhibition may be 5-7 d (Weber et al, 2001;Price et al, 2011) or longer (Li et al, 2012). Ticagrelor is a potent P2Y 12 antagonist that has a plasma half-life of 8-12 h and is more reversible than clopidogrel and prasugrel.…”

Functional and Biochemical Evaluation of Platelet Aspirin Resistance After Coronary Artery Bypass Surgery

“…Thereafter, aliquots of 25 L PRP were incubated with 5 L anti-CD62P-FITC (Beckman Coulter, Krefeld, Germany) for 30 minutes and diluted with 500 L Isotone for analysis on an EPICS-XL cytometer (Beckman Coulter), as described elsewhere. 16 …”