Reversal of the anti-platelet effects of aspirin and clopidogrel

. Background: Guidelines recommend stopping aspirin and clopidogrel 7 to 10 days before surgery to allow time for replacement of permanently inhibited platelets by newly released uninhibited platelets.Objectives: The purpose of the present study was to determine the rate of offset of the anti-platelet effects of aspirin and clopidogrel after stopping treatment and the proportion of untreated donor platelets that are required to reverse their anti-platelet effects.Methods: Cohort 1 consisted of 15 healthy subjects who received aspirin 81 mg day-1 or clopidogrel 75 mg day-1 for 7 days and underwent serial blood sampling until platelet function testing results normalized. Cohort 2 consisted of 36 healthy subjects who received aspirin 325 mg day-1, clopidogrel 75 mg day-1, aspirin 81 mg day-1 plus clopidogrel 75 mg day-1 or no treatment for 7 days and underwent a single blood sampling.Results: In cohort 1, arachidonic acid (AA)-induced light transmission aggregation (LTA) returned to baseline levels in all subjects within 4 days of stopping aspirin, coinciding with the partial recovery of plasma thromboxane B2 concentrations. ADP-induced LTA did not return to baseline levels until 10 days after stopping clopidogrel. In cohort 2, AA-induced LTA in patient treated with aspirin reached control levels after mixing with 30% untreated donor platelets whereas ADP-induced LTA in patients treated with clopidogrel reached control levels only after the addition of 90% or more donor platelets.Conclusions: Platelet aggregation recovers within 4 days of stopping aspirin but clopidogrel must be stopped for 10 days to achieve a normal aggregatory response.