Reversal of the anti-platelet effects of aspirin and clopidogrel

J Thromb Haemost. 2012 Apr;10(4):521-8. doi: 10.1111/j.1538-7836.2012.04641.x.


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 B(2) 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.

Publication types

  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate
  • Adult
  • Arachidonic Acid
  • Aspirin / administration & dosage*
  • Biomarkers / blood
  • Biomarkers / urine
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Clopidogrel
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Ontario
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Function Tests
  • Platelet Transfusion
  • Recovery of Function
  • Thromboxane B2 / analogs & derivatives
  • Thromboxane B2 / blood
  • Thromboxane B2 / urine
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Time Factors


  • Biomarkers
  • Platelet Aggregation Inhibitors
  • Arachidonic Acid
  • Thromboxane B2
  • Adenosine Diphosphate
  • 11-dehydro-thromboxane B2
  • Clopidogrel
  • Ticlopidine
  • Aspirin