Reversal of the anti‐platelet effects of aspirin and clopidogrel

• Published in: Journal of thrombosis and haemostasis Vol. 10; no. 4; pp. 521 - 528
• Main Authors: LI, C., HIRSH, J., XIE, C., JOHNSTON, M. A., EIKELBOOM, J. W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2012
• Subjects: Adenosine Diphosphate; Adult; Arachidonic Acid; aspirin; Aspirin - administration & dosage; Biomarkers - blood; Biomarkers - urine; Blood Platelets - drug effects; Blood Platelets - metabolism; clopidogrel; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Ontario; peri‐operative treatment; platelet aggregation; 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; Ontario
• ISSN: 1538-7933; 1538-7836; 1538-7836
• 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 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.