title: Variation in thromboxane B2 concentrations in serum and plasma in patients taking regular aspirin before and after clopidogrel therapy.
abstract: Dual antiplatelet therapy with aspirin and a P2Y12 antagonist is widely prescribed for the prevention of thrombotic events in patients with an acute coronary syndrome or undergoing percutaneous coronary intervention (PCI). It is recognised that there is inter-individual variation in the antiplatelet effects of both drugs. Recent data also suggest that P2Y12 antagonists can affect the response to aspirin. A direct indicator of the effect of aspirin on platelets is their ability to generate thromboxane, which if measured as the difference between the level of thromboxane B2 in serum and plasma ([TxB2]S-P) avoids the confounding effect of endogenous TxB2 production from other cells. We therefore analysed [TxB2]S-P as a measure of aspirin response in a group of 123 patients undergoing elective PCI before and after the introduction of clopidogrel. In a subgroup of 40 patients taking aspirin alone, we compared [TxB2]S-P and VerifyNow Aspirin for the assessment of aspirin response. There was a wide variation in plasma and serum TxB2 concentrations both before and after clopidogrel therapy but only 3.5% of patients had residual serum concentration of TxB2 > 10 ng/ml. There was a strong correlation between the pre and post clopidogrel levels of TxB2 (r ≥ 0.78; p = 0.001) and no significant difference in [TxB2]S-P. There was no correlation between the magnitude of response to clopidogrel response and the generation of thromboxane B2. Correlation between [TxB2]S-P and VerifyNow Aspirin was poor. We conclude that the use of a P2Y12 antagonist does not influence the effect of aspirin on the ability of platelets to generate thromboxane. Therefore, measurement of TxB2 levels in serum, after subtracting the contribution from plasma, provides a measure of the response to aspirin in patients taking dual antiplatelet therapy.
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, University of Glasgow , Glasgow , UK .
authors.forename: Richard I S
authors.initials: RI
authors.lastname: Good
authors.forename: Anne
authors.initials: A
authors.lastname: McGarrity
authors.forename: Rory
authors.initials: R
authors.lastname: Sheehan
authors.forename: Tina E
authors.initials: TE
authors.lastname: James
authors.forename: Helen
authors.initials: H
authors.lastname: Miller
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stephens
authors.forename: Stuart
authors.initials: S
authors.lastname: Watkins
authors.forename: Alex
authors.initials: A
authors.lastname: McConnachie
authors.forename: Alison H
authors.initials: AH
authors.lastname: Goodall
authors.forename: Keith G
authors.initials: KG
authors.lastname: Oldroyd
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013929:Thromboxane B2 / Q000097:blood*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: Aspirin; P2Y12 antagonists; coronary artery disease; platelet function assays; thromboxane