Variation in thromboxane B2 concentrations in serum and plasma in patients taking regular aspirin before and after clopidogrel therapy

Goodwin, R. I.S., McGarrity, A., Sheehan, R., James, T. E., Miller, H., Stephens, J., Watkins, S., McConnachie, A. , Goodall, A. H. and Oldroyd, K. G. (2015) Variation in thromboxane B2 concentrations in serum and plasma in patients taking regular aspirin before and after clopidogrel therapy. Platelets, 26(1), pp. 17-24. (doi: 10.3109/09537104.2013.870334) (PMID:24433337)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McConnachie, Professor Alex and Oldroyd, Dr Keith and Goodwin, Dr Richard and McGarrity, Ms Anne and Miller, Mrs Helen
Authors: Goodwin, R. I.S., McGarrity, A., Sheehan, R., James, T. E., Miller, H., Stephens, J., Watkins, S., McConnachie, A., Goodall, A. H., and Oldroyd, K. G.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Science and Engineering
Journal Name:Platelets
ISSN:0953-7104
ISSN (Online):1369-1635
Published Online:16 January 2014

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
431031Does variation in response to oral antiplatelet therapy influence outcome in patients undergoing PCI?Richard GoodBritish Heart Foundation (BHF)FS/06/031CAMS - CARDIOVASCULAR SCIENCE