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DOI: 10.1160/TH09-08-0527
A comparison of platelet function tests and thromboxane metabolites to evaluate aspirin response in healthy individuals and patients with coronary artery disease
Financial support: The study was financially supported by the Danish Research Agency (grant no. 2101–05–0052).Publication History
Received:
03 August 2009
Accepted after major revision:
01 February 2010
Publication Date:
22 November 2017 (online)
Summary
Individualised antiplatelet therapy and platelet function testing have attracted considerable clinical interest, but several aspects of test performance have not been thoroughly evaluated. We investigated repeatability and concordance of light transmission aggregometry (LTA) induced with arachidonic acid (AA) 1.0 mM, PFA-100® induced with collagen/epinephrine, multiple electrode aggregometry (MEA) induced with AA 0.5 or 0.75 mM and VerifyNow® Aspirin. Patients with stable coronary artery disease (n=43) and healthy individuals (n=21) were included. All tests were performed in duplicate at baseline in healthy individuals and in duplicate for four days in all study participants during aspirin treatment. Serum and urinary thromboxane metabolites were measured several times to evaluate cyclooxygenase-1 inhibition by aspirin. MEA was most sensitive for aspirin as treatment induced a 12-fold difference in AA-induced platelet aggregation. Coefficients of variation for duplicate measurements at baseline (0.4–12%), during aspirin treatment (3–46%) and for day-to-day variability (3–37%) differed markedly between tests and were lowest for VerifyNow®. The prevalence of aspirin low-responsiveness also differed between tests (0–9%) and the agreement was low: kappa≤0.21 for all tests compared with AA-induced LTA (reference test), which correlated best with VerifyNow® (r=0.43, p<0.001). Urinary thromboxane metabolites did not correlate with any platelet function test, whereas serum thromboxane correlated with VerifyNow® Aspirin (r=0.41, p=0.001). Overall, repeatability was moderate and the correlation between tests was low. VerifyNow® Aspirin proved most reproducible, and this was the only assay showing a significant positive correlation with serum thromboxane. This study demonstrated that conclusions based on platelet function testing strongly depend on the assay used.
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References
- 1 Antithrombotic Trialists’ Collaboration.. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Br Med J 2002; 324: 71-86.
- 2 Eikelboom JW, Hirsh J, Weitz JI. et al. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002; 105: 1650-1655.
- 3 Gum PA, Kottke-Marchant K, Welsh PA. et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003; 41: 961-965.
- 4 Chen WH, Lee PY, Ng W. et al. Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pretreatment. J Am Coll Cardiol 2004; 43: 1122-1126.
- 5 Chen WH, Cheng X, Lee PY. et al. Aspirin resistance and adverse clinical events in patients with coronary artery disease. Am J Med 2007; 120: 631-635.
- 6 Snoep JD, Hovens MM, Eikenboom JC. et al. Association of laboratory-defined aspirin resistance with a higher risk of recurrent cardiovascular events: a systematic review and meta-analysis. Arch Intern Med 2007; 167: 1593-1599.
- 7 Krasopoulos G, Brister SJ, Beattie WS. et al. Aspirin “resistance” and risk of cardiovascular morbidity: systematic review and meta-analysis. Br Med J 2008; 336: 195-198.
- 8 Grove EL, Kristensen SD. Update on oral antiplatelet therapy: principles, problems and promises. Future Cardiol 2009; 05: 247-258.
- 9 Born GV, Cross MJ. The aggregation of blood platelets. J Physiol 1963; 168: 178-195.
- 10 Bozic-Mijovski M, Rakusa M, Stegnar M. Variation in platelet function testing has a major influence on detection of aspirin resistance in healthy subjects. Pathophysiol Haemost Thromb 2008; 36: 84-90.
- 11 Gasparyan AY, Watson T, Lip GY. The role of aspirin in cardiovascular prevention: implications of aspirin resistance. J Am Coll Cardiol 2008; 51: 1829-1843.
- 12 Linnemann B, Schwonberg J, Mani H. et al. Standardization of light transmittance aggregometry for monitoring antiplatelet therapy: an adjustment for platelet count is not necessary. J Thromb Haemost 2008; 06: 677-683.
- 13 Nielsen HL, Kristensen SD, Thygesen SS. et al. Aspirin response evaluated by the VerifyNow Aspirin System and light transmission aggregometry. Thromb Res 2008; 123: 267-273.
- 14 Marcucci R, Paniccia R, Antonucci E. et al. Residual platelet reactivity is an independent predictor of myocardial injury in acute myocardial infarction patients on antiaggregant therapy. Thromb Haemost 2007; 98: 844-851.
- 15 Crescente M, Di Castelnuovo A, Iacoviello L. et al. PFA-100 closure time to predict cardiovascular events in aspirin-treated cardiovascular patients: A meta-analysis of 19 studies comprising 3,003 patients. Thromb Haemost 2008; 99: 1129-1131.
- 16 Patrono C, Ciabattoni G, Pugliese F. et al. Estimated rate of thromboxane secretion into the circulation of normal humans. J Clin Invest 1986; 77: 590-594.
- 17 Ciabattoni G, Maclouf J, Catella F. et al. Radioimmunoassay of 11-dehydrothromboxane B2 in human plasma and urine. Biochim Biophys Acta 1987; 918: 293-297.
- 18 Cattaneo M. Laboratory detection of ‘aspirin resistance‘: what test should we use (if any)?. Eur Heart J 2007; 28: 1673-1675.
- 19 Hedegaard SS, Hvas AM, Grove EL. et al. Optical platelet aggregation versus thromboxane metabolites in healthy individuals and patients with stable coronary artery disease after low-dose aspirin administration. Thromb Res 2009; 124: 96-100.
- 20 Gum PA, Kottke-Marchant K, Poggio ED. et al. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol 2001; 88: 230-235.
- 21 Wenaweser P, Dorffler-Melly J, Imboden K. et al. Stent thrombosis is associated with an impaired response to antiplatelet therapy. J Am Coll Cardiol 2005; 45: 1748-1752.
- 22 Tantry US, Bliden KP, Gurbel PA. Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation. J Am Coll Cardiol 2005; 46: 1705-1709.
- 23 Faraday N, Becker DM, Yanek LR. et al. Relation between atherosclerosis risk factors and aspirin resistance in a primary prevention population. Am J Cardiol 2006; 98: 774-779.
- 24 Gurbel PA, Bliden KP, DiChiara J. et al. Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study. Circulation 2007; 115: 3156-3164.
- 25 Lordkipanidze M, Pharand C, Schampaert E. et al. A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease. Eur Heart J 2007; 28: 1702-1708.
- 26 Muir AR, McMullin MF, Patterson C. et al. Assessment of aspirin resistance varies on a temporal basis in patients with ischaemic heart disease. Heart 2009; 95: 1225-1229.
- 27 Poulsen TS, Mickley H, Korsholm L. et al. Using the Platelet Function Analyzer-100 for monitoring aspirin therapy. Thromb Res 2007; 120: 161-172.
- 28 von Pape KW, Dzijan-Horn M, Bohner J. et al. Control of Aspirin Effect in Chronic Cardiovascular Patients Using two Whole Blood Platelet Function As-says: PFA-100 and Multiple Electrode Aggregometry. In: 36th Hemophilia Symposium Hamburg 2005. Springer Berlin Heidelberg; 2007. p. 243-51.
- 29 Siller-Matula JM, Gouya G, Wolzt M. et al. Cross validation of the Multiple Electrode Aggregometry. A prospective trial in healthy volunteers. Thromb Haemost 2009; 102: 397-403.
- 30 Mortensen J, Poulsen TS, Grove EL. et al. Monitoring aspirin therapy with the Platelet Function Analyzer-100. Scand J Clin Lab Invest 2008; 68: 786-792.
- 31 Nicholson NS, Panzer-Knodle SG, Haas NF. et al. Assessment of platelet function assays. Am Heart J 1998; 135: S170-S178.
- 32 Pedersen SB, Grove EL, Nielsen HL. et al. Evaluation of aspirin response by Multiplate whole blood aggregometry and light transmission aggregometry. Platelets 2009; 20: 415-420.
- 33 Malinin A, Spergling M, Muhlestein B. et al. Assessing aspirin responsiveness in subjects with multiple risk factors for vascular disease with a rapid platelet function analyzer. Blood Coagul Fibrinolysis 2004; 15: 295-301.
- 34 Karha J, Rajagopal V, Kottke-Marchant K. et al. Lack of effect of enteric coating on aspirin-induced inhibition of platelet aggregation in healthy volunteers. Am Heart J 2006; 151: 976e7-11.
- 35 Paniccia R, Antonucci E, Gori AM. et al. Comparison of different methods to evaluate the effect of aspirin on platelet function in high-risk patients with ischemic heart disease receiving dual antiplatelet treatment. Am J Clin Pathol 2007; 128: 143-149.
- 36 Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 01: 307-310.
- 37 Blais N, Pharand C, Lordkipanidze M. et al. Response to aspirin in healthy individuals. Cross-comparison of light transmission aggregometry, VerifyNow system, platelet count drop, thromboelastography (TEG) and urinary 11-dehydrothromboxane B(2). Thromb Haemost 2009; 102: 404-411.
- 38 Watala C, Golanski J, Pluta J. et al. Reduced sensitivity of platelets from type 2 diabetic patients to acetylsalicylic acid (aspirin)-its relation to metabolic control. Thromb Res 2004; 113: 101-113.
- 39 Perneby C, Wallen NH, Rooney C. et al. Dose- and time-dependent antiplatelet effects of aspirin. Thromb Haemost 2006; 95: 652-658.
- 40 Catella F, FitzGerald GA. Paired analysis of urinary thromboxane B2 metabolites in humans. Thromb Res 1987; 47: 647-656.
- 41 Cattaneo M. Aspirin and clopidogrel: efficacy, safety, and the issue of drug resistance. Arterioscler Thromb Vasc Biol 2004; 24: 1980-1987.
- 42 Michelson AD, Cattaneo M, Eikelboom JW. et al. Aspirin resistance: position paper of the Working Group on Aspirin Resistance. J Thromb Haemost 2005; 03: 1309-1311.
- 43 Frelinger AL, Li Y, Linden MD. et al. Aspirin ‘resistance‘: role of pre-existent platelet reactivity and correlation between tests. J Thromb Haemost 2008; 06: 2035-2044.
- 44 Kuliczkowski W, Witkowski A, Polonski L. et al. Interindividual variability in the response to oral antiplatelet drugs: a position paper of the Working Group on antiplatelet drugs resistance appointed by the Section of Cardiovascular Interventions of the Polish Cardiac Society, endorsed by the Working Group on Thrombosis of the European Society of Cardiology. Eur Heart J 2009; 30: 426-435.
- 45 Wallen NH, Ladjevardi M, Albert J. et al. Influence of different anticoagulants on platelet aggregation in whole blood; a comparison between citrate, low molecular mass heparin and hirudin. Thromb Res 1997; 87: 151-157.
- 46 Sibbing D, Braun S, Jawansky S. et al. Assessment of ADP-induced platelet aggregation with light transmission aggregometry and multiple electrode platelet aggregometry before and after clopidogrel treatment. Thromb Haemost 2008; 99: 121-126.
- 47 Würtz M, Grove EL, Kristensen SD. et al. The antiplatelet effect of aspirin is reduced by proton pump inhibitors in patients with coronary artery disease. Heart 2010; 96: 368-371.