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Licensed Unlicensed Requires Authentication Published by De Gruyter November 12, 2015

Platelet aggregation in response to ADP is highly variable in normal donors and patients on anti-platelet medication

  • Eimear Dunne ORCID logo , Karl Egan , Siobhán McFadden , David Foley and Dermot Kenny EMAIL logo

Abstract

Background: P2Y12 inhibitors are indicated in patients following percutaneous coronary intervention. Several studies have demonstrated that high on treatment platelet reactivity is correlated with outcomes yet prospective studies of guided therapy have failed to show benefit. There is a paucity of studies on the platelet aggregation response to ADP before P2Y12 therapy is started. The aim of this study was to characterize platelet responses to 20 μM ADP by light transmission aggregometry (LTA) in a homogenous population.

Methods: Platelet aggregation was assessed in 201 patients on dual antiplatelet therapy, 98 patients on aspirin alone and 47 normal, healthy volunteers free from anti-platelet medication.

Results: Consensus guidelines suggest that a platelet aggregation response in response to the agonist ADP of <57% is an adequate therapeutic response to P2Y12 inhibition. Seven healthy donors and 38 patients taking aspirin only had aggregation responses below 57%.

Conclusions: The results of our study demonstrate that 15% of normal donors and 38% of patients taking aspirin only would be classified as having a therapeutic response to P2Y12 inhibition using current guidelines.


Corresponding author: Dermot Kenny, Cardiovascular Biology and Clinical Research Centre, Royal College of Surgeons in Ireland, 123 St Stephen’s Green, Dublin 2, Ireland, Phone: +353 (1) 4022358, Fax: +353 (1) 4022453, E-mail: ; and Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland

Acknowledgments

This study was supported by Science Foundation Ireland under Grant No. 10/CE3/B1821. No industry sponsorship applies.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Siller-Matula JM, Trenk D, Schrör K, Gawaz M, Kristensen SD, Storey RF, et al. Response variability to P2Y12 receptor inhibitors: expectations and reality. JACC Cardiovasc Interv 2013;6:1111–28.10.1016/j.jcin.2013.06.011Search in Google Scholar PubMed

2. Cuisset T, Grosdidier C, Loundou AD, Quilici J, Loosveld M, Camoin L, et al. Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study (predictor of bleedings with antiplatelet drugs). JACC Cardiovasc Interv 2013;6:854–63.10.1093/eurheartj/eht310.4528Search in Google Scholar

3. Villacorta AS, Villacorta Junior H, Batista MJ, Gomes RV, Macedo LA, Helmuth B, et al. High on-treatment platelet reactivity predicts cardiac events in patients with drug-eluting stents. Arq Bras Cardiol 2013;100:221–8.10.5935/abc.20130044Search in Google Scholar PubMed

4. Cattaneo M. High on-treatment platelet reactivity–definition and measurement. Thromb Haemost 2013;109:792–8.10.1160/TH12-10-0758Search in Google Scholar PubMed

5. Saia F, Marino M, Campo G, Valgimigli M, Guastaroba P, Taglieri N, et al. Incidence and outcome of high on-treatment platelet reactivity in patients with non-ST elevation acute coronary syndromes undergoing percutaneous coronary intervention (from the VIP [VerifyNow and Inhibition of Platelet Reactivity] study). Am J Cardiol 2013;112:792–8.10.1016/j.amjcard.2013.05.010Search in Google Scholar PubMed

6. Samara WM, Bliden KP, Tantry US, Gurbel PA. The difference between clopidogrel responsiveness and posttreatment platelet reactivity. Thromb Res 2005;115:89–94.10.1016/j.thromres.2004.07.002Search in Google Scholar PubMed

7. Cattaneo M. Potential clinical utility of genetic and platelet function tests in patients on treatment with clopidogrel. J Cardiovasc Med 2013;14 Suppl 1:S16–21.10.2459/JCM.0b013e328364bd3aSearch in Google Scholar PubMed

8. Sousa-Uva M, Storey R, Huber K, Falk V, Leite-Moreira AF, Amour J, et al. Expert position paper on the management of antiplatelet therapy in patients undergoing coronary artery bypass graft surgery. Eur Heart J 2014;35:1510–4.10.1093/eurheartj/ehu158Search in Google Scholar PubMed PubMed Central

9. Pulcinelli FM, Pignatelli P, Celestini A, Riondino S, Gazzaniga PP, Violi F. Inhibition of platelet aggregation by aspirin progressively decreases in long-term treated patients. J Am Coll Cardiol 2004;43:979–84.10.1016/j.jacc.2003.08.062Search in Google Scholar PubMed

10. Santilli F, Rocca B, De Cristofaro R, Lattanzio S, Pietrangelo L, Habib A, et al. Platelet cyclooxygenase inhibition by low-dose aspirin is not reflected consistently by platelet function assays: implications for aspirin “resistance”. J Am Coll Cardiol 2009;53:667–77.10.1016/j.jacc.2008.10.047Search in Google Scholar PubMed

11. Miller CH, Rice AS, Garrett K, Stein SF. Gender, race and diet affect platelet function tests in normal subjects, contributing to a high rate of abnormal results. Br J Haematol 2014;165:842–53.10.1111/bjh.12827Search in Google Scholar PubMed PubMed Central

12. Price MJ, Nayak KR, Barker CM, Kandzari DE, Teirstein PS. Predictors of heightened platelet reactivity despite dual-antiplatelet therapy in patients undergoing percutaneous coronary intervention. Am J Cardiol 2009;103:1339–43.10.1016/j.amjcard.2009.01.341Search in Google Scholar PubMed

13. Cattaneo M, Cerletti C, Harrison P, Hayward CP, Kenny D, Nugent D, et al. Recommendations for the standardization of light transmission aggregometry: a consensus of the working party from the platelet physiology subcommittee of SSC/ISTH. J Thromb Haemost 2013;11:1183–9.10.1111/jth.12231Search in Google Scholar PubMed

14. Bewick V, Cheek L, Ball J. Statistics review 13: receiver operating characteristic curves. Crit Care 2004;8:508–12.10.1186/cc3000Search in Google Scholar PubMed PubMed Central

15. Ono T, Kaikita K, Hokimoto S, Iwashita S, Yamamoto K, Miyazaki Y, et al. Determination of cut-off levels for on-clopidogrel platelet aggregation based on functional CYP2C19 gene variants in patients undergoing elective percutaneous coronary intervention. Thromb Res 2011;128:e130–6.10.1016/j.thromres.2011.07.028Search in Google Scholar PubMed

16. Jaitner J, Stegherr J, Morath T, Braun S, Bernlochner I, Schomig A, et al. Stability of the high on-treatment platelet reactivity phenotype over time in clopidogrel-treated patients. Thromb Haemost 2011;105:107–12.10.1160/TH10-07-0440Search in Google Scholar PubMed

17. Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, Ruven HJ, Bal ET, et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA 2010;303:754–62.10.1001/jama.2010.181Search in Google Scholar PubMed

Received: 2015-8-19
Accepted: 2015-10-7
Published Online: 2015-11-12
Published in Print: 2016-7-1

©2016 by De Gruyter

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