Skip to main content

Advertisement

SpringerLink
Log in

Measurement of platelet reactivity of patients with cardiovascular disease on-treatment with acetyl salicylic acid: a prospective study

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

An Erratum to this article was published on 05 July 2011

Abstract

Acetyl salicylic acid (ASA) and clopidogrel are extensively used in the prevention of cardiovascular disease. However, the responsiveness to ASA treatment may vary among individuals. This study was conducted to investigate the profile and prevalence of ASA resistance in cardiac patients. From August 2007 to August 2008, a total of 282 cardiac patients were enrolled. Two study groups were identified: patients taking 100 mg ASA daily but without clopidogrel, and patients taking both 100 mg ASA and 75 mg clopidogrel daily. Platelet function was determined with the Multiplate analyzer to determine platelet responsiveness. Salicylate blood level was measured for all patients on ASA. Seventy-three patients (26%) were determined to be nonresponsive to ASA, and 45 patients (16%) were partially responsive, whereas 164 patients (58.2%) were responsive to ASA. Myocardial infarction and coronary obstruction were both strongly associated with ASA nonresponsiveness (p < 0.001). ASA resistance occurred more in female patients (p = 0.002). The salicylate blood level was found to be low in ASA-resistant patients (35.33 ± 50.22 mg/l) and higher in sensitive patients (54.26 ± 18.7 mg/l; p < 0.001). Quantitative assessment of platelet functions is predictive of ASA treatment failure in individual patients. Dual antiplatelet treatment with clopidogrel and ASA was found to have greater inhibitory effects on platelet aggregation than either agent alone. Non-adherence may be a significant mediator of poor outcome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Iwasaki K, Matsumoto T, Aono H, Furukawa H, Nagamachi K, Samukawa M (2010) Distribution of coronary atherosclerosis in patients with coronary artery disease. Heart Vessels 25:14–18

    Article  PubMed  Google Scholar 

  2. Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O’Donnell C, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y (2007) for the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 115:69–171

    Article  Google Scholar 

  3. Tseeng S, Arora R (2008) Aspirin resistance: biological and clinical implications. J Cardiovasc Pharmacol 13(1):5–12

    Article  CAS  Google Scholar 

  4. Matsuura K, Imamaki M, Ishida A, Shimura H, Miyazaki M (2009) The effect of preoperative aspirin administration on postoperative level of von Willebrand factor in off-pump coronary artery bypass surgery. Heart Vessels 24:169–174

    Article  PubMed  Google Scholar 

  5. Harrison P, Segal H, Silver L, Anila S, Cuthbertson F, Peter M (2008) Lack of reproducibility of assessment of aspirin responsiveness by optical aggregometry and two platelet function tests. Platelets 19(2):119–124

    Article  PubMed  CAS  Google Scholar 

  6. Steinhubl SR, Charnigo R, Moliterno DJ (2005) Resistance to antiplatelet resistance. J Am Coll Cardiol 45:1757–1758

    Article  PubMed  Google Scholar 

  7. Shantsila E, Lip GY (2008) ‘Aspirin resistance’ or treatment non-compliance: which is to blame for cardiovascular complications? J Transl Med 6:47–50

    Article  PubMed  Google Scholar 

  8. Mason P, Jacobs A, Freedman J (2005) Aspirin resistance and atherothrombotic disease. J Am Coll Cardiol 46:986–993

    Article  PubMed  CAS  Google Scholar 

  9. Michelson AD, Frelinger AL 3rd, Furman MI (2006) Current options in platelet function testing. Am J Cardiol 98(10):4–10

    Article  Google Scholar 

  10. Mueller TH, Dieplinger B, Poelz W, Haltmayer M (2009) Utility of the PFA-100 instrument and the novel multiplate analyzer for the assessment of aspirin and clopidogrel effects on platelet function in patients with cardiovascular disease. Clin Appl Thromb Hemost 15(6):652–659

    Article  PubMed  CAS  Google Scholar 

  11. Gurbel PA, Tantry US (2007) Clopidogrel resistance? Thromb Res 120(3):311–321

    Article  PubMed  CAS  Google Scholar 

  12. Haubelt H, Anders C, Hellstern P (2005) Can platelet function tests predict the clinical efficacy of aspirin? Semin Thromb Hemost 31:404–410

    Article  PubMed  CAS  Google Scholar 

  13. Michelson AD, Cattaneo M, Eikelboom JW, Gurbel P, Kottke-Marchant K, Kunicki TJ, Pulcinelli FM, Cerletti C, Rao AK (2005) Aspirin resistance: position paper of the Working Group on Aspirin Resistance. J Thromb Haemost 3(6):1309–1311

    Article  PubMed  CAS  Google Scholar 

  14. Calatzis A, Wittwer M, Krueger B (2004) A new approach to platelet function analysis in whole blood—the Multiplate analyzer. Platelets 15:485–486

    Google Scholar 

  15. Mueller TH, Dieplinger B, Poelz W, Calatzis A, Meinhard H (2007) Utility of whole blood impedance aggregometry for the assessment of clopidogrel action using the novel Multiplateanalyzer—comparison with two flow cytometric methods. Thromb Res 121:249–258

    Article  PubMed  CAS  Google Scholar 

  16. Toth O, Calatzis A, Penz S (2006) Multiple electrode aggregometry: a new device to measure platelet aggregation in whole blood. Thromb Haemost 96:781–788

    PubMed  CAS  Google Scholar 

  17. Seyfert UT, Haubelt H, Vogt A (2007) Variables influencing Multiplate (TM) whole blood impedance platelet aggregometry and turbidimetric platelet aggregation in healthy individuals. Platelets 18:199–206

    Article  PubMed  CAS  Google Scholar 

  18. Gurbel PA, Bliden KP, DiChiara J, Newcomer J, Weng W, Neerchal NK, Gesheff T, Chaganti SK, Etherington A, Tantry US (2007) Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study. Circulation 115(25):3156–3164

    Google Scholar 

  19. Weber AA, Przytulski B, Schanz A, Hohlfeld T, Schror K (2002) Towards a definition of aspirin resistance: a typological approach. Platelets 13:37–40

    Article  PubMed  CAS  Google Scholar 

  20. Tantry US, Bliden KP, Gurbel PA (2005) Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation. J Am Coll Cardiol 46:1705–1709

    Article  PubMed  CAS  Google Scholar 

  21. Mueller MR, Salat A, Stangl P (1997) Variable platelet response to low dose ASA and the risk of limb deterioration in patients submitted to peripheral arterial angioplasty. Thromb Haemost 78(3):1003–1007

    PubMed  CAS  Google Scholar 

  22. Berrouschot J, Schwetlick B, von Twickel G, Fischer C, Uhlemann H, Siegemund T, Siegemund A, Roessler A (2006) Aspirin resistance in secondary stroke prevention. Acta Neurol Scand 113(1):31–35

    Article  PubMed  CAS  Google Scholar 

  23. Gengo F, Rainka M, Robson M, Gengo M, Forrest A, Hourihane M, Bates V (2008) Prevalence of platelet nonresponsiveness to aspirin in patients treated for secondary stroke. J Clin Pharmacol 48:335–343

    Article  PubMed  CAS  Google Scholar 

  24. Buchanan MR, Brister SJ (1995) Individual variation in the effects of ASA on platelet function: implications for the use of ASA clinically. Can J Cardiol 11(3):221–227

    PubMed  CAS  Google Scholar 

  25. Gum P, Kottke-Marchant K, Poggio ED (1995) Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol 88:230–235

    Article  Google Scholar 

  26. Grundmann K, Jaschonek K, Kleine B, Dichgans J, Topka H (2003) Aspirin non-responder status in patients with recurrent cerebral ischemic attacks. J Neurol 250:63–66

    Article  PubMed  CAS  Google Scholar 

  27. Andersen K, Hurlen M, Arnesen H, Seljeflot I (2002) Aspirin non-responsiveness as measured by PFA-100 in patients with coronary artery disease. Thromb Res 108:37–42

    Article  PubMed  Google Scholar 

  28. Sane DC, McKee SA, Malinin AI, Serebruany V (2002) Frequency of aspirin resistance in patients with congestive heart failure treated with antecedent aspirin. Am J Cardiol 90:893–895

    Article  PubMed  CAS  Google Scholar 

  29. Grotemeyer KH, Scharafinski HW, Husstedt IW (1993) Two year follow-up of aspirin responder and aspirin nonresponder: a pilot study including 180 post stroke patients. Thromb Res 71(5):397–403

    Article  PubMed  CAS  Google Scholar 

  30. Eikelboom JW, Hirsh J, Weitz JI, Johnston M, Yi Q, Yusuf S (2002) Aspirin-resistant thromboxane biosynthesis and the risk of myocardial risk for cardiovascular events. Circulation 105:1650–1655

    Article  PubMed  CAS  Google Scholar 

  31. Helgason CM, Tortorice KL, Winkler SR, Penney DW, Schuler JJ, McClelland TJ, Brace LD (1993) Aspirin response and failure in cerebral infarction. Stroke 24:345–350

    Article  PubMed  CAS  Google Scholar 

  32. Hovens MM, Snoep JD, Eikenboom JC, van der Bom JG, Mertens BJ, Huisman MV (2007) Prevalence of persistent platelet reactivity despite use of aspirin: a systematic review. Am Heart J 153:175–181

    Article  PubMed  CAS  Google Scholar 

  33. Pamukcu B, Oflaz H, Nisanci Y (2005) The role of platelet glycoprotein IIIa polymorphism in the high prevalence of in vitro aspirin resistance in patients with intracoronary stent restenosis. Am Heart J 149(4):675–680

    Article  PubMed  CAS  Google Scholar 

  34. Liu Z, Yang Y, Mao Y, Wang X, Wang J, Huo Y (2008) Profile and prevalence of aspirin resistance in patients with metabolic syndrome. J Geriatr Cardiol 5(1):7–10

    CAS  Google Scholar 

  35. Tarján J, Salamon A, Jáger R, Poór F, Barczi V, Dinnyés J, Hamvas J, Kinczel A, Pál A, Blaskó G (1999) The rate of acetylsalicylic acid non-respondents among patients hospitalized for acute coronary disease, previously undergoing secondary salicylic acid prophylaxis. Orv Hetil 140(42):2339–2343

    PubMed  Google Scholar 

  36. Schwartz KA, Schwartz DE, Ghosheh K, Reeves MJ, Barber K, Defranco A (2005) Compliance as a critical consideration in patients who appear to be resistant to aspirin after healing of myocardial infarction. Am J Cardiol 95:973–975

    Article  PubMed  CAS  Google Scholar 

  37. Zimmermann N, Wenk A, Kim U (2003) Functional and biochemical evaluation of platelet aspirin resistance after coronary artery bypass surgery. Circulation 108:542–547

    Article  PubMed  CAS  Google Scholar 

  38. Cotter G, Shemesh E, Zehavi M (2004) Lack of aspirin effect: aspirin resistance or resistance to taking aspirin? Am Heart J 147:293–300

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the deanship with scientific research grant number: 1024.

Author information

Authors and Affiliations

  1. Department of Medicine, University of Jordan, Amman, Jordan

    Abdalla Awidi, Akram Saleh, Mohammed Abu-Fara & Rinad Nabulsi

  2. Thrombosis Hemostasis Laboratory, Jordan University Hospital, Queen Rania Al Abdallah Street, Amman, Jordan

    Abdalla Awidi, Manar Dweik & Baraah Kailani

  3. Department of Medical Statistics and Epidemiology, Hamad Medical Corporation, Hamad General Hospital, Doha, Qatar

    Abdulbari Bener

  4. Department of Public Health and Medical Education, Weill Cornell Medical College, New York, USA

    Abdulbari Bener

Authors
  1. Abdalla Awidi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akram Saleh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manar Dweik
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Baraah Kailani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammed Abu-Fara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rinad Nabulsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Abdulbari Bener
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abdalla Awidi.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00380-011-0171-z

Rights and permissions

Reprints and permissions

About this article

Cite this article

Awidi, A., Saleh, A., Dweik, M. et al. Measurement of platelet reactivity of patients with cardiovascular disease on-treatment with acetyl salicylic acid: a prospective study. Heart Vessels 26, 516–522 (2011). https://doi.org/10.1007/s00380-010-0086-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-010-0086-0

Keywords

Search

Navigation