Published Online
on December 16, 2004

A more recent version of this article appeared on February 1, 2005

This Article Full Text (PDF) All Versions of this Article: 36/2/276    most recent 01.STR.0000151362.65339.f9v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gonzalez-Conejero, R. Articles by Vicente, V. Search for Related Content PubMed PubMed Citation Articles by Gonzalez-Conejero, R. Articles by Vicente, V. Related Collections Aggregation Platelet function inhibitors Platelets Other Research

Submitted on August 9, 2004
Revised on October 5, 2004
Accepted on October 28, 2004

Biological Assessment of Aspirin Efficacy on Healthy Individuals. Heterogeneous Response or Aspirin Failure?

Rocio Gonzalez-Conejero PhD^*; Jose Rivera PhD; Javier Corral PhD; Carmen Acuña DSc; Jose A. Guerrero DSc; and Vincente Vicente PhD, MD

From the University of Murcia (R.G.-C., J.R., J.C.), Centro Regional de Hemodonación; and Hospital Morales Meseguer (C.A., J.A.G., V.V.), Centro Regional de Hemodonación, Murcia, Spain.

^* To whom correspondence should be addressed. E-mail: rocio.gonzalez{at}carm.es.

Background and Purpose--The widespread use of aspirin requires clarification of the aspirin resistance phenomenon. Most studies on this field are focused on patients which may affect the action of aspirin.

Methods--We evaluated the biological efficacy of aspirin in healthy subjects.

Results--Agonist-induced platelet aggregation was fully abrogated by 100 mg of aspirin in all individuals. By contrast, with the platelet function analyzer-100 device, 33.3% of the subjects displayed no response. This failure was overcome by 500 mg or by in vitro treatment of blood with 30 µmol/L acetylsalicylic acid. Intake of 100 mg of aspirin efficiently reduced by 75% the level of 11-dehydro thromboxane B₂ (11-dTxB₂) in all cases. However, variability on the pre-aspirin level (range 72.4 to 625.9 ng/mmol creatinine) led to substantial differences in the residual amount of the metabolite between subjects treated with aspirin (range 12.9 to 118.0 ng/mmol creatinine). Finally, there was no influence of platelet glycoprotein IIb/IIIa (Pro33Leu), platelet glycoprotein Ia/IIa, (C807T), and FXIII (Val34Leu) polymorphisms on the efficacy of aspirin. However, the cyclooxygenase (Cox)-1 50T allele associated with higher level of 11-dTxB₂, both before and after aspirin. Moreover, the Cox-2 -765C variant displayed a slightly higher reduction in 11-dTxB₂ level on treatment with aspirin.

Conclusions--Our findings suggest that full resistance of healthy subjects to aspirin is rather unlikely. However, differences in aspirin absorption, or pharmacokinetic, or other unrecognized factors may lead to lack of effect of low dose of aspirin in some subjects when using tests like platelet function analyzer-100. Whether Cox polymorphisms are thrombotic risk factor for patients under aspirin will require further research.

Key words: aspirin • platelet function tests • polymorphisms

This article has been cited by other articles:

				J. F. Meschia Pharmacogenetics and Stroke Stroke, November 1, 2009; 40(11): 3641 - 3645. [Abstract] [Full Text] [PDF]

				F. Marin, R. Gonzalez-Conejero, P. Capranzano, T. A. Bass, V. Roldan, and D. J. Angiolillo Pharmacogenetics in cardiovascular antithrombotic therapy. J. Am. Coll. Cardiol., September 15, 2009; 54(12): 1041 - 1057. [Abstract] [Full Text] [PDF]

				A R Muir, M F McMullin, C Patterson, and P P McKeown Assessment of aspirin resistance varies on a temporal basis in patients with ischaemic heart disease Heart, August 1, 2009; 95(15): 1225 - 1229. [Abstract] [Full Text] [PDF]

				W. Kuliczkowski, A. Witkowski, L. Polonski, C. Watala, K. Filipiak, A. Budaj, J. Golanski, D. Sitkiewicz, J. Pregowski, J. Gorski, 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., February 2, 2009; 30(4): 426 - 435. [Abstract] [Full Text] [PDF]

				O. M. Akay, Z. Canturk, E. Akin, C. Bal, and Z. Gulbas Aspirin-Resistance Frequency: A Prospective Study in 280 Healthy Turkish Volunteers Clinical and Applied Thrombosis/Hemostasis, February 1, 2009; 15(1): 98 - 102. [Abstract] [PDF]

				B. S. Karon, A. Wockenfus, R. Scott, S. J. Hartman, J. P. McConnell, P. J. Santrach, and A. S. Jaffe Aspirin Responsiveness in Healthy Volunteers Measured with Multiple Assay Platforms Clin. Chem., June 1, 2008; 54(6): 1060 - 1065. [Abstract] [Full Text] [PDF]

				A. Y. Gasparyan, T. Watson, and G. Y.H. Lip The Role of Aspirin in Cardiovascular Prevention: Implications of Aspirin Resistance J. Am. Coll. Cardiol., May 13, 2008; 51(19): 1829 - 1843. [Abstract] [Full Text] [PDF]

				S. Tseeng and R. Arora Aspirin Resistance: Biological and Clinical Implications Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2008; 13(1): 5 - 12. [Abstract] [PDF]

				M. Lordkipanidze, C. Pharand, E. Schampaert, J. Turgeon, D. A. Palisaitis, and J. G. Diodati 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., July 2, 2007; 28(14): 1702 - 1708. [Abstract] [Full Text] [PDF]

				M. Cattaneo Laboratory detection of 'aspirin resistance': what test should we use (if any)? Eur. Heart J., July 2, 2007; 28(14): 1673 - 1675. [Full Text] [PDF]

				P. A. Gurbel, K. P. Bliden, J. DiChiara, J. Newcomer, W. Weng, N. K. Neerchal, T. Gesheff, S. K. Chaganti, A. Etherington, and U. S. Tantry Evaluation of Dose-Related Effects of Aspirin on Platelet Function: Results From the Aspirin-Induced Platelet Effect (ASPECT) Study Circulation, June 26, 2007; 115(25): 3156 - 3164. [Abstract] [Full Text] [PDF]

				N. Faraday, L. R. Yanek, R. Mathias, J. E. Herrera-Galeano, D. Vaidya, T. F. Moy, M. D. Fallin, A. F. Wilson, P. F. Bray, L. C. Becker, et al. Heritability of Platelet Responsiveness to Aspirin in Activation Pathways Directly and Indirectly Related to Cyclooxygenase-1 Circulation, May 15, 2007; 115(19): 2490 - 2496. [Abstract] [Full Text] [PDF]

				A. Undas, K. E. Brummel-Ziedins, and K. G. Mann Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions Blood, March 15, 2007; 109(6): 2285 - 2292. [Abstract] [Full Text] [PDF]