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Semin Thromb Hemost 2012; 38(02): 200-212
DOI: 10.1055/s-0032-1301417
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

High Platelet Reactivity and Antiplatelet Therapy Resistance

Matthew D. Linden
1   School of Medical Sciences and Health Innovations Research Institute, RMIT University, Melbourne, Australia
2   Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia
,
Huyen Tran
3   Australian Centre for Blood Diseases, Monash University, Melbourne, Australia
,
Robyn Woods
2   Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia
,
Andrew Tonkin
2   Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia
› Author Affiliations
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Publication History

Publication Date:
16 February 2012 (online)

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Abstract

The term resistance has been applied to interindividual variability in platelet reactivity during antiplatelet therapy or to thrombosis despite appropriate therapy. In particular “aspirin resistance” and “clopidogrel resistance” have been the subject of intense investigation for their association with poor cardiovascular outcomes. Several mechanisms have been investigated including resistance arising from poor bioavailability, especially in clopidogrel therapy as resulting from a loss of function variant in hepatic metabolism required for prodrug activation. A limitation of studies linking on-treatment reactivity and clinical outcome is that they have been performed in high-risk patients with recent atherothrombotic disease. On-treatment platelet reactivity correlates with acuity of recent atherothrombosis, and variability in pretreatment platelet function predicts on-treatment platelet function for both aspirin and clopidogrel. It is therefore likely that high on-treatment platelet function at the time of testing may often result from underlying platelet hyperreactivity related to acute atherothrombosis, rather than true pharmacological resistance. The association of high on-treatment platelet reactivity with poor clinical outcomes may therefore be attributed to variability in underlying burden of disease instead of, or in addition to, pharmacological resistance to antiplatelet therapy.

Keywords

aspirin resistance - clopidogrel resistance - platelet hyperreactivity - cardiovascular disease - antiplatelet therapy