Aspirin Resistance: Does It Exist?

ABSTRACT

Aspirin irreversibly inhibits platelet cyclooxygenase-1 (COX-1). Aspirin sensitivity can be measured easily by its inhibition of arachidonic acid (AA) -induced platelet aggregation. Aspirin resistance has to be defined by its inability to inhibit COX-1. By using this definition, aspirin resistance very likely does not exist. A specific rapid laboratory test using either AA-induced platelet aggregation or AA-induced malondialdehyde production in platelet-rich plasma is needed to test aspirin sensitivity. The reports on so-called aspirin resistance are usually due to noncompliance of aspirin intake or consumption of inadequate doses of aspirin. In addition, data generated from using nonspecific platelet function tests have added confusion to this observed phenomenon of aspirin resistance.

KEYWORDS

Aspirin - aspirin resistance - aggregometry - laboratory testing - COX-1 - arachidonic acid - malondialdehyde

REFERENCES

• 1 Rao G HR. Aspirin resistance: a fact or a myth?.  Exp Clin Cardiol. 2005;  10 17-20
• 2 Rao G HR. Aspirin resistance: need for a specific and rapid assay.  World Heart J. 2006;  1 63-78
• 3 Pollack A. New York Times 2004. 
• 4 Roth J G, Caverley D C. Aspirin, platelets and thrombosis: theory and practice.  Blood. 1994;  83 885-898
• 5 Roth J G, Stanford N, Majerus P W. Acetylation of prostaglandin synthetase by aspirin.  Proc Natl Acad Sci USA. 1975;  72 3073-3076
• 6 Roth G J, Majerus P W. The mechanism of the effect of aspirin on human platelets.  J Clin Invest. 1975;  56 624-632
• 7 Smith J B, Ingerman C M, Silver M J. Malodialdehyde formation as an indicator of prostaglandin production by human platelets.  J Lab Clin Med. 1976;  13 167-172
• 8 Michiels J J, Abels J, Steketee J, van Vliet H HDM, Vuzevski V D. Erythromelalgia caused by platelet-mediated arteriolar inflammation and thrombosis in thrombocythemia.  Ann Intern Med. 1985;  102 466-471
• 9 Michiels J J, Zijlstra F J. Prostaglandin cyclooxygenase products but not thromboxane A2 are involved in the pathogenesis of erythromelalgia in thrombocythemia.  Mediators Inflamm. 1993;  2 385-389
• 10 Van Genderen P JJ, Lucas I S, van Strik R et al.. Erythromelalgia in essential thrombocythemia is characterized by platelet activation and endothelial cell damage but not by thrombin generation.  Thromb Haemost. 1996;  76 333-338
• 11 Van Genderen P JJ, Prins F, Michiels J J, Schrör K. Thromboxane-dependent platelet activation in vivo precedes arterial thrombosis in thrombocythaemia: a rationale for the use of low-dose aspirin as an antithrombotic agent.  Br J Haematol. 1999;  104 438-441
• 12 Michiels J J, Berneman Z, Schroyens W et al.. Platelet-mediated erythromelalgic, cerebral, ocular and coronary ischemic and thrombotic manifestations in patients with essential thrombocythemia and polycythemia vera. A distinct aspirin-responsive and coumadin resistant arterial thrombophilia.  Platelets. 2006;  17 528-544
• 13 Van Genderen P JJ, Mulder P GH, Waleboer M, van de Moesdijk D, Michiels J J. Prevention and treatment of thrombotic complications in essential thrombocythemia: efficacy and safety of aspirin.  Br J Haematol. 1997;  97 179-184
• 14 Landolfi R, Marchioli R, Kutti J et al.. Efficacy and safety of low-dose aspirin in polycythemia vera: results of the ECLAP trial.  N Engl J Med. 2004;  350 114-124
• 15 Michiels J J, Berneman Z, Schroyens W, Koudstaal P J, Lindemans J, van Vliet H HDM. Platelet-mediated thrombotic complications in patients with ET: reversal by aspirin, platelet reduction but not by coumadin.  Blood Cells Mol Dis. 2006;  36 199-205
• 16 Rao G HR, White J G. Epinephrine potentiation of arachidonate induced aggregation of cyclooxygenase deficient platelets.  Am J Hematol. 1981;  11 355-366
• 17 Swier P, Mohammad S F, Olsen D B, Kolff W J. A comparison of the antiplatelet effect of aspirin on human and bovine platelets.  ASAIO Trans. 1989;  35 205-208
• 18 Rao G HR, Ericson D G, Weiss D J, Park P G, White J G. Influence of aspirin and carbacyclin on bovine platelet function.  ASAIO J. 1992;  38 830-834
• 19 Rao G HR, Johnson J G, White J G. Ibuprofen protects platelet cyclooxygenase from irreversible inhibition by aspirin.  Arteriosclerosis. 1983;  3 384-388
• 20 Rao G HR, Johnson G J, White J G. Influence of epinephrine on the aggregation response of aspirin-treated platelets.  Prost Med. 1980;  5 45-48
• 21 Rao G HR, Escolar G, White J G. Epinephrine reverses the inhibitory influence of aspirin on platelet-vessel wall interactions.  Thromb Res. 1986;  44 65-74