Biological assessment of aspirin efficacy on healthy individuals: heterogeneous response or aspirin failure?
OBJECTIVE
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 mumol/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.
Gonzalez-Conejero
Rocio
R
University of Murcia, Centro Regional de Hemodonación, Ronda de Garay s/n, 30003, Murcia, Spain. rocio.gonzalez@carm.es
Rivera
Jose
J
Corral
Javier
J
Acuña
Carmen
C
Guerrero
Jose A
JA
Vicente
Vincente
V
D000042:Absorption; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000737:chemistry / Q000494:pharmacology*; D003404:Creatinine / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005176:Factor XIII / Q000737:chemistry; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D038982:Integrin alpha2beta1 / Q000737:chemistry; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D038982:Integrin alpha2beta1; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D005176:Factor XIII; D003404:Creatinine; D051546:Cyclooxygenase 2; D001241:Aspirin