Lack of biological relevance of platelet cyclooxygenase-2 dependent thromboxane A2 production.
BACKGROUND
There is emerging evidence of a considerable variability of the impact of aspirin on clinical outcome and laboratory findings. Persistent TxA2 production seems to be the most likely reason. Aim of this study was to determine whether the mechanism responsible for TxA2 persistent production is, at least partially, dependent upon aspirin-insensitive platelet COX-2 enzymatic pathway.


RESULTS
In 100 consecutive patients, under chronic aspirin anti-platelet treatment (100-160 mg/day) selected on the basis of detectable plasma salicylate levels, serum and Arachidonic Acid (AA)-induced platelet TxA2 production, immunoblot analysis of platelet COX-1/COX-2 expression and COX-2 activity were studied. Immunoblot revealed COX-2 expression in 46% patients, in an amount that was markedly lower than COX-1. In 10 COX-2 positive patients with TxA2 levels over the median, AA-induced TxA2 production performed in vitro in the presence of the COX-2 inhibitor CAY10404 and aspirin demonstrated that COX-2 dependent TxA2 production is less than 2%.


CONCLUSIONS
Our data demonstrate that the inter-individual variability of platelet sensitivity to aspirin is due to a reduced efficacy of aspirin on platelet COX-1 despite ascertained patient compliance. We suggest that serum TxA2 assay might be performed in future clinical studies to improve our knowledge on the residual TxA2 production in aspirin-treated patients.
Riondino
Silvia
S
Department of Experimental Medicine, "Sapienza" University, Italy.
Trifirò
Elisabetta
E
Principessa
Lorenzo
L
Mascioletti
Silvia
S
Di Renzo
Livia
L
Gaudio
Carlo
C
Biasucci
Luigi M
LM
Crea
Filippo
F
Pulcinelli
Fabio M
FM
D000368:Aged; D000465:Algorithms; D001241:Aspirin / Q000008:administration & dosage* / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000517:prevention & control; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000502:physiology*; D005260:Female; D006405:Hematology / Q000379:methods* / Q000592:standards; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000097:blood; D013928:Thromboxane A2 / Q000378:metabolism*
D010975:Platelet Aggregation Inhibitors; D013928:Thromboxane A2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D001241:Aspirin