Persistent production of platelet thromboxane A2 in patients chronically treated with aspirin.
BACKGROUND
Patients treated with aspirin may have a reduced sensitivity to its antiplatelet effect. The mechanism accounting for such a reduced sensitivity might involve an impaired interaction of aspirin with cyclooxygenase-1 (COX)-1.


OBJECTIVE
We sought to investigate whether platelets from patients under chronic treatment with aspirin still produce TxA2 and whether there is any relationship between the eventual persistent TxA2 formation and platelet aggregation. Finally, whether platelet-derived TxA2 can be inhibited by in vitro addition of aspirin.


METHODS
Collagen-induced platelet aggregation and thromboxane-A2 (TxA2) were measured in 196 patients treated with aspirin (100-330 mg day(-1)) because of previous vascular events or presence of risk factors of atherosclerosis.


RESULTS
Collagen-induced TxA2 production of the entire cohort was 128.7 +/- 21.6 pg 10(-8) cells, and was significantly correlated with platelet aggregation (Spearman's correlation coefficient = 0.44; P < 0.0001). Patients in the highest quartile of TxA2 showed higher platelet response to collagen (P < 0.0001) when compared with those in the lowest quartile. In a subgroup of 96 patients, platelets were treated in vitro with a TxA2 receptor antagonist (13-azaprostanoic acid) or aspirin before stimulation with collagen. 13-APA acid significantly inhibited platelet aggregation. Aspirin reduced (-72.9%) TxA2 production in patients with TxA2 values above the median but it was ineffective in those with TxA2 values below the median.


CONCLUSIONS
In some patients chronically treated with aspirin platelet production of TxA2 may persist and account for enhanced platelet aggregation. Incomplete inhibition of COX-1 seems to be implicated in persistent TxA2 production.
Pulcinelli
F M
FM
Department of Experimental Medicine and Pathology, University La Sapienza, Roma 00161, Italy. fabio.pulcinelli@uniroma1.it
Riondino
S
S
Celestini
A
A
Pignatelli
P
P
Trifirò
E
E
Di Renzo
L
L
Violi
F
F
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy; D003094:Collagen; D051545:Cyclooxygenase 1 / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology
D013928:Thromboxane A2; D003094:Collagen; D051545:Cyclooxygenase 1; D001241:Aspirin