Persistent production of thromboxane (Tx)A2 is the most likely cause of aspirin resistance and even small increases can trigger platelet activation, the Italian researchers state in the journal Thrombosis Research.
They add that TxA2 can be generated by both COX isoforms, COX-1 and COX-2, but that the source of residual TxA2 remains largely unknown.
To investigate whether persistent TxA2 production was at least partially dependent on an aspirin-insensitive platelet COX-2 enzymatic pathway, the team studied 100 consecutive patients receiving chronic aspirin treatment of 100 to 160 mg per day.
All patients had detectable salicylate levels and reduced serum and arachidonic acid (AA)-induced TxA2 generation, indicating that they were compliant with therapy.
Whereas COX-1 expression was observed in all patients, COX-2 expression was identified in 46% of the group, albeit at low levels.
However, in vitro studies performed on platelets from 10 patients who were positive for COX-2 and had TxA2 levels over the median indicated that the portion of TxA2 ascribable to COX-2 activation was less than 2%.
"Our data demonstrate that the inter-individual variability of platelet sensitivity to aspirin is a phenomenon that is due to a reduced efficacy of aspirin on platelet COX-1," say Fabio Pulcinelli ("Sapienza" University, Rome, Italy) and colleagues.
"Even in patients expressing platelet COX-2 the amount of COX-2 dependent TxA2 is minimal, thus rendering the combined use of COX-2 inhibitors and aspirin useless or harmful due to inhibition of protective endothelial prostanoids generated by COX-2."
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删除 宫健 (2008-7-24 16:51:49, 评分: 5 )