Background: Aspirin’s therapeutic action is via inhibition of platelet cyclooxygenase 1 (COX-1) thromboxane A
2 (TxA
2) production. The aim of this study was to evaluate TxA
2 production, in the absence of platelet COX-1 activity, in coronary atherosclerotic heart disease patients with and without atherothrombotic myocardial infarction (MI).
Methods and Results: TxA
2 production, in the absence of platelet COX-1 activity, was evaluated in 44 patients taking aspirin on 3 commercially available assays that detect metabolites of TxA
2 in the urine. Two assays measure urine 11-dehydro-thromboxane B
2 (TxB
2) alone and 1 measures urine 11-dehydro-TxB
2 plus 11-dehydro-2,3-dinor-TxB
2. Platelet COX-1 inhibition was confirmed on <10% platelet aggregation in response to ≥1mmol/L arachidonic acid. Median urine 11-dehydro-TxB
2 was no different in those with and without a diagnosis of atherothrombotic MI (325 vs. 311pg/mg creatinine, P=0.59 via polyclonal ELISA) and (312 vs. 244pg/mg creatinine, P=0.11 via LC-MS/MS). Median urine 11-dehydro-TxB
2 plus 11-dehydro-2,3-dinor-TxB
2, however, was higher in those with vs. those without a diagnosis of atherothrombotic MI (1,035 vs. 606pg/mg creatinine, P=0.03 via monoclonal ELISA).
Conclusions: Differences in TxA
2 production, in the absence of platelet COX-1 activity, between those with vs. without atherothrombotic MI were not observed when TxA
2 generation was assessed on 11-dehydro-TxB
2 production alone (polyclonal ELISA or LC-MS/MS), but differences were observed when TxA
2 generation was assessed using 11-dehydro-TxB
2 plus 11-dehydro-2,3-dinor-TxB
2 (monoclonal ELISA). These findings highlight important differences between different commercially available assays for TxA
2 generation and suggest that 11-dehydro-2,3-dinor-TxB
2 may be critical to the biology of atherothrombosis. (
Circ J 2013;
77: 2786–2792)
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