Thromboxane A2 Generation, in the Absence of Platelet COX-1 Activity, in Patients With and Without Atherothrombotic Myocardial Infarction

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 >= 1 mmol/L arachidonic acid. Median urine 11-dehydro-TxB(2) was no different in those with and without a diagnosis of atherothrombotic MI (325 vs. 311 pg/mg creatinine, P=0.59 via polyclonal ELISA) and (312 vs. 244 pg/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. 606 pg/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.