Thromboxane A2 generation, in the absence of platelet COX-1 activity, in patients with and without atherothrombotic myocardial infarction

Andrew P. DeFilippis, Oluwasegun S. Oloyede, Efstathia Andrikopoulou, Amy K. Saenger, Joel M. Palachuvattil, Yetunde A. Fasoro, Eliseo Guallar, Roger S. Blumenthal, Thomas S. Kickler, Allan S. Jaffe, Gary Gerstenblith, Steven P. Schulman, Jeffrey J. Rade

Research output: Contribution to journalArticle

Abstract

Background: Aspirin's therapeutic action is via inhibition of platelet cyclooxygenase 1 (COX-1) thromboxane A2 (TxA2) production. The aim of this study was to evaluate TxA2 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: TxA2 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 TxA2 in the urine. Two assays measure urine 11-dehydro-thromboxane B2 (TxB2) alone and 1 measures urine 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor- TxB2. Platelet COX-1 inhibition was confirmed on <10% platelet aggregation in response to ≥1 mmol/L arachidonic acid. Median urine 11-dehydro-TxB2 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-TxB2 plus 11-dehydro-2,3-dinor-TxB2, 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 TxA2 production, in the absence of platelet COX-1 activity, between those with vs. without atherothrombotic MI were not observed when TxA2 generation was assessed on 11-dehydro-TxB2 production alone (polyclonal ELISA or LC-MS/MS), but differences were observed when TxA2 generation was assessed using 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2 (monoclonal ELISA). These findings highlight important differences between different commercially available assays for TxA2 generation and suggest that 11-dehydro-2,3-dinor-TxB2 may be critical to the biology of atherothrombosis.

Original languageEnglish (US)
Pages (from-to)2786-2792
Number of pages7
JournalCirculation Journal
Volume77
Issue number11
DOIs
StatePublished - Oct 31 2013

Keywords

  • Aspirin resistance
  • Atherothrombosis
  • Thromboxane

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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