Abstract 19439: Platelet COX-1 Independent TXA2 Generation in Acute Coronary Syndrome
Introduction: Platelet activation via thromboxane A2 (TXA2) is fundamental to thrombus formation in acute coronary syndrome (ACS) patients. Aspirin inhibits platelet TXA 2 production by inhibiting the cyclooxygenase (COX-1) enzyme in platelets. Emerging data suggest, however, that ACS patients continue to generate TXA2 despite aspirin therapy, but it is unclear whether this TXA2 is from a failure of aspirin to inhibit platelet COX-1 or from platelet COX-1 independent sources.
Hypothesis: Persistent TXA2 generation during ACS is derived from platelet COX-1 independent sources.
Methods: Platelet COX-1 independent TXA2 generation was evaluated in 25 patients on aspirin undergoing coronary angiography for stable and unstable angina. Platelet COX-1 activity was assessed by light transmission aggregation to 0.5mmol L−1 of arachidonic acid (<10% aggregation defines appropriate aspirin inhibition of platelet COX-1 activity). TXA2 was evaluated by ELISA measurement of urine 11-dehydro thromboxane B2 (UTXB2), a stable metabolite of TXA2.
Results: Platelet COX-1 activity was appropriately inhibited in all patients. UTXB2 levels in the ACS patients, however, was significantly greater than in those referred for non-ACS indications (1165 vs 766 pg/mg creatinine, p=0.029).
Conclusions: These data quantify platelet COX-1 independent TXA2 generation in patients with and without ACS who have arachidonic acid aggregometry proven adequate aspirin action. TXA2 generation is increased despite aspirin therapy in ACS and is derived from platelet COX-1 independent sources. Further investigation of the role of platelet COX-1 independent TXA generation with respect to platelet activation, coronary thrombosis and clinical outcomes during ACS is warranted. Figure: Difference in UTXB2 among participants undergoing coronary angiography with and without a primary indication of ACS and confirmed aspirin suppression of platelet COX−1.
- © 2010 by American Heart Association, Inc.