Platelet thromboxane (11-dehydro-Thromboxane B2) and aspirin response in patients with diabetes and coronary artery disease

Figure 1 A schematic representation of the arachidonic/thromboxane metabolic pathway: Arachidonic acid generated from membrane phospholipids by phospholipase A2 and phospholipase C undergoes additional enzymatic transformation by cyclooxygenases (COX-1 and COX-2) into prostaglandin and thromboxane metabolites. In platelets, Arachidonic acid (AA) is metabolized by COX-1 into prostaglandins PGG₂, PGH₂ and by thromboxane synthase into the bioactive thromboxane A₂ (TXA₂), which is a potent activator of platelet aggregation with a short half-life. TXA₂ is quickly inactivated into a more stable thromboxane B₂ (TXB₂) and converted in the liver into an 11-dehydro-thromboxane B₂ (11dhTXB₂) metabolite excreted in the urine. Aspirin (ASA) irreversibly inhibits platelet COX-1 leading to decreased thromboxane-mediated platelet activation. TXA₂ and 11dhTXB₂ can be generated by COX-2 present in various inflammatory cells, pathway not affected by ASA.