Janice Richardson asks, “I know that once you have taken aspirin, a platelet cannot produce thromboxane A2. Can this same platelet be activated in another way, say through the thrombin receptor on the platelet? Thanks for your help.”
Thank you for your question, Janice. Yes, aspirin acetylates platelet cyclooxygenase and slows thromboxane A2 production. Thromboxane A2 is a key platelet activator. When someone takes a single aspirin, there is about a 40-minute period following intestinal absorption in which acetylation occurs. After about an hour, all that remains in the circulation is salicylic acid, which persists for a few hours but has no further platelet effect. So the acetylation period is rather short and we go on producing functional platelets. This is the main reason we don’t bleed after taking an aspirin.
There is an alternative platelet activation pathway, the diacylglyceryl pathway, which produces inositol triphosphate and diacylglycerol, both platelet activators. It is not clear how much of a role this plays, but it may respond to different agonists than the cyclooxygenase pathway.
Finally, acetylated platelets are still able to adhere to the blood vessel lining through von Willebrand factor and collagen receptors.
By the way, in chronic inflammation or rapid platelet turnover, cyclooxygenase 2 (COX-2) is produced in megakaryocytes and is found in platelets. COX-2 acetylation does not slow platelet activation as effectively as COX-1 acetylation. This may be the mechanism behind so-called “aspirin resistance.” Geo.
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