Inhibition of Prostacyclin and Platelet Thromboxane A₂after Low-Dose Aspirin

Abstract

To compare the inhibitory effects of aspirin on prostaglandin synthesized by vessel walls and platelets, we obtained vein segments from five subjects before they were given 150 or 300 mg of aspirin and at various intervals afterward. We then measured prostacyclin (PGI2) synthesis with a radioimmunoassay for its stable metabolite, 6-keto-prostaglandin F1 alpha. Platelet production of thromboxane A2 was measured with a radioimmunoassay for its stable metabolite, thromboxane B2. Two hours after aspirin had been given, 81 to 100 per cent inhibition of PGI2 synthesis was demonstrated; 86 per cent inhibition was still evident in one subject tested eight hours after administration. Simultaneously, platelet production of thromboxane B2 was completely inhibited for more than 24 hours. We conclude that there is little difference between the initial inhibitory response of platelet cyclooxygenase and that of vessel-wall cyclooxygenase to these doses of aspirin. Our results also indicate that in male subjects the prolonged template bleeding time after aspirin is not the consequence of selective inhibition of platelet production of thromboxane.

Availability of endothelial von Willebrand factor and platelet function in diabetic patients infused with a vasopressin analogue

“…This hypothesis was regarded as unlikely in a previous paper [25], which showed that the levels of 6-oxo-PGFt~ (a by-product of prostacyclin) did not increase following DDAVP, and is conclusively ruled out in the present study. In fact, aspirin administered to a normal subject in a dose capable of inhibiting the synthesis of prostacyclin over 12 h before study [26], did not modify the platelet retention pattern following DDAVP.…”

“…Further work is necessary to characterize this anti-adhesive mechanism(s). Prostacyclin, a potent anti-aggregating/anti-adhesive prostaglandin synthesized by the endothelial cells [26] could be released with vWF/VIII-RAG and inhibit platelet retention. This hypothesis was regarded as unlikely in a previous paper [25], which showed that the levels of 6-oxo-PGFt~ (a by-product of prostacyclin) did not increase following DDAVP, and is conclusively ruled out in the present study.…”

Clinicopathologic Conference

“…A recent report from Sheffield, England has shown reduction of prostacyclin levels in the veins of subjects given different doses of aspirin. 9 It had been previously believed that if 300 mg of aspirin was given daily, only TXA 2 and not prostacyclin would be inhibited. If large doses, 900 mg, were given, both would be inhibited.…”

“…The two most recently studied and described in detail are thromboxane, a plateletaggregating agent produced by thrombocytes, and prostacyclin or PGI-2, which is released by blood vessel walls and is a potent inhibitor of platelet aggregation. 8,9 The production or release of both of these factors is inhibited by aspirin, and it has been suggested that the administration of aspirin to men over the age of 20 and women over the age of 40, on a chronic, long-term basis, may lessen the severity of arterial thrombosis and arteriosclerosis. 10 This has been severely challenged in the literature.…”

“…Several studies have shown the effect of aspirin on prostacyclin and thromboxane. 8,9 In these studies, aspirin was administered to healthy persons and the release of prostacyclin was measured from a small venule. Doses as low as 80 mg of aspirin significantly lowered the release of prostacyclin from blood vessel walls.…”