Congenital deficiency of thromboxane and prostacyclin.
Animal work suggests that with certain doses of aspirin the antithrombotic effect exerted via the inhibition of the proaggregatory platelet thromboxane A2 (TXA2) may be neutralised by the concomitant vascular reduction of the antiaggregatory prostacyclin (PGI2). Such a situation might result not only in therapeutic ineffectiveness but also in a thrombotic tendency. A patient with a bleeding disorder characterised by a mildly prolonged bleeding time and defective platelet-release reaction due to a congenital deficiency of cyclo-oxygenase provided an opportunity for studying this problem. Her platelets did not aggregate with arachidonic acid, but they did so with a synthetic endoperoxide analogue. Thrombin added to her platelet-rich plasma and whole blood did not generate thromboxane B2 (TXB2). Washed platelets, when incubated with 14C-arachidonic acid, did not produce the cyclo-oxygenase metabolites. A biopsy specimen of her vein did not generate PGI2, as measured both by platelet-aggregation inhibition and radioimmunoassay of 6-keto-PGF1 alpha. Clinically, the patient had a mild bleeding tendency but no thrombotic problems. The findings suggest that in man aspirin therapy, even at doses which inhibit PGI2 formation, would only impair haemostasis mildly without producing a thrombotic tendency.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001780:Blood Coagulation Tests / Q000379:methods; D001791:Blood Platelet Disorders / Q000151:congenital*; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer / Q000379:methods; D011464:Epoprostenol / Q000172:deficiency*; D006470:Hemorrhage / Q000209:etiology*; D006801:Humans; D008297:Male; D010105:Oxygenases / Q000172:deficiency*; D010949:Plasma; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000172:deficiency*; D013928:Thromboxane A2 / Q000172:deficiency*; D013931:Thromboxanes / Q000172:deficiency*
D001095:Arachidonic Acids; D011453:Prostaglandins; D013931:Thromboxanes; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D010105:Oxygenases; D001241:Aspirin