title: Aspirin prolongs bleeding time in uremia by a mechanism distinct from platelet cyclooxygenase inhibition.
abstract: We reported that aspirin (ASA) abnormally prolongs bleeding time (BT) in uremia. The present study was designed to investigate whether the abnormally prolonged post-ASA BT in uremia is due to different ASA pharmacokinetics and bioavailability that might be a consequence of uremic condition, platelet cyclooxygenase is peculiarly sensitive to ASA in uremia, and ASA affects primary hemostasis in uremia by a mechanism independent of cyclooxygenase inhibition. Our results showed that in patients with uremia, but not in normal subjects, ASA markedly prolongs the BT. This effect is transient and depends on the presence of ASA in the blood. The observed differences in ASA kinetic parameters are not an explanation of the exaggerated effect of ASA on primary hemostasis in uremia. The sensitivity of platelet cyclooxygenase to ASA inhibition is comparable in uremics and in normal subjects. The temporal dissociation between ASA-induced prolongation of BT and the effect on platelet thromboxane A2 generation suggests that ASA inhibits platelet function in uremia by a mechanism distinct from cyclooxygenase blocking. This possibility is strengthened by the observation that ibuprofen at a dose that fully inhibits platelet cyclooxygenase activity does not significantly prolong BT.
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000378:metabolism / Q000494:pharmacology*; D001760:Bleeding Time; D001792:Blood Platelets / Q000201:enzymology*; D016861:Cyclooxygenase Inhibitors; D005260:Female; D006474:Hemorrhagic Disorders / Q000209:etiology; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010979:Platelet Function Tests; D013928:Thromboxane A2 / Q000096:biosynthesis; D014511:Uremia / Q000097:blood* / Q000150:complications
chemical_list: D016861:Cyclooxygenase Inhibitors; D013928:Thromboxane A2; D001241:Aspirin; D007052:Ibuprofen