title: Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin.
abstract: OBJECTIVE
  The purpose of this study was to compare the effects of low-to-high doses of aspirin on platelet aggregability determined by different methods and on the metabolism of thromboxane A2 and prostacyclin.
  
  
  METHODS
  We administered increasing doses (40, 320, and 1,280 mg/day) of aspirin to 19 poststroke patients and studied the differences in 1) the changes in platelet aggregability depending on the methods of evaluation and 2) the concentrations of prostaglandin metabolites in the blood and urine.
  
  
  RESULTS
  Aggregation of platelet-rich plasma induced by a strong stimulus (10 microM ADP) was significantly reduced after 40 mg/day aspirin (p less than 0.005), and this reduction was similar to that after higher aspirin doses. In contrast, aggregation of platelet-rich plasma induced by weaker stimuli (1 and 5 microM ADP) decreased less significantly after 40 mg/day aspirin compared with that after higher aspirin doses. The serum thromboxane B2 generated after ex vivo incubation was reduced significantly (by 85%) after 40 mg/day aspirin and decreased further after 320 mg/day (by 96%) and 1,280 mg/day (by greater than 99%) of aspirin. The urinary 11-dehydro-thromboxane B2 concentration decreased less significantly after 40 mg/day aspirin (by 42%) compared with that after 320 mg/day (by 78%) and 1,280 mg/day (by 91%) aspirin doses. The urinary concentration of 2,3-dinor-6-keto-prostaglandin F1 alpha did not decrease after 40 mg/day aspirin but decreased significantly after higher doses of aspirin.
  
  
  CONCLUSIONS
  These findings suggest that different doses of aspirin may be necessary to prevent thrombogenesis induced by different triggers of different strengths and that 40 mg/day aspirin is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.
authors.affiliation: Department of Neurology, Iwate Medical University, Morioka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tohgi
authors.forename: S
authors.initials: S
authors.lastname: Konno
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: B
authors.initials: B
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Kawano
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000652:urine; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D002561:Cerebrovascular Disorders / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D013928:Thromboxane A2 / Q000097:blood / Q000378:metabolism*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine
chemical_list: D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; C049235:11-dehydro-thromboxane B2; D011464:Epoprostenol; D001241:Aspirin