title: Dose-dependent inhibition of platelet function by acetaminophen in healthy volunteers.
abstract: BACKGROUND
  Acetaminophen (paracetamol) is widely used for postoperative analgesia. Its mechanism of action is inhibition of prostaglandin synthesis in the central nervous system, and acetaminophen is traditionally not considered to influence platelet function. The authors studied the dose-dependent inhibition of platelet function by acetaminophen in healthy volunteers.
  
  
  METHODS
  Thirteen healthy male volunteers (aged 19-26 yr) were given placebo or 15, 22.5, or 30 mg/kg acetaminophen intravenously in a double-blind, crossover study. Ten and 90 min after infusion, platelet function was assessed by photometric aggregometry and by measuring release of thromboxane B2, analgesia by cold pressor test, and plasma acetaminophen concentrations by high-performance liquid chromatography.
  
  
  RESULTS
  When triggered with 500 microm arachidonic acid, median platelet aggregation (area under the curve) was 25.7, 22.8, 4.1, or 3.6 x 10 area units (P < 0.001) 10 min after placebo or 15, 22.5, or 30 mg/kg acetaminophen, respectively. An increasing concentration of arachidonic acid attenuated the antiaggregatory effect. After 90 min, platelet function was recovering. Release of thromboxane B2 was also dose-dependently inhibited by acetaminophen. Although plasma concentration of acetaminophen increased linearly with the dose, no analgesic effect was detected in the cold pressor test.
  
  
  CONCLUSIONS
  Acetaminophen, which is a weak inhibitor of platelet cyclooxygenase 1, has a dose-dependent antiaggregatory effect. This property may become clinically significant in patients with intrinsic or drug-induced impairment of hemostasis.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Edward
authors.initials: E
authors.lastname: Munsterhjelm
authors.forename: Nina M
authors.initials: NM
authors.lastname: Munsterhjelm
authors.forename: Tomi T
authors.initials: TT
authors.lastname: Niemi
authors.forename: Olavi
authors.initials: O
authors.lastname: Ylikorkala
authors.forename: Pertti J
authors.initials: PJ
authors.lastname: Neuvonen
authors.forename: Per H
authors.initials: PH
authors.lastname: Rosenberg
mesh_terms: D000082:Acetaminophen / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism
chemical_list: D018712:Analgesics, Non-Narcotic; D010975:Platelet Aggregation Inhibitors; D000082:Acetaminophen; D013929:Thromboxane B2