Inhibition of human platelet function in vitro and ex vivo by acetaminophen.
The effects of acetaminophen (APAP) in vitro, or ex vivo following APAP ingestion, on human platelet aggregation, 14C-5HT secretion, and thromboxane B2 (TxB2) formation were assessed. APAP added in vitro to citrated platelet-rich plasma (PRP) inhibited aggregation, secretion, and TxB2 formation induced by collagen, epinephrine, arachidonate, and the ionophore A23187, but had no effect on the responses induced by the endoperoxide analog U44069. Arachidonate-induced responses were inhibited by lower concentrations of APAP than were the responses to the other agonists. In PRP obtained 1 hour after ingestion of 650 mg or 1000 mg APAP, arachidonate-induced TxB2 formation was inhibited by 40-99% in five subjects tested, whereas inhibition of collagen- or epinephrine-induced TxB2 formation was less consistent. Aggregation and secretion responses were not altered by APAP ingestion in 4 of the 5 subjects, but were inhibited in the remaining subject, who had the highest plasma APAP levels. In contrast to aspirin and indomethacin, APAP-induced inhibition of collagen-stimulated TxB2 formation could be partially overcome with increasing collagen concentrations. No such partial correction occurred with epinephrine, however. In washed platelet suspensions labeled with 3H-arachidonate, both APAP and aspirin inhibited the formation of labeled PGD2 and PGE2, as well as TxB2. These results suggest that APAP acts in human platelets as a reversible inhibitor of cyclo-oxygenase, as found previously in other tissues, and that recent APAP ingestion can, on occasion, produce inhibition of platelet functional responses measured in vitro.
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Department of Medicine, St. Luke's-Roosevelt Hospital Center, New York, N.Y.
Weiss
H J
HJ
D000082:Acetaminophen / Q000097:blood / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000097:blood; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000001:Calcimycin / Q000037:antagonists & inhibitors; D003094:Collagen / Q000037:antagonists & inhibitors; D004837:Epinephrine / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors; D012701:Serotonin / Q000097:blood / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood
D001095:Arachidonic Acids; D010975:Platelet Aggregation Inhibitors; D012701:Serotonin; D000082:Acetaminophen; D000001:Calcimycin; D013929:Thromboxane B2; D003094:Collagen; D001241:Aspirin; D007213:Indomethacin; D004837:Epinephrine