title: Reverse effect of aspirin: is the prothrombotic effect after aspirin discontinuation mediated by cyclooxygenase 2 inhibition?
abstract: BACKGROUND
  While aspirin is the drug most often used to prevent cardiovascular complications, its discontinuation induces an increased risk of acute coronary syndrome and ischemic stroke in some patients.
  
  
  OBJECTIVE
  We hypothesized that infinitesimal concentrations of aspirin could persist in plasma after its discontinuation, thereby inducing a prothrombotic effect that could be due to a modification in the mechanism of action of aspirin via the cyclooxygenase 1 (COX-1) and COX-2 pathways.
  
  
  RESULTS
  We studied the effects of ultra-low-dose aspirin (ULDA) as well as those of sc-560 and ns-398, specific COX-1 and COX-2 inhibitors, on induced hemorrhagic time and in a model of laser-induced thrombosis in rats. In the laser-induced thrombosis model, ULDA treatment increased the number of emboli and the duration of embolization, thereby confirming its prothrombotic effect described in previous publications. This effect was also observed in rats pretreated with sc-560 but not in those pretreated with ns-398.
  
  
  CONCLUSIONS
  We demonstrated that ULDA induced a prothrombotic effect in the rats studied. This strongly suggests that a very small amount of aspirin could remain in the patient's blood after aspirin therapy, leading to cardiovascular complications. This effect may be mediated by the COX-2 pathway.
authors.affiliation: Laboratoire d'Hématologie, UFR des Sciences Pharmaceutiques, Université Victor Segalen Bordeaux 2, Bordeaux, France. Christian.Doutremepuich@heph.u-bordeaux2.fr
authors.forename: Christian
authors.initials: C
authors.lastname: Doutremepuich
authors.forename: Omar
authors.initials: O
authors.lastname: Aguejouf
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Eizayaga
authors.forename: Vanessa
authors.initials: V
authors.lastname: Desplat
mesh_terms: D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D001760:Bleeding Time; D051545:Cyclooxygenase 1 / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007834:Lasers / Q000009:adverse effects; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D008657:Metabolic Clearance Rate; D009578:Nitrobenzenes / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000201:enzymology* / Q000209:etiology; D013449:Sulfonamides / Q000494:pharmacology; D019851:Thrombophilia / Q000139:chemically induced / Q000201:enzymology*; D013927:Thrombosis / Q000201:enzymology / Q000209:etiology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D001241:Aspirin