title: COX-2 Inhibition by Use of Rofecoxib or High Dose Aspirin Enhances ADP-Induced Platelet Aggregation in Fresh Blood.
abstract: OBJECTIVE
  Increased cardiovascular risk after use of selective or nonselective cyclooxygenase-2 (COX-2)-inhibitors might partly be caused by enhanced platelet aggregability. However, an effect of COX-2 inhibition on platelets has so far not been observed in humans.
  
  
  METHODS
  We tested in healthy volunteers the effect of COX-2-inhibition nearly in-vivo, i.e. immediately after and even during blood sampling.
  
  
  RESULTS
  Measurement within 2 minutes after venipuncture, but not 60 minutes later, showed that 50 mg of rofecoxib (n=12) or 500 (n=8) or 1000 (n=8) mg of aspirin increased ADP-induced platelet aggregation in a whole-blood aggregometer to, respectively, 152, 176 and 204 % of basal level (p<0.01). No significant differences in aggregability were observed after ingestion of 80 mg of aspirin (n=16), or placebo (n=8). Plasma 6-keto-PGF1α was decreased to 74 % after rofecoxib and to 76 and 70 % after 500 and 1000 mg of aspirin but did not change after low dose aspirin. Continuous photometrical measurement of aggregation in blood flowing from a cannulated vein revealed that high dose aspirin did not elicit aggregation by itself, but increased ADP-induced aggregation in proportion to the decrease in prostacyclin formation (r=0.68, p = 0.004). Since in these experiments thromboxane production was virtually absent, the enhanced aggregation after partial COX-2 inhibition was not caused by unopposed thromboxane formation.
  
  
  CONCLUSIONS
  We conclude that both selective and nonselective COX-2 inhibition enhances ADP-induced platelet aggregation in humans. This effect can only be detected during or immediately after venipuncture, possibly because of the short half-life of prostacyclin.
authors.affiliation: Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: Piet
authors.initials: P
authors.lastname: Borgdorff
authors.forename: M Louis
authors.initials: ML
authors.lastname: Handoko
authors.forename: Yeun Ying
authors.initials: YY
authors.lastname: Wong
authors.forename: Geert Jan
authors.initials: GJ
authors.lastname: Tangelder