Document Detail

COX-2 Inhibition by Use of Rofecoxib or High Dose Aspirin Enhances ADP-Induced Platelet Aggregation in Fresh Blood.
MedLine Citation:
PMID:  21331307     Owner:  NLM     Status:  PubMed-not-MEDLINE    
AIM: 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.
Piet Borgdorff; M Louis Handoko; Yeun Ying Wong; Geert Jan Tangelder
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Publication Detail:
Type:  Journal Article     Date:  2010-10-21
Journal Detail:
Title:  The open cardiovascular medicine journal     Volume:  4     ISSN:  1874-1924     ISO Abbreviation:  Open Cardiovasc Med J     Publication Date:  2010  
Date Detail:
Created Date:  2011-02-18     Completed Date:  2011-07-14     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101480504     Medline TA:  Open Cardiovasc Med J     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  198-205     Citation Subset:  -    
Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
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