Insights into the interpretation of light transmission aggregometry for evaluation of platelet aggregation inhibition by clopidogrel.
BACKGROUND
When studying the efficacy of clopidogrel to inhibit platelet aggregation by light transmission aggregometry, technical decisions must be taken prior to assessment or during analysis, including, but not limited to, concentration of agonist to use and timing of the evaluation of the response on the aggregation curve obtained (peak ADP-stimulated platelet aggregation vs. late aggregation). We investigated how some of these technical modalities affected the results of platelet aggregation obtained after clopidogrel administration.


METHODS
One hundred and twenty stable coronary artery disease patients requiring a diagnostic angiography were recruited prior to pre-treatment with clopidogrel. Blood samples were tested before clopidogrel initiation and immediately preceding coronary angiography using light transmission aggregometry with either 5 or 20 microM of ADP. Aggregation was measured at maximal amplitude (peak), and 5 minutes after agonist addition (late).


RESULTS
While measurements of platelet aggregation as either peak or late aggregation were strongly correlated, peak platelet aggregation was significantly higher than late aggregation, by 10.8% and by 10.3% with ADP 5 and 20 microM, respectively. Moreover, the use of ADP 20 microM resulted in less spontaneous disaggregation than 5 microM in the absence of clopidogrel (11.8% and 4.8% with ADP 5 microM and 20 microM, respectively).


CONCLUSIONS
When assessing platelet aggregation following clopidogrel, measurement of late aggregation after addition of ADP 20 microM should be preferred. Large clinical trials should be conducted to assess which parameter between residual aggregation or inhibition of platelet aggregation by clopidogrel best predicts clinical efficacy of the drug.
Faculty of Pharmacy, Université de Montréal, Montréal, Canada.
Marie
M
Lordkipanidzé
Chantal
C
Pharand
Donald A
DA
Palisaitis
Erick
E
Schampaert
Jean G
JG
Diodati
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010979:Platelet Function Tests / Q000379:methods*; D011446:Prospective Studies; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine