Whole blood aggregometry for evaluation of the antiplatelet effects of clopidogrel.
BACKGROUND
The marked interindividual variability in platelet inhibition even after administration of high loading doses of clopidogrel raised the question whether monitoring of antiplatelet effects in patients undergoing percutaneous coronary intervention (PCI) can improve clinical outcome. Established methods for monitoring antiplatelet drug activity such as optical aggregometry and determination of surface protein expression are not suitable for routine bedside testing.


METHODS
We therefore compared the applicability of whole blood impedance aggregometry (20 micromol/L ADP) and the whole blood bedside ULTEGRA assay with ADP-cartridges (20 micromol/L) with optical aggregometry in platelet-rich plasma and determination of surface protein expression (P-Selectin and activated GPIIb/IIIa) by flow cytometry. We analyzed samples obtained from 27 patients scheduled for elective PCI who received a loading dose of 600 mg of clopidogrel. Blood samples were withdrawn before clopidogrel, before PCI and 24h thereafter.


RESULTS
Platelet aggregation assessed by optical aggregometry (20 micromol/L ADP) declined from 65+/-9% (baseline) to 42+/-12% (PCI) and 45+/-13% (24h; p<0.01). Expression of surface proteins displayed a similar time course. Platelet aggregation determined by impedance aggregometry decreased from 4.6+/-4.0 Omega (baseline) to 0.1+/-0.3 Omega (PCI) and 0.5+/-1.1 Omega (24h) with no detectable residual platelet aggregation during PCI in 88% of patients. The ULTEGRA assay showed only slight changes after administration of clopidogrel. Correlation analysis between the various assays revealed significant correlations only between optical aggregometry and flow cytometry.


CONCLUSIONS
The results indicate that both of the whole blood assays cannot substitute for optical aggregometry or determination of surface proteins in the assessment of clopidogrel-induced platelet inhibition.
Hochholzer
Willibald
W
Herz-Zentrum Bad Krozingen, D-79189 Bad Krozingen, Germany. willibald.hochholzer@herzzentrum.de
Trenk
Dietmar
D
Frundi
Devine
D
Neumann
Franz-Josef
FJ
D015906:Angioplasty, Balloon, Coronary; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008991:Monitoring, Physiologic; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests / Q000295:instrumentation / Q000379:methods; D011237:Predictive Value of Tests; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014914:Whole Blood Coagulation Time / Q000295:instrumentation / Q000379:methods
D000077144:Clopidogrel; D013988:Ticlopidine