| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received on December 19, 2004
Accepted on March 14, 2005
Hemostasis and Thrombosis |
1 Institut für Klinische Biochemie und Pathobiochemie und Zentrallabor, and These authors contributed equally to this publication
2 Institut für Klinische Biochemie und Pathobiochemie und Zentrallabor
3 Rudolf-Virchow Zentrum für Experimentelle Biomedizin, Universität Würzburg, Würzburg, Germany
4 vasopharm BIOTECH GmbH, Würzburg, Germany
* To whom correspondence should be addressed. E-mail: Geiger{at}klin-biochem.uni-wuerzburg.de.
Background: Clopidogrel is a potent drug for prevention of adverse effects during and after coronary intervention. Increasing experience indicates that a significant proportion of patients do not respond adequately to clopidogrel. Because failure of antiplatelet therapy can have severe consequences, there is need for a reliable assay to quantify the effectiveness of clopidogrel treatment.
Methods: Of 24 healthy volunteers admitted to the study, 18 were treated for 1 week with clopidogrel (300-mg loading dose and 75-mg maintenance dose), and 6 with placebo. Platelet function was monitored by 2 assays, based on flow cytometry and enzyme immunoassay, that measure the phosphorylation status of vasodilator-stimulated phosphoprotein (VASP) and by aggregometry, flow cytometry of P-selectin, and the platelet function analyzer at baseline, on days 1-5, and on day 9 of treatment.
Results: Aggregometry and VASP phosphorylation revealed a loss of platelet response to ADP within 12 h after clopidogrel intake. The phosphorylation status of VASP correlated with the inhibition of platelet aggregation. In contrast, neither P-selectin expression nor PFA-100 closure time was a clear indicator of clopidogrel effects on platelets.
Conclusions: VASP phosphorylation assays are reliable for quantifying clopidogrel effects. Because the VASP assay directly measures the function of the clopidogrel target, the P2Y12 receptor, the assay is selective for clopidogrel effects rather than effects of other platelet inhibitors commonly in use.
The following articles in journals at HighWire Press have cited this article:
|
|
 |
|
  L. Wallentin P2Y12 inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use Eur. Heart J., August 2, 2009; 30(16): 1964 - 1977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. T. Ivandic, M. Sausemuth, H. Ibrahim, E. Giannitsis, M. Gawaz, and H. A. Katus Dual Antiplatelet Drug Resistance Is a Risk Factor for Cardiovascular Events after Percutaneous Coronary Intervention Clin. Chem., June 1, 2009; 55(6): 1171 - 1176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Price Bedside Evaluation of Thienopyridine Antiplatelet Therapy Circulation, May 19, 2009; 119(19): 2625 - 2632. [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Cairns and J. Eikelboom The Pursuit of Clinically Relevant Measures of Platelet Function After Antiplatelet Drug Therapy J. Am. Coll. Cardiol., December 9, 2008; 52(24): 1978 - 1980. [Full Text] [PDF]
|
|
|
|
|
|
M. Lordkipanidze, C. Pharand, T. A. Nguyen, E. Schampaert, D. A. Palisaitis, and J. G. Diodati Comparison of four tests to assess inhibition of platelet function by clopidogrel in stable coronary artery disease patients Eur. Heart J., December 1, 2008; 29(23): 2877 - 2885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Siller-Matula, I. Lang, G. Christ, and B. Jilma Calcium-Channel Blockers Reduce the Antiplatelet Effect of Clopidogrel J. Am. Coll. Cardiol., November 4, 2008; 52(19): 1557 - 1563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Douketis, P. B. Berger, A. S. Dunn, A. K. Jaffer, A. C. Spyropoulos, R. C. Becker, and J. Ansell The Perioperative Management of Antithrombotic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 299S - 339S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Muller-Schunk, J. Linn, N. Peters, M. Spannagl, M. Deisenberg, H. Bruckmann, and T.E. Mayer Monitoring of Clopidogrel-Related Platelet Inhibition: Correlation of Nonresponse with Clinical Outcome in Supra-Aortic Stenting AJNR Am. J. Neuroradiol., April 1, 2008; 29(4): 786 - 791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gilard, B. Arnaud, J.-C. Cornily, G. Le Gal, K. Lacut, G. Le Calvez, J. Mansourati, D. Mottier, J.-F. Abgrall, and J. Boschat Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin: The Randomized, Double-Blind OCLA (Omeprazole CLopidogrel Aspirin) Study J. Am. Coll. Cardiol., January 22, 2008; 51(3): 256 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-W. Lee, Y.-H. Cho, Y.-H. Kim, J.-S. Na, H. B. Shin, C.-S. Ki, T.-Y. Choi, and Y. K. Lee Aspirin Non-Responsiveness in Korean Subjects on Dual Anti-Platelet Treatment Determined by Two Different Platelet Function Assays Ann. Clin. Lab. Sci., January 1, 2008; 38(2): 126 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gachet and B. Aleil Testing antiplatelet therapy Eur. Heart J. Suppl., January 1, 2008; 10(suppl_A): A28 - A34. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Alfonso and D. J. Angiolillo Platelet Function Assessment to Predict Outcomes After Coronary Interventions: Hype or Hope? J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1751 - 1754. [Full Text] [PDF]
|
|
|
|
|
|
T. Geisler, H. Langer, M. Wydymus, K. Gohring, C. Zurn, B. Bigalke, K. Stellos, A. E. May, and M. Gawaz Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation Eur. Heart J., October 2, 2006; 27(20): 2420 - 2425. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
