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Clopidogrel attenuates coated-platelet production in patients undergoing elective coronary catheterization
Nicholas B Norgard1, S Saya, C L Hann
1School of Pharmacy and Pharmaceutical Sciences, Department of Pharmacy Practice, University at Buffalo, Buffalo, NY 14260-1200, USA. nicknorgard@mac.com
Insights
Clopidogrel significantly reduced coated-platelet formation in patients undergoing coronary angiography. This study shows a potential new antithrombotic mechanism for clopidogrel beyond standard platelet aggregation inhibition.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Pharmacology
Background:
- Coated-platelets are highly thrombotic and linked to increased thrombotic risk.
- P2Y12 inhibition has shown potential in reducing coated-platelet formation in vitro.
- This study investigates the in vivo effects of clopidogrel on coated-platelets.
Purpose of the Study:
- To evaluate the impact of clopidogrel administration on coated-platelet formation in patients.
- To determine if clopidogrel reduces the levels of coated-platelets in a clinical setting.
Main Methods:
- 27 patients undergoing elective coronary angiography were enrolled.
- Blood samples were collected at baseline, 24 hours post-clopidogrel, and 6 hours post-angiography.
- Coated-platelet levels were measured using convulxin and thrombin with or without adenosine diphosphate (ADP).
Main Results:
- Clopidogrel administration resulted in a significant 7.2% absolute reduction in coated-platelet levels (17.8% relative reduction).
- Coated-platelet production stimulated by convulxin, thrombin, and ADP was significantly lowered by clopidogrel.
- The study provides the first evidence of in vivo P2Y12 antagonist effects on coated-platelet formation.
Conclusions:
- In vivo administration of clopidogrel partially attenuates coated-platelet formation.
- This effect may represent a novel antithrombotic mechanism of clopidogrel.
- Further research is needed to determine the clinical significance of this finding.
Introduction:
Coated-platelets are a subclass of highly thrombotic activated platelets with an enhanced ability to generate thrombin. Excessive numbers of coated-platelets are believed to increase thrombotic risk. A previous report demonstrated that P2Y12 inhibition in vitro attenuates coated-platelet formation. The aim of this study was to determine the effect clopidogrel has on coated-platelet formation.
Methods And Results:
We enrolled 27 patients undergoing elective coronary angiography. A total of 3 blood samples were taken from eligible patients: baseline, 24-hour postclopidogrel (preangiography), and 6-hour postangiography. Coated-platelet levels, expressed as percentage of total platelets, were determined with convulxin and thrombin with or without 1.5 or 6 microM adenosine diphosphate (ADP). Baseline levels of coated-platelets were 40.0% +/- 14.3% (mean +/- 1 SD). After clopidogrel exposure, the coated-platelet level was 32.8% +/- 13.6%, representing a significant 7.2% absolute reduction (AR) (17.8% relative reduction (RR); P < 0.0001). Clopidogrel significantly lowered the convulxin, thrombin plus ADP coated-platelet production (11.0% AR; 20.1% RR for 1.5 microM and 11.2% AR; 19.1% RR for 6 microM).
Conclusions:
This is the first report on the impact of in vivo administration of a P2Y12 antagonist on coated-platelet formation. The significance of a partial attenuation in coated-platelet potential has yet to be determined, but this could represent a new antithrombotic mechanism of clopidogrel beyond inhibition of ADP-induced aggregation.
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