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Updated: Apr 11, 2026
09:13
Turbidimetry on Human Washed Platelets: The Effect of the Pannexin1-inhibitor Brilliant Blue FCF on Collagen-induced Aggregation
Published on: April 6, 2017
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Circulating primers enhance platelet function and induce resistance to antiplatelet therapy
T A Blair1, S F Moore1, I Hers1
1School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
Journal of Thrombosis and Haemostasis : JTH
|June 4, 2015
Summary
Platelet primers can cause resistance to antiplatelet drugs like aspirin. Phosphoinositide 3-kinase (PI3K) plays a role in this resistance, offering potential therapeutic targets for thrombosis patients.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Hematology
Background:
- Aspirin and P2Y12 antagonists are key antiplatelet drugs for thrombosis.
- Patient resistance to these therapies elevates risks for acute coronary syndromes.
- Altered platelet primers and hyperactivity are linked to this resistance.
Purpose of the Study:
- Investigate the role of platelet primers in antiplatelet therapy resistance.
- Determine if phosphoinositide 3-kinase (PI3K) contributes to this resistance mechanism.
Main Methods:
- Assessed platelet aggregation, thromboxane A2 production, and ex vivo thrombus formation.
- Utilized potent P2Y12 inhibitor AR-C66096 and aspirin.
- Tested platelet primers (IGF-1, TPO) and epinephrine in the presence of antiplatelet drugs and PI3K inhibitors (wortmannin, LY294002).
Main Results:
- Platelet primers significantly counteracted the inhibitory effects of antiplatelet drugs.
- Insulin-like growth factor-1 (IGF-1) and thrombopoietin (TPO) mediated enhancements were blocked by PI3K inhibitors.
- Epinephrine-mediated enhancements were not affected by PI3K inhibitors.
Conclusions:
- Platelet primers are identified as a factor contributing to antiplatelet resistance.
- Both PI3K-dependent and PI3K-independent pathways are involved in primer-mediated resistance to antiplatelet therapy.
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