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Published on: March 15, 2022
Effect of a single dose aspirin on platelets in humans with multiple risk factors for coronary artery disease
Alex I Malinin1, Dan Atar, Kevin P Callahan
1Center for Thrombosis Research, Sinai Hospital of Baltimore, Johns Hopkins University, 2401 West Belvedere Avenue, Schapiro Research Building R 202, Baltimore, MD 21215, USA.
Insights
A single 325 mg aspirin tablet significantly reduces platelet aggregation and aspirin response units in individuals with cardiac risk factors. This dose also prolongs closure time and affects key platelet surface receptors, indicating broad antiplatelet effects.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Hematology
Background:
- Aspirin is widely used for cardiovascular disease prevention.
- Understanding aspirin's precise effects on platelet function in at-risk individuals is crucial.
- Non-enteric coated aspirin's impact on platelet receptors and function needs detailed assessment.
Purpose of the Study:
- To evaluate the effect of a single 325 mg non-enteric coated aspirin tablet on human platelet function.
- To assess changes in platelet aggregation, closure time, and receptor expression in subjects with coronary artery disease risk factors.
- To determine the reliability of the Ultegra Analyzer for monitoring aspirin therapy.
Main Methods:
- Analyzed data from 63 individuals with multiple cardiac risk factors.
- Measured platelet function using aggregometry, PFA-100(R) closure time, and Ultegra aspirin response units (ARU).
- Assessed platelet receptor expression (CD31, CD41, CD42b, etc.) and platelet-leukocyte formation.
Main Results:
- A single aspirin dose significantly decreased platelet-rich plasma aggregation (p<0.0001) and ARU (p<0.0001).
- Closure time was significantly prolonged (p<0.0001) post-aspirin administration.
- Moderate inhibition of most surface platelet receptors was observed, with significant effects on PAC-1, CD31, CD41, CD42, CD62p, and CD151 (p<0.05).
Conclusions:
- A single 325 mg aspirin dose significantly impacts platelet function and receptor expression in individuals with cardiac risk factors.
- These effects are likely due to cyclooxygenase-1 blockade, inhibiting prostanoid synthesis.
- The Ultegra Analyzer shows promise for clinical monitoring of aspirin therapy effectiveness.
Abstract:
We sought to assess how one tablet of non-enteric coated aspirin (325 mg) affects human platelets in subjects with risk factors for coronary artery disease. Data from 63 individuals with multiple cardiac risk factors were analyzed. Platelets were assessed twice at baseline (pre-aspirin), and after 3-4 h (post-aspirin). We employed 5 microM epinephrine-induced conventional aggregometry, closure time with epinephrine/collagen cartridge by PFA-100(R) (Dade-Behring), and aspirin response units (ARU) stimulated by propyl gallat with Ultegra (Accumetrics, San Diego, CA, USA) for measuring platelet function. In addition, the expression of platelet receptors was determined by using the following monoclonal antibodies: anti-CD31, CD41, CD42b, CD51/CD61, CD62p, CD63, CD107a, and CD151. Platelet-leukocyte formation was detected utilizing dual antibodies for a pan-platelet marker CD151, and CD14, a monocyte/macrophage marker. PAC-1 was used to measure fibrinogen-platelet binding. One pill of aspirin significantly decreased platelet-rich plasma (PRP) aggregation (74.18+/-16.75% vs. 24.92+/-8.64%; p<0.0001) and resulted in reduction of the aspirin response units (ARU) (662.24+/-65.65 vs. 451.05+/-69.31; p<0.0001). There was also prolongation of the closure time (194.4+/-25.3 vs. 258.63+/-55.61 s; p<0.0001). High correlation (r(2)=0.73-0.86) between platelet analyzer readings and aggregation was observed. One tablet of aspirin moderately inhibited expression of most surface platelet receptors measured, and such inhibition reached significance (p<0.05) for PAC-1, CD31, CD41, CD42, CD62p, and CD151. We conclude that a single dose of aspirin affects major platelet receptors, presumably directly or indirectly through the inhibition of prostanoids via platelet cyclooxygenase-1 blockade. The Ultegra Analyzer with a novel cartridge seems to be reliable in reflecting aspirins' effects on platelets and could be used in the future in clinical practice for monitoring aspirin therapy.
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