title: Effect of a single dose aspirin on platelets in humans with multiple risk factors for coronary artery disease.
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.
authors.affiliation: Center for Thrombosis Research, Sinai Hospital of Baltimore, Johns Hopkins University, 2401 West Belvedere Avenue, Schapiro Research Building R 202, Baltimore, MD 21215, USA.
authors.forename: Alex I
authors.initials: AI
authors.lastname: Malinin
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Callahan
authors.forename: Marcus E
authors.initials: ME
authors.lastname: McKenzie
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology*; D003324:Coronary Artery Disease / Q000097:blood* / Q000517:prevention & control; D005260:Female; D005434:Flow Cytometry / Q000295:instrumentation / Q000379:methods; D006801:Humans; D039564:Integrin alphaV / Q000097:blood / Q000187:drug effects; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000187:drug effects; D052118:Lysosomal-Associated Membrane Protein 1; D051907:Lysosomal Membrane Proteins; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects; D012307:Risk Factors; D060185:Tetraspanin 24; D060149:Tetraspanin 30; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; C554715:CD151 protein, human; C554586:CD63 protein, human; D039564:Integrin alphaV; D018950:Lipopolysaccharide Receptors; D052118:Lysosomal-Associated Membrane Protein 1; D051907:Lysosomal Membrane Proteins; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D060185:Tetraspanin 24; D060149:Tetraspanin 30; D001241:Aspirin