Effects of platelet glycoprotein IIb-IIIa number and glycoprotein IIIa Leu33Pro polymorphism on platelet aggregation and sensitivity to glycoprotein IIb-IIIa antagonists. Platelets, 18(7):506-514, 2007. cited By 21![Effects of platelet glycoprotein IIb-IIIa number and glycoprotein IIIa Leu33Pro polymorphism on platelet aggregation and sensitivity to glycoprotein IIb-IIIa antagonists [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex We investigated the influence of glycoprotein (GP) IIIa Leu33Pro polymorphism, platelet GP IIb-IIIa number, and plasma fibrinogen concentration on platelet aggregation and antiaggregatory action of GP IIb-IIIa antagonists. Healthy volunteers with GP IIIa Pro33(-) (Leu33Leu33, n = 20) and Pro33(+) (Leu33Pro33, n = 13, and Pro33Pro33, n = 2) genotypes were included into the study. GP IIIa Leu33Pro substitution was associated with the increase of the level and rate of platelet microaggregate formation induced by GP IIb-IIIa activating antibody CRC54 (100, 200, 400 μg/ml) against the epitope within 1-100 residues of GP IIIa N-terminal part (p from 0.001 to 0.047). No significant differences were detected between parameters of platelet aggregation induced by ADP (1.25, 2.5, 5.0, 20 μM) in GP IIIa Pro33(+) and Pro33(-) donors. GP IIb-IIIa antagonist Monafram (F(ab')2 fragment of GP-IIb-IIIa blocking antibody CRC64) (1, 2, 3 μg/ml), but not eptifibatide (50, 100, 150 ng/ml) inhibited ADP-induced aggregation slightly less efficiently in GP IIIa Pro33(+) group (p < 0.05 at 1 and 2 μg/ml Monafram). GP IIb-IIIa number (evaluated as maximal binding of 125I-labelled antibody CRC64) varied from 40.5 to 80.8 × 103 per platelet with no significant influence of GP IIIa genotype. Consistent correlations were revealed between GP IIb-IIIa quantity and the level and rate of ADP-induced aggregation (r from 0.353 to 0.583, p from <0.001 to 0.037) as well as resistance (level of residual aggregation) to both GP IIb-IIIa antagonists (r from 0.345 to 0.602, p from <0.001 to 0.042). ADP-induced aggregation was considerably increased and efficiency of GP IIb-IIIa antagonists decreased in donors with high in comparison with low GP IIb-IIIa quantity (>60 and 40-50 × 103 per platelet respectively, p < 0.01 for most tests). No correlations were observed between all tested parameters and plasma fibrinogen concentration. Our results indicate that inter-individual variability of platelet GP IIb-IIIa number significantly affects platelet aggregation and antiaggregatory effects of GP IIb-IIIa antagonists. Contribution of this factor is higher than that of GP IIIa Leu33Pro polymorphism and variations of fibrinogen concentration. © 2007 Informa UK Ltd.
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{"_id":"94jqJLsM4yDCtKg7Q","bibbaseid":"anonymous-effectsofplateletglycoproteiniibiiianumberandglycoproteiniiialeu33propolymorphismonplateletaggregationandsensitivitytoglycoproteiniibiiiaantagonists-2007","bibdata":{"bibtype":"article","type":"article","author":[{"propositions":[],"lastnames":["Sirotkina"],"firstnames":["O.V."],"suffixes":[]},{"propositions":[],"lastnames":["Khaspekova"],"firstnames":["S.G."],"suffixes":[]},{"propositions":[],"lastnames":["Zabotina"],"firstnames":["A.M."],"suffixes":[]},{"propositions":[],"lastnames":["Shimanova"],"firstnames":["Y.V."],"suffixes":[]},{"propositions":[],"lastnames":["Mazurov"],"firstnames":["A.V."],"suffixes":[]}],"title":"Effects of platelet glycoprotein IIb-IIIa number and glycoprotein IIIa Leu33Pro polymorphism on platelet aggregation and sensitivity to glycoprotein IIb-IIIa antagonists","journal":"Platelets","year":"2007","volume":"18","number":"7","pages":"506-514","doi":"10.1080/09537100701326739","note":"cited By 21","url":"https://www.scopus.com/inward/record.uri?eid=2-s2.0-35648984592&doi=10.1080%2f09537100701326739&partnerID=40&md5=b5a28dc63e2ffabc049144b520c53c25","affiliation":"Petersburg Nuclear Physics Institute, Russian Academy of Sciences, Saint-Petersburg, Russian Federation; Russian Cardiology Research and Production Complex, Russian Ministry of Health, Moscow, Russian Federation; Russian Cardiology Research and Production Complex, 3rd Cherepkovskaya 15a, 121552 Moscow, Russian Federation","abstract":"We investigated the influence of glycoprotein (GP) IIIa Leu33Pro polymorphism, platelet GP IIb-IIIa number, and plasma fibrinogen concentration on platelet aggregation and antiaggregatory action of GP IIb-IIIa antagonists. Healthy volunteers with GP IIIa Pro33(-) (Leu33Leu33, n = 20) and Pro33(+) (Leu33Pro33, n = 13, and Pro33Pro33, n = 2) genotypes were included into the study. GP IIIa Leu33Pro substitution was associated with the increase of the level and rate of platelet microaggregate formation induced by GP IIb-IIIa activating antibody CRC54 (100, 200, 400 μg/ml) against the epitope within 1-100 residues of GP IIIa N-terminal part (p from 0.001 to 0.047). No significant differences were detected between parameters of platelet aggregation induced by ADP (1.25, 2.5, 5.0, 20 μM) in GP IIIa Pro33(+) and Pro33(-) donors. GP IIb-IIIa antagonist Monafram (F(ab')2 fragment of GP-IIb-IIIa blocking antibody CRC64) (1, 2, 3 μg/ml), but not eptifibatide (50, 100, 150 ng/ml) inhibited ADP-induced aggregation slightly less efficiently in GP IIIa Pro33(+) group (p < 0.05 at 1 and 2 μg/ml Monafram). GP IIb-IIIa number (evaluated as maximal binding of 125I-labelled antibody CRC64) varied from 40.5 to 80.8 × 103 per platelet with no significant influence of GP IIIa genotype. Consistent correlations were revealed between GP IIb-IIIa quantity and the level and rate of ADP-induced aggregation (r from 0.353 to 0.583, p from <0.001 to 0.037) as well as resistance (level of residual aggregation) to both GP IIb-IIIa antagonists (r from 0.345 to 0.602, p from <0.001 to 0.042). ADP-induced aggregation was considerably increased and efficiency of GP IIb-IIIa antagonists decreased in donors with high in comparison with low GP IIb-IIIa quantity (>60 and 40-50 × 103 per platelet respectively, p < 0.01 for most tests). No correlations were observed between all tested parameters and plasma fibrinogen concentration. Our results indicate that inter-individual variability of platelet GP IIb-IIIa number significantly affects platelet aggregation and antiaggregatory effects of GP IIb-IIIa antagonists. Contribution of this factor is higher than that of GP IIIa Leu33Pro polymorphism and variations of fibrinogen concentration. © 2007 Informa UK Ltd.","author_keywords":"Fibrinogen; Genetic polymorphism; Glycoprotein IIb-IIIa; GP IIb-IIIa antagonists; Platelet aggregation","funding_details":"Российский Фонд Фундаментальных Исследований (РФФИ)06-04-48186, 05-04-49116","key":"Sirotkina2007506","id":"Sirotkina2007506","bibbaseid":"anonymous-effectsofplateletglycoproteiniibiiianumberandglycoproteiniiialeu33propolymorphismonplateletaggregationandsensitivitytoglycoproteiniibiiiaantagonists-2007","role":"author","urls":{"Paper":"https://www.scopus.com/inward/record.uri?eid=2-s2.0-35648984592&doi=10.1080%2f09537100701326739&partnerID=40&md5=b5a28dc63e2ffabc049144b520c53c25"},"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bio.pnpi.nrcki.ru/wp-content/uploads/2019/12/lmgch_2019_10.txt","dataSources":["87fXC3NAxFNMB5YTH"],"keywords":[],"search_terms":["effects","platelet","glycoprotein","iib","iiia","number","glycoprotein","iiia","leu33pro","polymorphism","platelet","aggregation","sensitivity","glycoprotein","iib","iiia","antagonists"],"title":"Effects of platelet glycoprotein IIb-IIIa number and glycoprotein IIIa Leu33Pro polymorphism on platelet aggregation and sensitivity to glycoprotein IIb-IIIa antagonists","year":2007}