{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:01:59Z","timestamp":1783699319164,"version":"3.55.0"},"reference-count":29,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-15-00005"],"award-info":[{"award-number":["22-15-00005"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets accelerate fibrin formation and thrombin generation, two final reactions of the coagulation cascade. We investigated the effects of antiplatelet drugs on platelet impact in these reactions and platelet ability to expose PS. Washed human platelets were incubated with acetylsalicylic acid (ASA), ticagrelor, ASA in combination with ticagrelor, ruciromab (glycoprotein IIb-IIIa antagonist), or prostaglandin E1 (PGE1). Platelets were not activated or activated by collagen and sedimented in multiwell plates, and plasma was added after supernatant removal. Fibrin formation (clotting) was monitored in a recalcification assay by light absorbance and thrombin generation in a fluorogenic test. PS exposure was assessed by annexin V staining using flow cytometry. Ticagrelor (alone and in combination with ASA), ruciromab, and PGE1, but not ASA, prolonged the lag phase and decreased the maximum rate of plasma clotting and decreased the peak and maximum rate of thrombin generation. Inhibition was observed when platelets were not treated with exogenous agonists (activation by endogenous thrombin) and pretreated with collagen. Ticagrelor (alone and in combination with ASA), ruciromab, and PGE1, but not ASA, decreased PS exposure on washed platelets activated by thrombin and by thrombin + collagen. PS exposure on activated platelets in whole blood was lower in patients with acute coronary syndrome receiving ticagrelor + ASA in comparison with donors free of medications. These results indicate that antiplatelet drugs are able to suppress platelet coagulation activity not only in vitro but also after administration to patients.<\/jats:p>","DOI":"10.3390\/biom13071124","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:49:30Z","timestamp":1689295770000},"page":"1124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of Antiplatelet Drugs on Platelet-Dependent Coagulation Reactions"],"prefix":"10.3390","volume":"13","author":[{"given":"Ivan A.","family":"Muravlev","sequence":"first","affiliation":[{"name":"Chazov National Medical Research Center of Cardiology, Russian Ministry of Health, Academician Chazov Str., 15a, Moscow 121552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoly B.","family":"Dobrovolsky","sequence":"additional","affiliation":[{"name":"Chazov National Medical Research Center of Cardiology, Russian Ministry of Health, Academician Chazov Str., 15a, Moscow 121552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga A.","family":"Antonova","sequence":"additional","affiliation":[{"name":"Chazov National Medical Research Center of Cardiology, Russian Ministry of Health, Academician Chazov Str., 15a, Moscow 121552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana G.","family":"Khaspekova","sequence":"additional","affiliation":[{"name":"Chazov National Medical Research Center of Cardiology, Russian Ministry of Health, Academician Chazov Str., 15a, Moscow 121552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina K.","family":"Alieva","sequence":"additional","affiliation":[{"name":"Chazov National Medical Research Center of Cardiology, Russian Ministry of Health, Academician Chazov Str., 15a, Moscow 121552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry V.","family":"Pevzner","sequence":"additional","affiliation":[{"name":"Chazov National Medical Research Center of Cardiology, Russian Ministry of Health, Academician Chazov Str., 15a, Moscow 121552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey V.","family":"Mazurov","sequence":"additional","affiliation":[{"name":"Chazov National Medical Research Center of Cardiology, Russian Ministry of Health, Academician Chazov Str., 15a, Moscow 121552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gresele, P., Kleimanat, N.S., Lopez, J.A., and Page, C.P. (2017). Platelets in Thrombotic and Non-Thrombotic Disorders, Springer.","DOI":"10.1007\/978-3-319-47462-5"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/rth2.12107","article-title":"Integrating platelet and coagulation activation in fibrin clot formation","volume":"2","author":"Swieringa","year":"2018","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1160\/TH07-05-0322","article-title":"Factor Xa-driven thrombin generation in plasma: Dependency on the aminophospholipid density of membranes and inhibition by phospholipid-binding proteins","volume":"98","author":"Wielders","year":"2007","journal-title":"Thromb. Haemost."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"139365","DOI":"10.1080\/09537104.2022.2139365","article-title":"Effects of platelets activated by different agonists on fibrin formation and thrombin generation","volume":"34","author":"Muravlev","year":"2023","journal-title":"Platelets"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1055\/a-1450-8300","article-title":"Added value of blood cells in thrombin generation testing","volume":"121","author":"Wan","year":"2021","journal-title":"Thromb. Haemost."},{"key":"ref_6","unstructured":"Michelson, A.D., Cattaneo, M., Frelinger, A.L., and Newman, P.J. (2019). Platelets, Elsevier Academic Press. [4th ed.]."},{"key":"ref_7","unstructured":"Michelson, A.D., Cattaneo, M., Frelinger, A.L., and Newman, P.J. (2019). Platelets, Elsevier Academic Press. [4th ed.]."},{"key":"ref_8","unstructured":"Michelson, A.D., Cattaneo, M., Frelinger, A.L., and Newman, P.J. (2019). Platelets, Elsevier Academic Press. [4th ed.]."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1080\/0953710021000057839","article-title":"Safety, inhibition of platelet aggregation and pharmacokinetics of F(ab\u2019)2 fragments of the anti-glycoprotein IIb-IIIa monoclonal antibody FRaMon in high-risk coronary angioplasty","volume":"13","author":"Mazurov","year":"2002","journal-title":"Platelets"},{"key":"ref_10","first-page":"586","article-title":"Antiplatelet effects of glycoproteins IIb-IIIa antagonist monafram","volume":"90","author":"Mazurov","year":"2004","journal-title":"Ross. Fiziol. Zhurnal Im. I.M. Sechenova"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Braune, S., K\u00fcpper, J.-H., and Jung, F. (2020). Effect of Prostanoids on Human Platelet Function: An Overview. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239020"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1055\/s-0037-1614178","article-title":"Effect of sodium arachidonate on thrombin generation through platelet activation\u2013inhibitory effect of aspirin","volume":"84","author":"Altman","year":"2000","journal-title":"Thromb. Haemost."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1111\/j.1538-7836.2006.02088.x","article-title":"Recombinant factor VIIa reverses the inhibitory effect of aspirin or aspirin plus clopidogrel on in vitro thrombin generation","volume":"4","author":"Altman","year":"2006","journal-title":"J. Thromb. Haemost."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/j.1742-4658.2007.06207.x","article-title":"Dual P2Y12 receptor signaling in thrombin-stimulated platelets-involvement of phosphoinositide 3-kinase \u03b2 but not \u03b3 isoform in Ca2+ mobilization and procoagulant activity","volume":"275","author":"Schoenwaelder","year":"2008","journal-title":"FEBS J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1172\/JCI118859","article-title":"Inhibition of platelet-mediated tissue factor-induced thrombin generation by the mouse\/human chimeric 7E3 antibody. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and \u201cclinical restenosis\u201d","volume":"98","author":"Reverter","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1007\/s00018-012-1033-2","article-title":"Key role of integrin \u03b1IIb\u03b23 signaling to Syk kinase in tissue factor-induced thrombin generation","volume":"69","author":"Feijge","year":"2012","journal-title":"Cell Mol. Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1161\/01.ATV.0000092127.16125.E6","article-title":"Differential Involvement of the P2Y1 and P2Y12 receptors in platelet procoagulant activity","volume":"23","author":"Ravanat","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1111\/j.1538-7836.2008.03052.x","article-title":"Formation of coated platelets is regulated by the dense granule secretion of adenosine 5\u2032diphosphate acting via the P2Y12 receptor","volume":"6","author":"Kotova","year":"2008","journal-title":"J. Thromb. Haemost."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0049-3848(98)00029-2","article-title":"Glycoprotein IIb\/IIIa receptor antagonists inhibit the development of platelet procoagulant activity","volume":"90","author":"Pedicord","year":"1998","journal-title":"Thromb. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1046\/j.1538-7836.2003.00349.x","article-title":"Different effects of various anti-GPIIb-IIIa agents on shear-induced platelet activation and expression of procoagulant activity","volume":"1","author":"Goto","year":"2003","journal-title":"J. Thromb. Haemost."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1055\/s-0037-1613552","article-title":"Platelet phosphatidylserine exposure and procoagulant activity in clotting whole blood\u2013different effects of collagen, TRAP and calcium ionophore A23187","volume":"89","author":"Lindahl","year":"2003","journal-title":"Thromb. Haemost."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1365-2141.2011.09021.x","article-title":"Identification of signal transduction pathways involved in the formation of platelet subpopulations upon activation","volume":"157","author":"Topalov","year":"2012","journal-title":"Br. J. Haematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/j.1538-7836.2009.03719.x","article-title":"RGD-ligand mimetic antagonists of integrin \u03b1IIb\u03b23 paradoxically enhance GPVI-induced human platelet activation","volume":"8","author":"Jones","year":"2010","journal-title":"J. Thromb. Haemost."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1111\/j.1538-7836.2007.02691.x","article-title":"Coated-platelet levels are influenced by smoking, aspirin, and selective serotonin reuptake inhibitors","volume":"5","author":"Prodan","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1055\/s-0038-1646445","article-title":"A monoclonal antibody, VM64, reacts with a 130 kDa glycoprotein common to platelets and endothelial cells: Heterogeneity in antibody binding to human aortic endothelial cells","volume":"66","author":"Mazurov","year":"1991","journal-title":"Thromb. Haemost."},{"key":"ref_26","first-page":"134","article-title":"Mean platelet volume: Interrelation with platelet aggregation activity and glycoprotein IIb-IIIa and Ib expression levels","volume":"8","author":"Khaspekova","year":"2014","journal-title":"Biochem. (Mosc.) Suppl. Ser. B Biomed. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1080\/09537104.2017.1356452","article-title":"Platelet aggregation impacts thrombin generation assessed by calibrated automated thrombography","volume":"29","author":"Didelot","year":"2018","journal-title":"Platelets"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1111\/jth.13256","article-title":"Assessment of platelet-derived thrombogenicity with the total thrombus-formation analysis system in coronary artery disease patients receiving antiplatelet therapy","volume":"14","author":"Arima","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1080\/09537104.2017.1294680","article-title":"Thrombin generation test for evaluation of antiplatelet treatment in patients with coronary artery disease after percutaneous coronary intervention","volume":"29","author":"Berezovskaya","year":"2018","journal-title":"Platelets"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/7\/1124\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:11:45Z","timestamp":1760127105000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/7\/1124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,14]]},"references-count":29,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["biom13071124"],"URL":"https:\/\/doi.org\/10.3390\/biom13071124","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,14]]}}}