{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:01:02Z","timestamp":1791576062160,"version":"4.3.4"},"reference-count":144,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["VIDI 723.013.009"],"award-info":[{"award-number":["VIDI 723.013.009"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Van de Laar Foundation","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The integrin \u03b1IIb\u03b23 is the most abundant integrin on platelets. Upon platelet activation, the integrin changes its conformation (inside-out signalling) and outside-in signalling takes place leading to platelet spreading, platelet aggregation and thrombus formation. Bloodsucking parasites such as mosquitoes, leeches and ticks express anticoagulant and antiplatelet proteins, which represent major sources of lead compounds for the development of useful therapeutic agents for the treatment of haemostatic disorders or cardiovascular diseases. In addition to hematophagous parasites, snakes also possess anticoagulant and antiplatelet proteins in their salivary glands. Two snake venom proteins have been developed into two antiplatelet drugs that are currently used in the clinic. The group of proteins discussed in this review are disintegrins, low molecular weight integrin-binding cysteine-rich proteins, found in snakes, ticks, leeches, worms and horseflies. Finally, we highlight various oral antagonists, which have been tested in clinical trials but were discontinued due to an increase in mortality. No new \u03b1IIb\u03b23 inhibitors are developed since the approval of current platelet antagonists, and structure-function analysis of exogenous disintegrins could help find platelet antagonists with fewer adverse side effects.<\/jats:p>","DOI":"10.3390\/ijms22073366","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T14:51:12Z","timestamp":1616683872000},"page":"3366","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Exogenous Integrin \u03b1IIb\u03b23 Inhibitors Revisited: Past, Present and Future Applications"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3221-1980","authenticated-orcid":false,"given":"Danique L.","family":"van den Kerkhof","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola E.J.","family":"van der Meijden","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman M.","family":"Hackeng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4586-3646","authenticated-orcid":false,"given":"Ingrid","family":"Dijkgraaf","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13045-019-0709-6","article-title":"Platelet integrin alphaIIbbeta3: Signal transduction, regulation, and its therapeutic targeting","volume":"12","author":"Huang","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s12551-013-0124-0","article-title":"Structural and mechanical functions of integrins","volume":"6","author":"Anderson","year":"2014","journal-title":"Biophys. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20","DOI":"10.4161\/cam.18702","article-title":"The regulation of integrin function by divalent cations","volume":"6","author":"Zhang","year":"2012","journal-title":"Cell Adhes. Migr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"25570","DOI":"10.1074\/jbc.270.43.25570","article-title":"Monoclonal antibody 9EG7 defines a novel beta 1 integrin epitope induced by soluble ligand and manganese, but inhibited by calcium","volume":"270","author":"Bazzoni","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/bies.20636","article-title":"The collagen family members as cell adhesion proteins","volume":"29","author":"Heino","year":"2007","journal-title":"Bioessays"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/j.1600-065X.2007.00536.x","article-title":"Integrin modulation and signaling in leukocyte adhesion and migration","volume":"218","author":"Rose","year":"2007","journal-title":"Immunol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/gb-2007-8-5-215","article-title":"The integrins","volume":"8","author":"Takada","year":"2007","journal-title":"Genome Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1172\/JCI26989","article-title":"Structure and function of the platelet integrin alphaIIbbeta3","volume":"115","author":"Bennett","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1182\/blood-2008-06-077891","article-title":"The GPIIb\/IIIa (integrin alphaIIbbeta3) odyssey: A technology-driven saga of a receptor with twists, turns, and even a bend","volume":"112","author":"Coller","year":"2008","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1242\/dev.01160","article-title":"alphavbeta3 integrin-dependent endothelial cell dynamics in vivo","volume":"131","author":"Rupp","year":"2004","journal-title":"Development"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e259","DOI":"10.3324\/haematol.2017.180927","article-title":"A novel variant Glanzmann thrombasthenia due to co-inheritance of a loss- and a gain-of-function mutation of ITGB3: Evidence of a dominant effect of gain-of-function mutations","volume":"103","author":"Bury","year":"2018","journal-title":"Haematologica"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1750-1172-1-10","article-title":"Glanzmann thrombasthenia","volume":"1","author":"Nurden","year":"2006","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.bpj.2013.07.055","article-title":"On the activation of integrin alphaIIbbeta3: Outside-in and inside-out pathways","volume":"105","author":"Mehrbod","year":"2013","journal-title":"Biophys. J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bury, L., Malara, A., Gresele, P., and Balduini, A. (2012). Outside-in signalling generated by a constitutively activated integrin alphaIIbbeta3 impairs proplatelet formation in human megakaryocytes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034449"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1111\/j.1538-7836.2007.02537.x","article-title":"Platelet integrin alpha(IIb)beta: Activation mechanisms","volume":"5","author":"Ma","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1089\/ars.2006.8.312","article-title":"Extracellular disulfide exchange and the regulation of cellular function","volume":"8","author":"Jordan","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Levin, L., Zelzion, E., Nachliel, E., Gutman, M., Tsfadia, Y., and Einav, Y. (2013). A single disulfide bond disruption in the beta3 integrin subunit promotes thiol\/disulfide exchange, a molecular dynamics study. PLoS ONE, 8.","DOI":"10.1371\/annotation\/b4e96e4b-3106-4040-a63c-a3f018f0e5c0"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"926968","DOI":"10.1155\/2012\/926968","article-title":"PGI2 as a regulator of inflammatory diseases","volume":"2012","author":"Dorris","year":"2012","journal-title":"Mediators Inflamm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5193","DOI":"10.1073\/pnas.87.13.5193","article-title":"An L-arginine\/nitric oxide pathway present in human platelets regulates aggregation","volume":"87","author":"Radomski","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1152\/physrev.00016.2011","article-title":"New fundamentals in hemostasis","volume":"93","author":"Versteeg","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1111\/j.1538-7836.2012.04797.x","article-title":"Contribution of platelet vs. endothelial VWF to platelet adhesion and hemostasis","volume":"10","author":"Kanaji","year":"2012","journal-title":"J. Thromb Haemost."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"236","DOI":"10.12688\/f1000research.13283.1","article-title":"The life cycle of platelet granules","volume":"7","author":"Sharda","year":"2018","journal-title":"F1000Res"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6217","DOI":"10.1038\/s41598-019-42701-0","article-title":"Quantitative dynamics of reversible platelet aggregation: Mathematical modelling and experiments","volume":"9","author":"Filkova","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1074\/jbc.274.8.4633","article-title":"A new model of dual interacting ligand binding sites on integrin alphaIIbbeta3","volume":"274","author":"Hu","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1182\/blood-2017-03-773614","article-title":"Integrin alphaIIbbeta3 outside-in signaling","volume":"130","author":"Durrant","year":"2017","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1182\/blood-2011-04-292128","article-title":"Reconstruction of integrin activation","volume":"119","author":"Ye","year":"2012","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1111\/jth.13302","article-title":"Platelet signaling: A complex interplay between inhibitory and activatory networks","volume":"14","author":"Bye","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00109-015-1346-3","article-title":"RAP1-GTPase signaling and platelet function","volume":"94","author":"Stefanini","year":"2016","journal-title":"J. Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11485","DOI":"10.1074\/jbc.M809233200","article-title":"Kindlin-1 and -2 directly bind the C-terminal region of beta integrin cytoplasmic tails and exert integrin-specific activation effects","volume":"284","author":"Harburger","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1126\/science.1174779","article-title":"G protein subunit Galpha13 binds to integrin alphaIIbbeta3 and mediates integrin \u201coutside-in\u201d signaling","volume":"327","author":"Gong","year":"2010","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1055\/s-2004-833478","article-title":"Protein-protein interactions in platelet alphaIIbbeta3 signaling","volume":"30","author":"Buensuceso","year":"2004","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1182\/blood-2009-04-217224","article-title":"Deletion of the p110beta isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo","volume":"115","author":"Martin","year":"2010","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1182\/blood-2009-03-208074","article-title":"Genetic evidence for a predominant role of PI3Kbeta catalytic activity in ITAM- and integrin-mediated signaling in platelets","volume":"114","author":"Canobbio","year":"2009","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.bbamem.2013.07.017","article-title":"Mechanisms of talin-dependent integrin signaling and crosstalk","volume":"1838","author":"Das","year":"2014","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1038\/nm1102-1227","article-title":"Platelets in atherothrombosis","volume":"8","author":"Ruggeri","year":"2002","journal-title":"Nat. Med."},{"key":"ref_36","first-page":"785","article-title":"Thrombosis and platelets: An update","volume":"38","author":"Koupenova","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_37","first-page":"120","article-title":"Risk factors for venous and arterial thrombosis","volume":"9","author":"Previtali","year":"2011","journal-title":"Blood Transfus."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1161\/CIRCULATIONAHA.118.033580","article-title":"Combination Antiplatelet and Oral Anticoagulant Therapy in Patients With Coronary and Peripheral Artery Disease","volume":"139","author":"Gurbel","year":"2019","journal-title":"Circulation"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1055\/s-2002-35293","article-title":"Pharmacology of recombinant hirudin","volume":"28","author":"Nowak","year":"2002","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1182\/blood.V92.9.3268","article-title":"Accutin, a new disintegrin, inhibits angiogenesis in vitro and in vivo by acting as integrin alphavbeta3 antagonist and inducing apoptosis","volume":"92","author":"Yeh","year":"1998","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0304-4165(98)00104-4","article-title":"A new short chain RGD-containing disintegrin, accutin, inhibits the common pathway of human platelet aggregation","volume":"1425","author":"Yeh","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"14248","DOI":"10.1021\/bi025876s","article-title":"A new gene structure of the disintegrin family: A subunit of dimeric disintegrin has a short coding region","volume":"41","author":"Okuda","year":"2002","journal-title":"Biochemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5225","DOI":"10.1021\/bi00235a016","article-title":"Identification of the disulfide bond pattern in albolabrin, an RGD-containing peptide from the venom of Trimeresurus albolabris: Significance for the expression of platelet aggregation inhibitory activity","volume":"30","author":"Calvete","year":"1991","journal-title":"Biochemistry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.toxicon.2007.08.002","article-title":"Molecular cloning of albolatin, a novel snake venom metalloprotease from green pit viper (Trimeresurus albolabris), and expression of its disintegrin domain","volume":"50","author":"Singhamatr","year":"2007","journal-title":"Toxicon"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8050","DOI":"10.1073\/pnas.86.20.8050","article-title":"Agkistrodon piscivorus piscivorus platelet aggregation inhibitor: A potent inhibitor of platelet activation","volume":"86","author":"Chao","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/0304-4165(91)90053-J","article-title":"Mechanism of action of the antiplatelet peptide, arietin, from Bitis arietans venom","volume":"1074","author":"Huang","year":"1991","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1006\/abbi.1998.0698","article-title":"Isolation, sequence analysis, and biological activity of atrolysin E\/D, the non-RGD disintegrin domain from Crotalus atrox venom","volume":"354","author":"Shimokawa","year":"1998","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.biochi.2014.10.010","article-title":"Isolation and characterization of four medium-size disintegrins from the venoms of Central American viperid snakes of the genera Atropoides, Bothrops, Cerrophidion and Crotalus","volume":"107","author":"Angulo","year":"2014","journal-title":"Biochimie"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.gene.2006.09.020","article-title":"Molecular evolution of PIII-SVMP and RGD disintegrin genes from the genus Crotalus","volume":"389","author":"Soto","year":"2007","journal-title":"Gene"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9359","DOI":"10.1016\/S0021-9258(18)92826-7","article-title":"Barbourin. A GPIIb-IIIa-specific integrin antagonist from the venom of Sistrurus m. barbouri","volume":"266","author":"Scarborough","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/S0021-9258(18)54041-2","article-title":"Characterization of the integrin specificities of disintegrins isolated from American pit viper venoms","volume":"268","author":"Scarborough","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0167-4889(90)90096-V","article-title":"Batroxostatin, an Arg-Gly-Asp-containing peptide from Bothrops atrox, is a potent inhibitor of platelet aggregation and cell interaction with fibronectin","volume":"1054","author":"Rucinski","year":"1990","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"21550","DOI":"10.1016\/S0021-9258(20)88220-9","article-title":"Characterization and platelet inhibitory activity of bitistatin, a potent arginine-glycine-aspartic acid-containing peptide from the venom of the viper Bitis arietans","volume":"264","author":"Shebuski","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_54","first-page":"253","article-title":"Isolation of bothrasperin, a disintegrin with potent platelet aggregation inhibitory activity, from the venom of the snake Bothrops asper","volume":"51","author":"Pinto","year":"2003","journal-title":"Rev. Biol. Trop."},{"key":"ref_55","first-page":"271","article-title":"Colombistatin: A disintegrin isolated from the venom of the South American snake (Bothrops colombiensis) that effectively inhibits platelet aggregation and SK-Mel-28 cell adhesion","volume":"83","author":"Palomar","year":"2008","journal-title":"Arch. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0049-3848(94)90052-3","article-title":"Purification and characterization of platelet aggregation inhibitors from snake venoms","volume":"73","author":"Trikha","year":"1994","journal-title":"Thromb. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1006\/abbi.1999.1682","article-title":"Molecular Cloning and Functional Expression of Contortrostatin, a Homodimeric Disintegrin from Southern Copperhead Snake Venom","volume":"375","author":"Zhou","year":"2000","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/0041-0101(95)00074-V","article-title":"Crotavirin, a potent platelet aggregation inhibitor purified from the venom of the snake Crotalus viridis","volume":"33","author":"Liu","year":"1995","journal-title":"Toxicon"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.thromres.2008.08.001","article-title":"Anti-platelet effect of cumanastatin 1, a disintegrin isolated from venom of South American Crotalus rattlesnake","volume":"123","author":"Lucena","year":"2009","journal-title":"Thromb. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1042\/bst021073s","article-title":"Dendroaspin: A potent integrin receptor inhibitor from the venoms of Dendroaspis viridis and D. jamesonii","volume":"21","author":"Williams","year":"1993","journal-title":"Biochem. Soc. Trans."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1002\/pro.2169","article-title":"Dynamics and functional differences between dendroaspin and rhodostomin: Insights into protein scaffolds in integrin recognition","volume":"21","author":"Cheng","year":"2012","journal-title":"Protein Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"19827","DOI":"10.1016\/S0021-9258(19)77710-2","article-title":"Echistatin. A potent platelet aggregation inhibitor from the venom of the viper, Echis carinatus","volume":"263","author":"Gan","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"39805","DOI":"10.1038\/srep39805","article-title":"A Comprehensive Evaluation of the Activity and Selectivity Profile of Ligands for RGD-binding Integrins","volume":"7","author":"Kapp","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1042\/bj2700149","article-title":"Ligands to the platelet fibrinogen receptor glycoprotein IIb-IIIa do not affect agonist-induced second messengers Ca2+ or cyclic AMP","volume":"270","author":"Williams","year":"1990","journal-title":"Biochem. J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1006\/jmbi.1993.1439","article-title":"The nuclear magnetic resonance solution structure of flavoridin, an antagonist of the platelet GP IIb-IIIa receptor","volume":"232","author":"Senn","year":"1993","journal-title":"J. Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0300-9084(96)82187-0","article-title":"Biochemical characterization of a new disintegrin, flavostatin, isolated from Trimeresurus flavoviridis venom","volume":"78","author":"Kawasaki","year":"1996","journal-title":"Biochimie"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0003-9861(92)90087-D","article-title":"An antiplatelet peptide, gabonin, from Bitis gabonica snake venom","volume":"298","author":"Huang","year":"1992","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/0006-2952(91)90256-5","article-title":"Halysin, an antiplatelet Arg-Gly-Asp-containing snake venom peptide, as fibrinogen receptor antagonist","volume":"42","author":"Huang","year":"1991","journal-title":"Biochem. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s00239-006-0161-4","article-title":"Loss of Introns Along the Evolutionary Diversification Pathway of Snake Venom Disintegrins Evidenced by Sequence Analysis of Genomic DNA from Macrovipera lebetina transmediterranea and Echis ocellatus","volume":"64","author":"Bazaa","year":"2006","journal-title":"J. Mol. Evol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.toxicon.2010.10.013","article-title":"Insularin, a disintegrin from Bothrops insularis venom: Inhibition of platelet aggregation and endothelial cell adhesion by the native and recombinant GST-insularin proteins","volume":"57","author":"Butera","year":"2011","journal-title":"Toxicon"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.abb.2008.11.023","article-title":"Integrin inhibitors from snake venom: Exploring the relationship between the structure and activity of RGD-peptides","volume":"482","author":"Wermelinger","year":"2009","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.cbpc.2004.06.012","article-title":"A novel disintegrin, jerdonatin, inhibits platelet aggregation and sperm\u2013egg binding","volume":"139","author":"Zhou","year":"2004","journal-title":"Comp. Biochem. Physiol. Part B Biochem. Mol. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1093\/oxfordjournals.jbchem.a002898","article-title":"Comparative biochemistry of disintegrins isolated from snake venom: Consideration of the taxonomy and geographical distribution of snakes in the genus Echis","volume":"129","author":"Okuda","year":"2001","journal-title":"J. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.taap.2005.07.004","article-title":"Isolation and characterization of two disintegrins inhibiting ADP-induced human platelet aggregation from the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake)","volume":"212","author":"Russell","year":"2006","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_75","first-page":"86","article-title":"Morulustatin, A. Disintegrin that Inhibits ADP-Induced Platelet Aggregation, Isolated from the Mexican Tamaulipan Rock Rattlesnake (Crotalus lepidus morulus)","volume":"26","author":"Borja","year":"2016","journal-title":"Rev. Cient."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3325\/cmj.2017.58.118","article-title":"Antiplatelet and anti-proliferative action of disintegrin from Echis multisquamatis snake venom","volume":"58","author":"Chernyshenko","year":"2017","journal-title":"Croat. Med. J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/oxfordjournals.jbchem.a003000","article-title":"Purification and characterization of a new RGD\/KGD-containing dimeric disintegrin, piscivostatin, from the venom of Agkistrodon piscivorus piscivorus: The unique effect of piscivostatin on platelet aggregation","volume":"130","author":"Okuda","year":"2001","journal-title":"J. Biochem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.toxicon.2011.12.002","article-title":"Recombinant rubistatin (r-Rub), an MVD disintegrin, inhibits cell migration and proliferation, and is a strong apoptotic inducer of the human melanoma cell line SK-Mel-28","volume":"59","author":"Carey","year":"2012","journal-title":"Toxicon"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0049-3848(98)00053-X","article-title":"Purification and molecular cloning of a platelet aggregation inhibitor from the snake (Agkistrodon halys brevicaudus) venom","volume":"91","author":"Kang","year":"1998","journal-title":"Thromb. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/S1016-8478(23)13468-6","article-title":"Cloning and characterization of novel disintegrins from Agkistrodon halys venom","volume":"8","author":"Park","year":"1998","journal-title":"Mol. Cells"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0049-3848(01)00416-9","article-title":"Snake venom disintegrin, saxatilin, inhibits platelet aggregation, human umbilical vein endothelial cell proliferation, and smooth muscle cell migration","volume":"105","author":"Hong","year":"2002","journal-title":"Thromb. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.jmb.2004.06.048","article-title":"Crystal Structure of Schistatin, a Disintegrin Homodimer from Saw-scaled Viper (Echis carinatus) at 2.5 \u00c5 Resolution","volume":"341","author":"Bilgrami","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_83","first-page":"328","article-title":"Triflavin, an antiplatelet Arg-Gly-Asp-containing peptide, is a specific antagonist of platelet membrane glycoprotein IIb-IIIa complex","volume":"109","author":"Huang","year":"1991","journal-title":"J. Biochem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"16157","DOI":"10.1016\/S0021-9258(18)47710-1","article-title":"Trigramin. A low molecular weight peptide inhibiting fibrinogen interaction with platelet receptors expressed on glycoprotein IIb-IIIa complex","volume":"262","author":"Huang","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/0014-4827(88)90346-1","article-title":"Trigramin, an RGD-containing peptide from snake venom, inhibits cell-substratum adhesion of human melanoma cells","volume":"179","author":"Knudsen","year":"1988","journal-title":"Exp. Cell Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s00210-016-1233-7","article-title":"The disintegrin, trimucrin, suppresses LPS-induced activation of phagocytes primarily through blockade of NF-\u03baB and MAPK activation","volume":"389","author":"Hung","year":"2016","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1093\/oxfordjournals.jbchem.a022264","article-title":"Ussuristatin 2, a novel KGD-bearing disintegrin from Agkistrodon ussuriensis venom","volume":"125","author":"Oshikawa","year":"1999","journal-title":"J. Biochem."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Minea, R.O., Helchowski, C.M., Zidovetzki, S.J., Costa, F.K., Swenson, S.D., and Markland, F.S. (2010). Vicrostatin\u2014An anti-invasive multi-integrin targeting chimeric disintegrin with tumor anti-angiogenic and pro-apoptotic activities. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010929"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"6702","DOI":"10.1016\/S0021-9258(17)37432-X","article-title":"Disagregin is a fibrinogen receptor antagonist lacking the Arg-Gly-Asp sequence from the tick, Ornithodoros moubata","volume":"269","author":"Karczewski","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.ibmb.2005.05.007","article-title":"The transcriptome of the salivary glands of the female western black-legged tick Ixodes pacificus (Acari: Ixodidae)","volume":"35","author":"Francischetti","year":"2005","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ibmb.2007.09.002","article-title":"Characterization of anti-hemostatic factors in the argasid, Argas monolakensis: Implications for the evolution of blood-feeding in the soft tick family","volume":"38","author":"Mans","year":"2008","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"21371","DOI":"10.1074\/jbc.M112060200","article-title":"Savignygrin, a platelet aggregation inhibitor from the soft tick Ornithodoros savignyi, presents the RGD integrin recognition motif on the Kunitz-BPTI fold","volume":"277","author":"Mans","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"17785","DOI":"10.1074\/jbc.271.30.17785","article-title":"Variabilin, a novel RGD-containing antagonist of glycoprotein IIb-IIIa and platelet aggregation inhibitor from the hard tick Dermacentor variabilis","volume":"271","author":"Wang","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"10143","DOI":"10.1016\/S0021-9258(19)38791-5","article-title":"Decorsin. A potent glycoprotein IIb-IIIa antagonist and platelet aggregation inhibitor from the leech Macrobdella decora","volume":"265","author":"Seymour","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1111\/j.1432-1033.1991.tb16472.x","article-title":"Ornatins: Potent glycoprotein IIb-IIIa antagonists and platelet aggregation inhibitors from the leech Placobdella ornata","volume":"202","author":"Mazur","year":"1991","journal-title":"Eur. J. Biochem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0166-6851(03)00121-X","article-title":"Isolation and molecular cloning of a secreted hookworm platelet inhibitor from adult Ancylostoma caninum","volume":"129","author":"Jones","year":"2003","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1086\/314724","article-title":"The hookworm platelet inhibitor: Functional blockade of integrins GPIIb\/IIIa (alphaIIbbeta3) and GPIa\/IIa (alpha2beta1) inhibits platelet aggregation and adhesion in vitro","volume":"179","author":"Chadderdon","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1074\/mcp.M900186-MCP200","article-title":"Anti-thrombosis Repertoire of Blood-feeding Horsefly Salivary Glands","volume":"8","author":"Ma","year":"2009","journal-title":"Mol. Cell. Proteom."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1160\/TH11-01-0029","article-title":"A novel family of RGD-containing disintegrins (Tablysin-15) from the salivary gland of the horsefly Tabanus yao targets \u03b1IIb\u03b23 or \u03b1V\u03b23 and inhibits platelet aggregation and angiogenesis","volume":"105","author":"Liu","year":"2011","journal-title":"Thromb. Haemost."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1042\/bj3170817","article-title":"Immunological characterization of eristostatin and echistatin binding sites on alpha IIb beta 3 and alpha V beta 3 integrins","volume":"317","author":"Marcinkiewicz","year":"1996","journal-title":"Biochem. J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/rth2.12466","article-title":"Inhibition of platelet adhesion, thrombus formation, and fibrin formation by a potent alphaIIbbeta3 integrin inhibitor from ticks","volume":"5","author":"Nagy","year":"2021","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1006\/prep.1993.1036","article-title":"Expression, purification, and characterization of recombinant ornatin E, a potent glycoprotein IIb-IIIa antagonist","volume":"4","author":"Mazur","year":"1993","journal-title":"Protein Expr. Purif."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1023\/B:THRO.0000003308.63022.8d","article-title":"Comparative pharmacology of GP IIb\/IIIa antagonists","volume":"15","author":"Schror","year":"2003","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1161\/01.CIR.97.17.1680","article-title":"Pharmacodynamic profile of short-term abciximab treatment demonstrates prolonged platelet inhibition with gradual recovery from GP IIb\/IIIa receptor blockade","volume":"97","author":"Mascelli","year":"1998","journal-title":"Circulation"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1161\/01.RES.0000232317.84122.0c","article-title":"Conformation-specific blockade of the integrin GPIIb\/IIIa: A novel antiplatelet strategy that selectively targets activated platelets","volume":"99","author":"Schwarz","year":"2006","journal-title":"Circ. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"45","DOI":"10.5830\/CVJA-2018-063","article-title":"Intracoronary or intravenous abciximab after aspiration thrombectomy in patients with STEMI undergoing primary percutaneous coronary intervention","volume":"30","author":"Bedjaoui","year":"2019","journal-title":"Cardiovasc. J. Afr."},{"key":"ref_107","unstructured":"Stoffer, K., Bistas, K.G., Reddy, V., and Shah, S. (2020). Abciximab, StatPearls."},{"key":"ref_108","unstructured":"(FDA) US (2021, February 08). FDA Drug Shortages, Available online: https:\/\/www.accessdata.fda.gov\/scripts\/drugshortages\/dsp_ActiveIngredientDetails.cfm?AI=Abciximab%20(ReoPro)%20Injection&st=c&tab=tabs-1."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"11B","DOI":"10.1016\/S0002-9149(97)00572-9","article-title":"Clinical pharmacology of eptifibatide","volume":"80","author":"Phillips","year":"1997","journal-title":"Am. J. Cardiol."},{"key":"ref_110","first-page":"192","article-title":"Chemical structures and mode of action of intravenous glycoprotein IIb\/IIIa receptor blockers: A review","volume":"13","author":"Hashemzadeh","year":"2008","journal-title":"Exp. Clin. Cardiol."},{"key":"ref_111","first-page":"29","article-title":"Abciximab: A reappraisal of its use in coronary care","volume":"2","author":"Valgimigli","year":"2008","journal-title":"Biologics"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1208\/s12248-014-9687-3","article-title":"Strategic approaches to optimizing peptide ADME properties","volume":"17","author":"Di","year":"2015","journal-title":"AAPS J."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Gang, D., Kim, D.W., and Park, H.S. (2018). Cyclic Peptides: Promising Scaffolds for Biopharmaceuticals. Genes, 9.","DOI":"10.3390\/genes9110557"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1161\/hc3101.092199","article-title":"Eptifibatide and 7E3, but not tirofiban, inhibit alpha(v)beta integrin-mediated binding of smooth muscle cells to thrombospondin and prothrombin","volume":"104","author":"Lele","year":"2001","journal-title":"Circulation"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1067\/mhj.2000.103742","article-title":"Clinical challenges of platelet glycoprotein IIb\/IIIa receptor inhibitor therapy: Bleeding, reversal, thrombocytopenia, and retreatment","volume":"139","author":"Tcheng","year":"2000","journal-title":"Am. Heart J."},{"key":"ref_116","unstructured":"Bansal, A.B., Sattar, Y., and Jamil, R.T. (2020). Eptifibatide, StatPearls."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"The PURSUIT Trial Investigators (1998). Inhibition of platelet glycoprotein IIb\/IIIa with eptifibatide in patients with acute coronary syndromes. N. Engl. J. Med., 339, 436\u2013443.","DOI":"10.1056\/NEJM199808133390704"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jacc.2004.03.042","article-title":"The additive value of tirofiban administered with the high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: The ADVANCE Trial","volume":"44","author":"Valgimigli","year":"2004","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/0002-8703(95)90305-4","article-title":"Enhancing safety and outcomes with the newer antithrombotic and antiplatelet agents","volume":"130","author":"Tcheng","year":"1995","journal-title":"Am. Heart J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1111\/j.1538-7836.2006.02202.x","article-title":"The potential role of antiplatelet agents in modulating inflammatory markers in atherothrombosis","volume":"4","author":"Yeh","year":"2006","journal-title":"J. Thromb. Haemost."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/med.1007","article-title":"Orbofiban: An orally active GPIIb\/IIIa platelet receptor antagonist","volume":"21","author":"Nicholson","year":"2001","journal-title":"Med. Res. Rev."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1161\/01.CIR.102.2.149","article-title":"Oral Glycoprotein IIb\/IIIa Inhibition With Orbofiban in Patients With Unstable Coronary Syndromes (OPUS-TIMI 16) Trial","volume":"102","author":"Cannon","year":"2000","journal-title":"Circulation"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0002-9149(99)00778-X","article-title":"Increased platelet reactivity in patients given orbofiban after an acute coronary syndrome: An OPUS-TIMI 16 substudy. Orbofiban in Patients with Unstable coronary syndromes. Thrombolysis In Myocardial Infarction","volume":"85","author":"Holmes","year":"2000","journal-title":"Am. J. Cardiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1023\/A:1025335718142","article-title":"Role of oral blockade of platelet glycoprotein IIb\/IIIa on neutrophil activation in patients with acute coronary syndromes","volume":"17","author":"Serrano","year":"2003","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2165\/00003495-199957020-00012","article-title":"Sibrafiban","volume":"57","author":"Dooley","year":"1999","journal-title":"Drugs"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/S0002-8703(99)70104-3","article-title":"Long-term oral platelet glycoprotein IIb\/IIIa receptor antagonism with sibrafiban after acute coronary syndromes: Study design of the sibrafiban versus aspirin to yield maximum protection from ischemic heart events post-acute coronary syndromes (SYMPHONY) trial. Symphony Steering Committee","volume":"138","author":"Newby","year":"1999","journal-title":"Am. Heart J."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"The SYMPHONY Investigators (2000). Comparison of sibrafiban with aspirin for prevention of cardiovascular events after acute coronary syndromes: A randomised trial. Lancet, 355, 337\u2013345.","DOI":"10.1016\/S0140-6736(99)11179-6"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/j.1527-3466.2001.tb00059.x","article-title":"Xemilofiban\/orbofiban: Insight into drug development","volume":"19","author":"Anders","year":"2001","journal-title":"Cardiovasc. Drug Rev."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1056\/NEJM200005043421803","article-title":"Long-Term Treatment with a Platelet Glycoprotein-Receptor Antagonist after Percutaneous Coronary Revascularization","volume":"342","author":"Serruys","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1517\/13543784.9.11.2673","article-title":"Lotrafiban: An oral platelet glycoprotein IIb\/IIIa blocker","volume":"9","author":"Liu","year":"2000","journal-title":"Exp. Opin. Investig. Drugs"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1161\/01.CIR.0000084501.48570.F6","article-title":"Randomized, Double-Blind, Placebo-Controlled, International Trial of the Oral IIb\/IIIa Antagonist Lotrafiban in Coronary and Cerebrovascular Disease","volume":"108","author":"Topol","year":"2003","journal-title":"Circulation"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1161\/01.ATV.19.10.2535","article-title":"Intravenous and oral antithrombotic efficacy of the novel platelet GPIIb\/IIIa antagonist roxifiban (DMP754) and its free acid form, XV459","volume":"19","author":"Mousa","year":"1999","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_133","first-page":"1277","article-title":"Antiplatelet efficacy of XV459, a novel nonpeptide platelet GPIIb\/IIIa antagonist: Comparative platelet binding profiles with c7E3","volume":"286","author":"Mousa","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0002-8703(03)00186-8","article-title":"Roxifiban Oral Compound Kinetics Evaluation Trial IPS. Effects of roxifiban on platelet aggregation and major receptor expression in patients with coronary artery disease for the Roxifiban Oral Compound Kinetics Evaluation Trial-I (ROCKET-I Platelet Substudy)","volume":"146","author":"Serebruany","year":"2003","journal-title":"Am. Heart J."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1160\/TH11-10-0727","article-title":"GPIIb\/IIIa inhibitors: From bench to bedside and back to bench again","volume":"107","author":"Armstrong","year":"2012","journal-title":"Thromb. Haemost."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1161\/01.CIR.0000127867.41621.85","article-title":"Thrombocytopenia Caused by Abciximab or Tirofiban and Its Association With Clinical Outcome in Patients Undergoing Coronary Stenting","volume":"109","author":"Merlini","year":"2004","journal-title":"Circulation"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1098\/rstb.2008.0157","article-title":"Immune defence, parasite evasion strategies and their relevance for \u2018macroscopic phenomena\u2019 such as virulence","volume":"364","year":"2009","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Kuo, Y.J., Chung, C.H., Pan, T.Y., Chuang, W.J., and Huang, T.F. (2019). A Novel alphaIIbbeta3 Antagonist from Snake Venom Prevents Thrombosis without Causing Bleeding. Toxins, 12.","DOI":"10.3390\/toxins12010011"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1097\/00000542-200205000-00029","article-title":"Platelet glycoprotein IIb\/IIIa antagonists: Pharmacology and clinical developments","volume":"96","author":"Kam","year":"2002","journal-title":"Anesthesiology."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0002-8703(98)70238-8","article-title":"Oral inhibitors of platelet membrane receptor glycoprotein IIb\/IIIa in clinical cardiology: Issues and opportunities","volume":"135","author":"Theroux","year":"1998","journal-title":"Am. Heart J."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/rth2.12080","article-title":"The coagulation system in atherothrombosis: Implications for new therapeutic strategies","volume":"2","author":"Olie","year":"2018","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/S0140-6736(18)31924-X","article-title":"Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): A randomised, double-blind, placebo-controlled trial","volume":"392","author":"Gaziano","year":"2018","journal-title":"Lancet"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nrcardio.2017.206","article-title":"Current and future antiplatelet therapies: Emphasis on preserving haemostasis","volume":"15","author":"McFadyen","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1093\/cvr\/cvz070","article-title":"Platelets in cardiac ischaemia\/reperfusion injury: A promising therapeutic target","volume":"115","author":"Ziegler","year":"2019","journal-title":"Cardiovasc. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3366\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:41:04Z","timestamp":1760161264000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,25]]},"references-count":144,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22073366"],"URL":"https:\/\/doi.org\/10.3390\/ijms22073366","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,25]]}}}