This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nurden, A. T. Articles by Nurden, P. Search for Related Content PubMed PubMed Citation Articles by Nurden, A. T. Articles by Nurden, P. Related Collections Cardiovascular Pharmacology Cell signalling/signal transduction Platelets

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2835.)
© 1999 American Heart Association, Inc.

Brief Reviews

Platelet Glycoprotein IIb/IIIa Inhibitors

Basic and Clinical Aspects

Alan T. Nurden; Christel Poujol; Catherine Durrieu-Jais; Paquita Nurden

From the UMR 5533 CNRS and the Unité des Soins Intensifs (C.D.-J.), Institut Fédératif de Recherche "Cur-Vaisseaux-Thrombose," Hôpital Cardiologique, Pessac, France.

Correspondence to Alan T. Nurden, Director, UMR 5533 CNRS, Hôpital Cardiologique, 33604 Pessac, France. E-mail Alan.Nurden@cnrshl.u-bordeaux2.fr

Key Words: glycoproteins • abciximab • platelet aggregation • antithrombotic drugs

	Introduction

 
Glycoprotein IIb/IIIa (GPIIb-IIIa) complexes (integrin _IIbß₃) mediate platelet aggregation by binding fibrinogen or von Willebrand factor (vWF), protein cofactors that form bridges between adjacent platelets. The cross-linked adhesive proteins assemble platelets into the aggregate. Agents that block the function of the GPIIb-IIIa complex of platelets constitute a powerful new generation of antithrombotic drugs.¹ Among the short- and long-term aims of such drugs are (1) to provide immediate relief in the case of ongoing arterial thrombosis and (2) to eliminate excessive platelet reactivity in diseased vessels so that occlusive thrombi and restenosis do not occur, while allowing sufficient hemostasis to prevent spontaneous bleeding. It should be emphasized that stenosis and partial occlusion are both prothrombotic, with increased shear stress promoting platelet activation. Under these conditions, vWF plays a major role in the mediation of thrombus formation, interacting with GPIIb-IIIa and the adhesion receptor GPIb.² Otherwise, fibrinogen is the major cofactor of platelet aggregation, essentially binding through a dodecapeptide sequence (aa400 to aa411) present at the carboxy terminus of each chain. Binding of vWF and other adhesive proteins, such as fibronectin, to GPIIb-IIIa is mediated by the Arg-Gly-Asp (RGD) sequence, a universal mediator of cellular interactions with the extracellular matrix.^{1 2 3} Anti–GPIIb-IIIa drugs block this final step of the platelet aggregation process. They also block the "outside-in" signaling that follows the binding of adhesive proteins to activated GPIIb-IIIa and the onset of platelet aggregation.³ This signaling may promote events such as secretion, clot retraction, and the expression of procoagulant activity; therefore, its . . . [Full Text of this Article]

This article has been cited by other articles:

				L. T. Newsome, R. S. Weller, J. C. Gerancher, M. A. Kutcher, and R. L. Royster Coronary Artery Stents: II. Perioperative Considerations and Management Anesth. Analg., August 1, 2008; 107(2): 570 - 590. [Abstract] [Full Text] [PDF]

				C. Patrono, C. Baigent, J. Hirsh, and G. Roth Antiplatelet Drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 199S - 233S. [Abstract] [Full Text] [PDF]

				C. Patrono, B. Coller, G. A. FitzGerald, J. Hirsh, and G. Roth Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 234S - 264S. [Abstract] [Full Text] [PDF]

				W. B. Batchelor, T. R. Tolleson, Y. Huang, R. L. Larsen, R. M. Mantell, P. Dillard, M. Davidian, D. Zhang, W. J. Cantor, M. H. Sketch Jr, et al. Randomized COMparison of Platelet Inhibition With Abciximab, TiRofiban and Eptifibatide During Percutaneous Coronary Intervention in Acute Coronary Syndromes: The COMPARE Trial Circulation, September 17, 2002; 106(12): 1470 - 1476. [Abstract] [Full Text] [PDF]

				J. T. Billheimer, I. B. Dicker, R. Wynn, J. D. Bradley, D. A. Cromley, H. E. Godonis, L. C. Grimminger, B. He, C. J. Kieras, D. L. Pedicord, et al. Evidence that thrombocytopenia observed in humans treated with orally bioavailable glycoprotein IIb/IIIa antagonists is immune mediated Blood, May 15, 2002; 99(10): 3540 - 3546. [Abstract] [Full Text] [PDF]

				M.-J. Jacobin, J. Laroche-Traineau, M. Little, A. Keller, K. Peter, M. Welschof, A. Nurden, and G. Clofent-Sanchez Human IgG Monoclonal Anti-{alpha}IIb{beta}3-Binding Fragments Derived from Immunized Donors Using Phage Display J. Immunol., February 15, 2002; 168(4): 2035 - 2045. [Abstract] [Full Text] [PDF]

				F.-J. Neumann, W. Hochholzer, G. Pogatsa-Murray, A. Schomig, and M. Gawaz Antiplatelet effects of abciximab, tirofiban and eptifibatide in patients undergoing coronary stenting J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1323 - 1328. [Abstract] [Full Text] [PDF]

				C. Patrono, B. Coller, J. E. Dalen, G. A. FitzGerald, V. Fuster, M. Gent, J. Hirsh, and G. Roth Platelet-Active Drugs : The Relationships Among Dose, Effectiveness, and Side Effects Chest, January 1, 2001; 119 (2009): 39S - 63S. [Full Text] [PDF]

				D. A. Triplett Coagulation and Bleeding Disorders: Review and Update Clin. Chem., August 1, 2000; 46(8): 1260 - 1269. [Abstract] [Full Text] [PDF]