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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:607.)
© 2000 American Heart Association, Inc.

Brief Review

Platelet Glycoprotein IIb/IIIa Receptors and Glanzmann’s Thrombasthenia

Deborah L. French; Uri Seligsohn

From the Mount Sinai School of Medicine (D.L.F.), New York, NY, and The Chaim Sheba Medical Center (U.S.), Tel-Hashomer, Israel.

Correspondence to Deborah L. French, PhD, Box 1079 Hematology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029. E-mail dfrench@smtplink.mssm.edu

Key Words: platelets • integrins • Glanzmann’s thrombasthenia

	Introduction

 
Platelet aggregation and fibrin formation are essential for the maintenance of normal hemostasis, a system designed to act quickly and effectively to arrest hemorrhage. This system is also triggered by pathogenic events, such as the rupture of an atherosclerotic plaque, which can lead to thrombotic vaso-occlusion, ischemia, and infarction. Platelets are a major contributor to these damaging and life-threatening thrombotic phenomena because of their adhesive properties, which result in the release of soluble mediators, platelet aggregation, and enhancement of thrombin generation.¹ The platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptor is a key component in the pathway to platelet aggregation; consequently, this receptor has become the target for therapeutic intervention. A paradigm of this antiplatelet treatment modality is found naturally in the inherited disorder Glanzmann’s thrombasthenia. A key feature of this disease is that patients present with mucocutaneous bleeding but only rarely demonstrate spontaneous central nervous system hemorrhage,² a feared complication of anticoagulant and antiplatelet therapy. All of the mutations that have been identified in patients with Glanzmann’s thrombasthenia result in a functional deficiency of GPIIb/IIIa receptors,^{2 3} and a hallmark of this disease is the absence of agonist-induced platelet aggregation. The molecular characterization of mutations causing Glanzmann’s thrombasthenia has provided a wealth of information on structure-function relations of the GPIIb/IIIa receptor. This review will briefly summarize those mutations that affect ligand-binding domains and receptor activation and present them in the context of predicted structures. More comprehensive coverage can be found in reviews discussing the structure and function of the GPIIb/IIIa receptor complex^{4 5} and . . . [Full Text of this Article]

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