(Circulation. 1998;97:5-9.)
© 1998 American Heart Association, Inc.
Monitoring Platelet GP IIb/IIIa Antagonist Therapy
Barry S. Coller, MD
From the Department of Medicine, Mount Sinai School of Medicine, New
York, NY.
Correspondence to Barry S. Coller, MD, Department of Medicine, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029. E-mail bcoller@smtplink.mssm.edu
Key Words: angioplasty • thrombosis • glycoproteins • receptors • platelet aggregation inhibitors
Platelet
GP IIb/IIIa receptor antagonist therapy with abciximab
(ReoPro), the Fab fragment of a mouse/human chimeric version of the
murine 7E3 antibody, is currently used to prevent ischemic
complications of percutaneous coronary
interventions in select cases, and the efficacy and safety of abciximab
for other related indications are under
study.1 2 3 4 A number of low-molecular-weight GP
IIb/IIIa antagonists patterned on the
arginine-glycine-aspartic acid (RGD) cell recognition sequence have
also shown benefit in the prevention and treatment of ischemic
thrombotic coronary artery disease and currently are in
advanced stages of development and
approval.1 2 3 4
The ease with which samples of blood platelets can be
obtained, the availability of well-characterized methods for assessing
platelet function, and the development of a radiolabeled antibody
assay to assess the percentage of GP IIb/IIIa receptors blocked by 7E3
permitted the incorporation into the preclinical and early clinical
trials of 7E3 extensive correlative studies of the antithrombotic
effects of 7E3 compared with its effects on bleeding time, platelet
aggregation, and GP IIb/IIIa receptor
blockade.5 6 7 8 These studies provided a framework
for deciding on a dosing schedule for the first phase III study
(EPIC).9 Similar studies have been reported with
some of the other GP IIb/IIIa
antagonists.10 11 12 The more rapid GP
IIb/IIIa off-rates of many of the low-molecular-weight compounds
compared with 7E3 have made it technically more difficult to directly
assess GP IIb/IIIa receptor blockade with these agents, but binding
studies have been reported that used fluorescent compounds in
conjunction with flow cytometry, radiolabeled compounds, or the
expression of ligand-induced binding . . . [Full Text of this Article]
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