| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Cardiovascular Medicine, University Hospital,
Queen's Medical Centre, Nottingham, UK.
Correspondence to Dr R.F. Storey, BSc, BM, MRCP, Research Registrar in Cardiovascular Medicine, Department of Cardiovascular Medicine, University Hospital, Queen's Medical Centre, Nottingham, NG7 2UH, UK. E-mail mmxrfs{at}mmn1.nottingham.ac.uk
Background—Citrated
platelet-rich plasma (PRP) turbidimetry is used for assessing
pharmacodynamic effects of glycoprotein (GP) IIb/IIIa
antagonists in clinical trials. However, citrate can
enhance the potency of at least eptifibatide (Integrilin), and
turbidimetry is insensitive to microaggregate formation. We compared
PRP turbidimetry, as a measure of macroaggregate formation, with
single-platelet counting in both whole blood and PRP as a measure
of microaggregate formation, using both citrate and hirudin
anticoagulation.
Methods and Results—Three GP IIb/IIIa antagonists,
eptifibatide, MK-0852, and GR144053, were compared in PRP
(turbidimetry) and whole blood (platelet counting with an Ultra-Flo
100 Platelet Counter), with ADP and collagen used as agonists.
Compared with hirudin, citrate enhanced the potency of eptifibatide by
up to 4-fold in both PRP and whole blood
(P<0.0005), modestly enhanced MK-0852
potency (P=0.001), and had no effect on GR144053.
Potency measured in PRP was 2- to 3-fold greater compared with whole
blood for MK-0852 and GR144053 but 3- to 4-fold greater for
eptifibatide. Simultaneous turbidimetry and platelet
counting performed in PRP indicated that this is because GP IIb/IIIa
antagonists are more potent inhibitors of in
vitro macroaggregation than microaggregation, this effect being greater
for eptifibatide in hirudinized PRP compared with GR144053
(P=0.032).
Conclusions—GP IIb/IIIa antagonist potency is
variably enhanced by citrate. Macroaggregation is inhibited more
effectively than microaggregation, most markedly in the case of
eptifibatide in hirudinized blood. These observations have implications
for the interpretation and comparison of pharmacodynamic assays and
possibly for the risk/benefit ratio of different agents.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Differential Effects of Glycoprotein IIb/IIIa Antagonists on Platelet Microaggregate and Macroaggregate Formation and Effect of Anticoagulant on Antagonist Potency
Implications for Assay Methodology and Comparison of Different Antagonists
Key Words: glycoproteins • calcium • platelet aggregation inhibitors
This article has been cited by other articles:
 |
|
 |
|
  I. A. Jagroop and D. P. Mikhailidis The Effect of Tirofiban on Fibrinogen/Agonist-Induced Platelet Shape Change and Aggregation Clinical and Applied Thrombosis/Hemostasis, July 1, 2008; 14(3): 295 - 302. [Abstract] [PDF]
|
|
|
|
 |
|
 R. F. Storey Variability of response to antiplatelet therapy Eur. Heart J. Suppl., January 1, 2008; 10(suppl_A): A21 - A27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Reiter, F. Mayr, H. Blazicek, E. Galehr, P. Jilma-Stohlawetz, H. Domanovits, and B. Jilma Desmopressin antagonizes the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors and aspirin Blood, December 15, 2003; 102(13): 4594 - 4599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Poullis, R C Landis, and K M Taylor Aprotinin: is it prothrombotic? Perfusion, September 1, 2001; 16(5): 401 - 409. [Abstract] [PDF]
|
|
|
|
 |
|
 B. E. Tardiff, L. K. Jennings, R. A. Harrington, D. Gretler, R. F. Potthoff, D. A. Vorchheimer, P. R. Eisenberg, A. M. Lincoff, M. Labinaz, D. M. Joseph, et al. Pharmacodynamics and Pharmacokinetics of Eptifibatide in Patients With Acute Coronary Syndromes: Prospective Analysis From PURSUIT Circulation, July 24, 2001; 104(4): 399 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Poullis, R. Manning, M. Laffan, D. O. Haskard, K. M. Taylor, and R. C. Landis The antithrombotic effect of aprotinin: actions mediated via the proteaseactivated receptor 1 J. Thorac. Cardiovasc. Surg., August 1, 2000; 120(2): 370 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. W. Muriithi, P. R. Belcher, S. P. Day, V. C. Menys, and D. J. Wheatley Heparin-induced platelet dysfunction and cardiopulmonary bypass Ann. Thorac. Surg., June 1, 2000; 69(6): 1827 - 1832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Nurden, C. Poujol, C. Durrieu-Jais, and P. Nurden Platelet Glycoprotein IIb/IIIa Inhibitors : Basic and Clinical Aspects Arterioscler Thromb Vasc Biol, December 1, 1999; 19(12): 2835 - 2840. [Full Text] [PDF]
|
|