Treatment with a GPIIb/IIIa Antagonist Inhibits Thrombin Generation in Platelet Rich Plasma from Patients

I. M. L. W. Keularts; S. Béguin; C. de Zwaan; H. C. Hemker

doi:10.1055/s-0037-1615213

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 80(03): 370-371
DOI: 10.1055/s-0037-1615213

Rapid Communications

Schattauer GmbH

Treatment with a GPIIb/IIIa Antagonist Inhibits Thrombin Generation in Platelet Rich Plasma from Patients

Authors

I. M. L. W. Keularts

¹From the Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, Maastricht, The Netherlands
S. Béguin

¹From the Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, Maastricht, The Netherlands
C. de Zwaan

¹Department of Cardiology, Academic Hospital, Maastricht, Maastricht, The Netherlands
H. C. Hemker

¹From the Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, Maastricht, The Netherlands

Abstract

Summary

Infusion of the GPIIb/IIIa-inhibitor MK383 inhibits thrombin generation in platelet rich plasma by interfering with the production of platelet procoagulant phospholipid exposure. The effect is similar to that of 0.2 U/ml of heparin. Heparin infusion, well known to inhibit thrombin generation by fostering antithrombin activity, inhibits the formation of platelet-derived procoagulant microparticles, probably by decreasing the formation of free thrombin, which, under our circumstances, is the main platelet activator.

Full Text

References

References
1 Reverter JC, Béguin S, Kessels H, Kumar R, Hemker HC, Coller BS. Inhibition of platelet mediated tissue induced thrombin generation by mouse/human chimeric 7E3 antibody: Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and “Clinical Restenosis”. J Clin Invest 1996; 98: 863-74.
2 Pedicord DL, Mousa SA, Dicker IB. Platelet GPIIb/IIIa antagonists inhibit platelet procoagulant activity. Thromb Haemost,. Supplement 1997 p. 660 , Abstract PS-2693.
3 Herault JP, Peyrou V, Savi P, Bernat A, Herbert JM. Effect of SR121566A, a potent GPIIb/IIIa antagonist on platelet-mediated thrombin generation in vitro and in vivo. Thromb Haemost 1998; 79: 383-8.
4 Gould RJ, Chang CTC, Lynch RJ. et al. MK-0383 is a potent non-peptide mimic of RGD that inhibits glycoprotein IIb/IIIa. Thromb Haemost 1993; 69:: 976.
5 Barrett JS, Murphy G, Peerlinck K, De Lepeleire I, Gould RJ, Panebianco D, Hand E, Deckmyn H, Vermylen J, Arnout J. Pharmacokinetics and pharmacodynamics of MK-383, a selective non-peptide platelet glycoproteinIIb/IIIa receptor antagonist, in healthy men. Clin Pharmacol & Ther 1994; 56: 377-88.
6 Hemker HC, Willems GM, Béguin S. A computer assisted method to obtain the prothrombin activation velocity in whole plasma independent of thrombin decay processes. Thromb Haemost 1986; 56: 9-17.
7 Béguin S, Lindhout T, Hemker HC. The effect of trace amounts of tissue factor on thrombin generation in PRP, its inhibition by heparin. Thromb Haemost 1989; 61: 25-9.
8 Wagenvoord RJ, Hendrix HH, Hu Kai, Hemker HC. A chromogenic test to determine the procoagulant phospholipids in platelet rich plasma and whole blood. Thromb Haemost 1994; 72: 582-7.
9 Bevers EM, Comfurius P, van Rijn JLML, Hemker HC, Zwaal RFA. Generation of prothrombin converting activity and the exposure of phosphatidylserine at the outer surface of platelets. Eur J Biochem 1982; 122: 429-36.
10 Kessels H, Béguin S, Andree H, Hemker HC. Measurement of thrombin generation whole blood – The effect of heparin and aspirin. Thromb Haemost 1994; 72: 78-83.
11 Sixty-Plus Reinfarction Study Research Group.. A double blind trial to assess long-term oral anticoagulant therapy in elderly patients after myocar-dial infarction. Lancet 1980; 2: 989-94.
12 Neri-Serneri GG, Rovelli F, Gensine GF, Pirelli S, Carnovali M, Fortini A. Effectiveness of low-dose heparin in prevention of myocardial reinfarction. Lancet 1987; 25: 937-42.