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European Heart Journal Advance Access originally published online on May 24, 2009
European Heart Journal 2009 30(15):1831-1836; doi:10.1093/eurheartj/ehp186
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org

Regulation of PAR-1 in patients undergoing percutaneous coronary intervention: effects of unfractionated heparin and bivalirudin

Roza Badr Eslam1, Nina Reiter2, Alexandra Kaider3, Sabine Eichinger4, Irene M. Lang2,{dagger} and Simon Panzer2,*,{dagger}

1 Department of Internal Medicine 2, Division of Cardiology
2 Department of Blood Group Serology and Transfusion Medicine, Division of Blood Group Serology
3 Core Unit for Medical Statistics and Informatics, Section of Clinical Biometrics
4 Department of Internal Medicine I, Division of Haematology and Haemostaseology, Medical University of Vienna, Vienna, Austria

Received 19 November 2008; revised 6 March 2009; accepted 16 April 2009; online publish-ahead-of-print 24 May 2009.

* Corresponding author. Tel: +43 1 40400 5320, Fax: +43 1 40400 5321, Email: simon.panzer{at}meduniwien.ac.at

Aims: We examined the specific effects of unfractionated heparin and bivalirudin on thrombin-inducible platelet PAR-1 in patients undergoing percutaneous coronary intervention (PCI).

Methods and results: To simulate in vivo conditions that may precipitate a bleeding event, we added thrombin in vitro to blood samples from 89 patients who had been randomly assigned to receive heparin or bivalirudin for elective PCI and examined thrombin-inducible PAR-1 expression. Thrombin-inducible cleavage of PAR-1 was inhibited by heparin, but not affected by bivalirudin (P = 0.0001). Further, PAR-1 internalization was more effectively inhibited by heparin than bivalirudin (P = 0.002).

Conclusion: Heparin has stronger inhibitory effects on thrombin-dependent PAR-1 cleavage and internalization, thus providing a biological explanation for lower clinical bleeding rates with bivalirudin.

Key Words: Bivalirudin • Heparin • Platelets • PAR-1 • Thrombin • Percutaneous coronary intervention

{dagger} I.M.L. and S.P. contributed equally

This study was part of the doctorial thesis of NR at the Division of Blood Group Serology.


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