Blockade of GPIIb/IIIa by eptifibatide and tirofiban does not alter tissue factor induced thrombin generation in human endotoxemia

Ulla Derhaschnig; Christine Pachinger; Ingrid Schweeger-Exeli; Claudia Marsik; Bernd Jilma

doi:10.1160/TH03-04-0233

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(06): 1054-1060
DOI: 10.1160/TH03-04-0233

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Blockade of GPIIb/IIIa by eptifibatide and tirofiban does not alter tissue factor induced thrombin generation in human endotoxemia

Ulla Derhaschnig

¹Departments of Clinical Pharmacology, University of Vienna, Vienna, Austria

²Emergency Medicine, University of Vienna, Vienna, Austria

,

Christine Pachinger

¹Departments of Clinical Pharmacology, University of Vienna, Vienna, Austria

,

Ingrid Schweeger-Exeli

¹Departments of Clinical Pharmacology, University of Vienna, Vienna, Austria

,

Claudia Marsik

¹Departments of Clinical Pharmacology, University of Vienna, Vienna, Austria

⁴Institute for Medical Chemistry and Laboratory Diagnostics, University of Vienna, Vienna, Austria

,

Bernd Jilma

¹Departments of Clinical Pharmacology, University of Vienna, Vienna, Austria

³Pharmacology, University of Vienna, Vienna, Austria

› Author Affiliations

Abstract

Summary

Activated platelets facilitate thrombin generation by providing a catalytic surface on which coagulation activation occurs. The glycoprotein (GP) IIb/IIIa receptor might play a major role in this process as shown by in vitro and animal experiments. However, it is controversial whether the GPIIb/IIIa receptor facilitates tissue factor-induced thrombin generation in humans as well. We therefore investigated whether two clinically used GPIIb/IIIa antagonists (tirofiban and eptifibatide) may blunt TF-induced coagulation in humans.

Thirty male volunteers received 2 ng/kg endotoxin and standard doses of eptifibatide, tirofiban or placebo over 5 hours in a randomized, double-blind, placebo-controlled, double-dummy parallel-group trial. Markers of thrombin generation (prothrom-bin fragment 1+2, thrombin-antithrombin complexes), fibrinoly-sis (D-dimer, plasmin-antiplasmin complexes) as well as inflammatory markers (interleukin-6, tumor necrosis factor-α) were measured by enzyme linked immunoasssays, TF-mRNA expression was quantified by RT-PCR. Neither eptifibatide nor tirofiban influenced LPS-induced coagulation activation or fibrinolytic activity. Additionally, the increase of TNF-α and IL-6 was similar in all groups.

In conclusion, GPIIb/IIIa blockade with eptifibatide or tirofiban did not influence TF-induced coagulation activation in human low grade endotoxemia.

Keywords

Eptifibatide - tirofiban - endotoxemia - randomized controlled trial - coagulation activation

Full Text

References

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