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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:483.)
© 2004 American Heart Association, Inc.

Vascular Biology

Inhibition of Plasmin Activity by Tranexamic Acid Does Not Influence Inflammatory Pathways During Human Endotoxemia

Rosemarijn Renckens; Sebastiaan Weijer; Alex F. de Vos; Jennie M. Pater; Joost C. Meijers; C. Erik Hack; Marcel Levi; Tom van der Poll

From the Laboratory of Experimental Internal Medicine (R.R., S.W., A.F.d.V., J.M.P., T.v.d.P.), Departments of Vascular Medicine (J.C.M., M.L.) and Infectious Diseases (T.v.d.P.), Tropical Medicine & AIDS, Academic Medical Center, University of Amsterdam; and the Sanquin Research at the CLB (C.E.H.), Amsterdam, The Netherlands.

Correspondence to Rosemarijn Renckens, MD, Laboratory of Experimental Internal Medicine, Academic Medical Center, Room G2-132, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. E-mail r.renckens{at}amc.uva.nl

Objective— Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems.

Methods and Results— To determine the role of early plasmin activity in LPS-induced inflammation in vivo, 16 healthy males received an intravenous bolus injection with LPS (from Escherichia coli, 4 ng/kg) directly preceded by a 30-minute intravenous infusion of tranexamic acid (2 g, n=8), a plasmin activation inhibitor, or placebo (n=8). LPS injection induced marked increases in the plasma levels of D-dimer and plasmin-2-antiplasmin complexes, indicative of plasmin activation and generation, respectively, which were strongly attenuated by tranexamic acid (both P<0.01 versus placebo). However, tranexamic acid did not influence LPS-induced coagulation activation, granulocytosis, neutrophil activation (expression of CD11b, CD66b, and L-selectin) or degranulation (plasma concentrations of elastase-1-antitrypsin and bactericidal permeability-increasing protein), endothelial cell activation (plasma levels of von Willebrand factor and soluble E-selectin), or cytokine release.

Conclusion— These data argue against a role of early plasmin generation in the subsequent activation of other inflammatory pathways during human endotoxemia.

Key Words: fibrinolysis • coagulation • vascular biology

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