Differential Effects of Reconstituted High-density Lipoprotein on Coagulation, Fibrinolysis and Platelet Activation during Human Endotoxemia

Dasja Pajkrt; Peter G Lerch; Tom van der Poll; Marcel Levi; Marlies Illi; Jan E Doran; Beat Arnet; Abraham van den Ende; Jan Wouter ten Cate; Sander J H van Deventer

doi:10.1055/s-0038-1655958

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1997; 77(02): 303-307
DOI: 10.1055/s-0038-1655958

Original Article

Schattauer GmbH Stuttgart

Differential Effects of Reconstituted High-density Lipoprotein on Coagulation, Fibrinolysis and Platelet Activation during Human Endotoxemia

Authors

Dasja Pajkrt

¹Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
Peter G Lerch

²ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland
Tom van der Poll

¹Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
Marcel Levi

³Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Marlies Illi

²ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland
Jan E Doran

²ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland
Beat Arnet

²ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland
Abraham van den Ende

³Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Jan Wouter ten Cate

³Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Sander J H van Deventer

¹Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands

Abstract

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Summary

High-density lipoproteins (HDL) can bind and neutralize lipopoly- saccharides (LPS) in vitro and in vivo. HDL can also affect fibrinolytic activity and can directly influence platelet function by reducing platelet aggregation. In this study, the effects of reconstituted HDL (rHDL) on LPS-induced coagulation, fibrinolysis and platelet activation in humans were investigated. In a double-blind, randomized, placebo-controlled, cross-over study, eight healthy male volunteers were injected with LPS (4 ng/kg) on two occasions, once in conjunction with rHDL (40 mg/kg, given as a 4 h infusion starting 3.5 h prior to LPS injection), and once in conjunction with placebo. rHDL significantly reduced LPS-induced activation of coagulation (plasma levels of prothrombin fragment F1+2) and fibrinolysis (plasma levels of tissue type plasminogen activator antigen, t-PA). No effect was observed on LPS-induced inhibition of the fibrinolytic pathway (PAI-1) or on the transient thrombocytopenia elicited by LPS. Furthermore, rHDL treatment significantly enhanced the inhibition of collagen-stimulated inhibition of platelet aggregation during endotoxemia, but had no such effect on arachido- nate-stimulated platelet aggregation. rHDL treatment per se also reduced collagen-induced platelet aggregation. These results indicate that rHDL modifies the procoagulant state associated with endotoxemia.

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References

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