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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

Dasja Pajkrt
1   Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
,
Peter G Lerch
2   ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland
,
Tom van der Poll
1   Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
,
Marcel Levi
3   Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Marlies Illi
2   ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland
,
Jan E Doran
2   ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland
,
Beat Arnet
2   ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland
,
Abraham van den Ende
3   Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Jan Wouter ten Cate
3   Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Sander J H van Deventer
1   Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 05 July 1996

Accepted after revision 22 October 1996

Publication Date:
10 July 2018 (online)

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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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