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Colistin dampens fibrinolysis and endothelial activation during endotoxaemia. A randomised, double blind trial.

ABSTRACT: Colistin electrostatically interacts with lipopolysaccharides (LPS). Pre-clinical studies demonstrated beneficial effects of colistin on LPS-induced coagulation and fibrinolysis. The objective of this trial was to investigate the effects of colistin during experimental endotoxaemia. In this randomised, double-blind, placebo-controlled, crossover trial 16 healthy volunteers received a 2 ng/kg LPS bolus after infusion of 2.5 million IU colistin or placebo. Plasma levels of F1+2 prothrombin fragments, thrombin-antithrombin complexes (TAT), von Willebrand factor antigen levels (vWF), E-selectin, plasmin-antiplasmin complexes (PAP), tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor-1 (PAI-1) were measured. Infusion of colistin significantly reduced peak concentrations of PAP complexes by 70?%, t-PA antigen levels by 63?% and t-PA activity by 48?%, while PAI-1 levels decreased numerically by 63?%. Two hours after the LPS bolus F1+2 levels and TAT complexes were slightly reduced in the colistin period, but peak concentrations were similar in both periods. Colistin blunted the LPS induced four-fold increase in soluble E-Selectin levels by ~50?% and the two-fold increase in vWF antigen levels by ~70?%. The LPS-scavenging actions of colistin significantly reduce endothelial activation and fibrinolytic response in the human endotoxaemia model, while the activation of the coagulation system remains largely unaffected.

SUBMITTER: Schoergenhofer C

PROVIDER: S-EPMC6292133 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Colistin dampens fibrinolysis and endothelial activation during endotoxaemia. A randomised, double blind trial.

Schoergenhofer Christian C Matzneller Peter P Mußbacher Marion M Schmid Johannes A JA Jilma-Stohlawetz Petra P Zeitlinger Markus M Jilma Bernd B

Thrombosis and haemostasis 20170810 9

Colistin electrostatically interacts with lipopolysaccharides (LPS). Pre-clinical studies demonstrated beneficial effects of colistin on LPS-induced coagulation and fibrinolysis. The objective of this trial was to investigate the effects of colistin during experimental endotoxaemia. In this randomised, double-blind, placebo-controlled, crossover trial 16 healthy volunteers received a 2 ng/kg LPS bolus after infusion of 2.5 million IU colistin or placebo. Plasma levels of F1+2 prothrombin fragmen ...[more]

PMID: 28796276

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Colistin dampens fibrinolysis and endothelial activation during endotoxaemia. A randomised, double blind trial.

Publications

Colistin dampens fibrinolysis and endothelial activation during endotoxaemia. A randomised, double blind trial.

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