Nonanticoagulant heparin prevents histone-mediated cytotoxicity in vitro and improves survival in sepsis

Karin C. A. A. Wildhagen, Pablo Garcia de Frutos, Chris P. Reutelingsperger, Roy Schrijver, Cristina Areste, Almudena Ortega-Gomez, Niko M. Deckers, H. Coenraad Hemker, Oliver Soehnlein, Gerry A. F. Nicolaes*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

163 Citations (Web of Science)

Abstract

Extracellular histones are considered to be major mediators of death in sepsis. Although sepsis is a condition that may benefit from low-dose heparin administration, medical doctors need to take into consideration the potential bleeding risk in sepsis patients who are already at increased risk of bleeding due to a consumption coagulopathy. Here, we show that mechanisms that are independent of the anticoagulant properties of heparin may contribute to the observed beneficial effects of heparin in the treatment of sepsis patients. We show that nonanticoagulant heparin, purified from clinical grade heparin, binds histones and prevents histone-mediated cytotoxicity in vitro and reduces mortality from sterile inflammation and sepsis in mouse models without increasing the risk of bleeding. Our results demonstrate that administration of nonanticoagulant heparin is a novel and promising approach that may be further developed to treat patients suffering from sepsis.
Original languageEnglish
Pages (from-to)1098-1101
JournalBlood
Volume123
Issue number7
DOIs
Publication statusPublished - 13 Feb 2014

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