• Karin C A A Wildhagen, Pablo García de Frutos, Chris P Reutelingsperger, Roy Schrijver, Cristina Aresté, Almudena Ortega-Gómez, Niko M Deckers, H Coenraad Hemker, Oliver Soehnlein, and Gerry A F Nicolaes.
• Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands;
• Blood. 2014 Feb 13;123(7):1098-101.

AbstractExtracellular 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.

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