A role of extracellular histones as mediators of death in sepsis

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We developed a sandwich ELISA to quantify serum or plasma histone H3 levels. The working range of this ELISA was 10-1000μg/L. Histone H3 was not detectable in plasma of healthy volunteers, but significant levels were observed in patients with sepsis and DIC. These levels were higher in non-survivors compared to survivors. Extracellular histones triggered platelet aggregation, leading to thrombotic occlusion of pulmonary capillaries and subsequent right-sided heart failure in mice. These mice displayed signs of DIC, including thrombocytopenia, prolonged prothrombin time, decreased fibrinogen, fibrin deposition in capillaries, and bleeding symptoms. These findings indicate that histones are released into the extracellular space during sepsis and act as a trigger for fatal thrombotic disorders.