Extracellular histone H3 levels are inversely correlated with antithrombin levels and platelet counts and are associated with mortality in sepsis patients

Abstract

Objective: Sepsis is a leading cause of death worldwide. Extracellular histones are cytotoxic compounds mediating death in murine sepsis and circulating nucleosome levels predict mortality in human inflammation and sepsis. Whether or not circulating extracellular histone H3 correlates with other plasma parameters and/or ICU scoring systems has not been completely established, nor if levels of circulating extracellular histones can be used as predictive markers for clinical outcome in sepsis.

Methods: We measured plasma histone H3 (H3) levels in the plasma of 43 sepsis patients who were admitted to the Intensive Care Unit and determined their correlation with disease severity, organ failure, mortality and coagulation- and tissue homeostasis parameters including LDH levels, thrombin potential (ETP), prothrombin levels, antithrombin levels and platelet counts.

Results: Median H3 levels of sepsis patients at the ICU were significantly increased in non-survivors as compared to survivors with levels found being 3.15μg/ml versus 0.57μg/ml respectively, P=0.04. H3 levels are positively correlated with lactate dehydrogenase (LDH) activity (Spearman's rho=0.49, P<0.001), and negatively correlated with antithrombin levels (rho=-0.34, P=0.027) and platelet counts (rho=-0.33, P=0.031).

Conclusions: We conclude that circulating H3 levels correlate with mortality in sepsis patients and inversely correlate with antithrombin levels and platelet counts.

Keywords: Antithrombin; Histones; Mortality; NETosis; Sepsis; Thrombin generation.