Histone H3 may be More Closely Associated with Disseminated Intravascular Coagulation and Multiple Organ Failure Than

Hiromitsu Kuroda1, Shingo Yamada2, Shintaro Suzuki1

  • 1Department of Intensive Care Medicine, School of Medicine, Sapporo Medical University, Sapporo, Hokkaido, Japan.

BackgroundAmong damage-associated molecular patterns (DAMPs), the specific contributions of histone and high mobility group box 1 (HMGB1) levels to disseminated intravascular coagulation (DIC) and multiple organ dysfunction (MOD) remain unclear. In this study, we aimed to investigate the association between two DAMP markers, plasma histone H3 and HMGB1 levels, and concurrent DIC and Sequential Organ Failure Assessment (SOFA) score in critically ill patients.MethodsPlasma levels of histone H3 and HMGB1 were prospectively quantified in 46 critically ill patients who demonstrated systemic inflammatory response syndrome, possible sepsis, and required intensive care unit (ICU) treatment. We analyzed two DAMP marker values, various plasma-inflammatory and non-inflammatory cytokine levels, acute DIC on ICU day 3, and the maximum SOFA score at 48 h after ICU admission.ResultsOn ICU day 3, 25 patients had DIC while 21 did not. In multivariate logistic regression analysis, plasma histone H3 levels (odds ratio [95% confidence interval]: 1.17 [1.02- 1.49], p = 0.008) and TNF-α (1.006 [1.001- 1.014], p = 0.007) were significant independent factors of DIC pathogenesis. The Spearman's rank correlation coefficients for the maximum SOFA score were 0.664, 0.602, 0.348, and 0.221 for IL-8, IL-6, histone H3, and HMGB1, respectively.ConclusionIn the early phase requiring intensive care, histone H3 levels exhibited a more positive association with the onset of DIC than HMGB1. Conversely, inflammatory cytokines may exert a more substantial influence on the pathogenesis of multiple organ failure in comparison to DAMPs.

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