Complement component consumption in sepsis correlates better with hemostatic system parameters than with inflammatory biomarkers

Introduction: The aim of this study was to investigate the role of C3 and C4 complement components in prediction of sepsis outcome. The secondary aim was to determine relationship between complement components and other inflammatory parameters, and parameters of hemostasis. Methods: One-hundred-thirty-seven patients with sepsis (Sepsis-3 criteria) were included in the study. Routine laboratory markers, predictive APACHEII and SOFA scores, concentrations of C3 and C4, activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin (AT), protein C (PC), protein S (PS), endogenous thrombin potential (ETP), thrombomodulin, and D-dimer were available. Concentrations of C3 and C4 were correlated with the disease outcome, predictive scores, inflammatory markers and parameters of hemostasis. Statistical analysis was performed using the non-parametric approach and significance was set at p < 0.05. Results: A significant depletion of the complement was observed in non-survivors (AUCROC(C3)= 0.692, p(C3) < 0.001, AUCROC(C4)= 0.672, p(C4)= 0.001). There was a significant negative correlation of C3and C4with APACHEII and SOFA (C3-APACHEII.=-0.364, p= 0.011, C3-SOFA.=-0.460, p < 0.001), aPTT (.=-0.407, p < 0.001), PT (.=-0.408, p < 0.001), and D-dimer (.=-0.274, p= 0.001). A significant positive correlation was observed with natural anticoagulants (C3-AT.= 0.493, p < 0.001; C3-PC.= 0.450, p < 0.001; C3-PS.= 0.345, p < 0.001), fibrinogen (rho= 0.481, p < 0.001), and ETP (rho= 0.384, p < 0.001). C3 and C4 correlated significantly only with CRP (rho= 0.207, p= 0.015), while no significant correlations with procalcitonin and WBC were detected. Results were similar for C4 and C3, although C3 presented higher correlation coefficients. Conclusion: In septic patients with poorer outcome, a significant depletion of the complement system was observed. Concentrations of complement components demonstrated stronger correlations with coagulation parameters than with inflammatory biomarkers.