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Complement component consumption in sepsis correlates better with hemostatic system parameters than with inflammatory
Dajana Lendak1, Dunja Mihajlovic2, Gorana Mitic3
1Department for Infectious Diseases, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia; Clinical Center of Vojvodina, Clinic for Infectious Diseases, Hajduk Veljkova 3, 21000 Novi Sad, Serbia.
Insights
Complement component depletion in sepsis patients predicts poorer outcomes. Lower levels of C3 and C4 correlated with disease severity and coagulation markers, suggesting their role in sepsis progression.
Area of Science:
- Immunology
- Critical Care Medicine
Background:
- Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
- The complement system, a crucial part of innate immunity, plays a role in host defense but can also contribute to tissue damage in sepsis.
Purpose of the Study:
- To investigate the predictive value of C3 and C4 complement components for sepsis outcomes.
- To determine the relationship between complement components and inflammatory markers, as well as hemostasis parameters in sepsis patients.
Main Methods:
- A cohort of 137 sepsis patients (Sepsis-3 criteria) was analyzed.
- Measurements included routine laboratory markers, APACHE II and SOFA scores, C3 and C4 concentrations, and various coagulation and inflammatory markers.
- Statistical analysis involved non-parametric methods to correlate complement levels with clinical outcomes and laboratory parameters.
Main Results:
- Significant depletion of C3 and C4 complement components was observed in non-survivors.
- Complement levels showed significant negative correlations with disease severity scores (APACHE II, SOFA) and procoagulant markers (aPTT, PT, D-dimer).
- Complement levels demonstrated significant positive correlations with natural anticoagulants (AT, PC, PS), fibrinogen, and endogenous thrombin potential (ETP), and a weaker correlation with CRP.
Conclusions:
- Complement system depletion is associated with poorer outcomes in sepsis patients.
- Complement component concentrations correlate more strongly with coagulation parameters than with inflammatory biomarkers in sepsis.
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 (AUCROCC3 = 0.692, pC3 < 0.001,AUCROCC4 = 0.672, pC4 = 0.001). There was a significant negative correlation of C3and C4with APACHEII and SOFA (C3-APACHEII ρ = -0.364, p = 0.011, C3-SOFA ρ = -0.460, p < 0.001), aPTT (ρ = -0.407, p < 0.001), PT (ρ = -0.408, p < 0.001), and D-dimer (ρ = -0.274, p = 0.001). A significant positive correlation was observed with natural anticoagulants (C3-AT ρ = 0.493, p < 0.001; C3-PC ρ = 0.450, p < 0.001; C3-PS ρ = 0.345, p < 0.001), fibrinogen (ρ = 0.481, p < 0.001),and ETP (ρ = 0.384, p < 0.001). C3 and C4 correlated significantly only with CRP (ρ = 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.
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