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Complement system activation through the alternative pathway associates with disseminated intravascular coagulation
Tomohiro Abe1, Katsutoshi Saito2, Takehiko Nagano2
1Department of Emergency and Critical Care Medicine, University of Miyazaki Hospital, Miyazaki, Japan; Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Insights
Sepsis with complement activation worsens severity and causes thrombocytopenia. The combination of complement activation and disseminated intravascular coagulation (DIC) significantly increases sepsis mortality, with the alternative pathway being key.
Area of Science:
- Critical Care Medicine
- Immunology
- Hematology
Background:
- Sepsis-induced disseminated intravascular coagulation (DIC) is a major contributor to mortality in sepsis patients.
- Complement system activation frequently occurs alongside sepsis-induced DIC.
- The specific impact of these pathologies, individually and combined, on clinical sepsis parameters and mortality remains unclear.
Purpose of the Study:
- To investigate the influence of complement activation and DIC on clinical parameters in sepsis.
- To determine the association between complement pathway activation and sepsis-related mortality.
- To analyze the combined effects of complement activation and DIC on patient outcomes.
Main Methods:
- An ancillary analysis of a prospective observational study involving 49 adult sepsis patients.
- Patients were grouped based on the presence or absence of DIC and complement activation.
- Analysis of complement pathways (alternative, classical, lectin) and their correlation with clinical severity scores (APACHE2, SOFA) and 60-day mortality.
Main Results:
- Complement system activation was associated with induced thrombocytopenia and increased sepsis severity (APACHE2, SOFA scores).
- Sixty-day all-cause mortality was 0% in complement activation alone, 14% in DIC alone, and 66% in the combined DIC and complement activation groups.
- Higher levels of Bb, C3a/C3, and SC5b-9/C3 ratios were observed in non-survivors, particularly in the DIC+ subgroup.
Conclusions:
- Complement activation exacerbates sepsis severity and leads to thrombocytopenia.
- The co-occurrence of complement activation and DIC significantly elevates sepsis-related mortality.
- The alternative complement pathway plays a critical role in sepsis mortality.
Background:
Sepsis-induced disseminated intravascular coagulation (DIC) increases mortality in sepsis patients. Complement system activation is concomitant with sepsis-induced DIC; however, it is unclear how these two pathologies influence clinical parameters of sepsis individually and in combination, and which of the complement pathways activation is predominantly associated with mortality.
Methods:
In this ancillary analysis of a prospective observational study, 49 adult sepsis patients were assigned to four groups according to the absence/presence of DIC and complement activation. Effects of complement activation and DIC on clinical demographics including parameters of DIC, systemic severities, and 60-days all-cause mortality were assessed by comparing the groups. We analyzed each complement pathway by comparing Bb, C3a/C3 ratio, SC5b-9/C3 ratio, C4d, C4d/C4 ratio, C3a, C5a, and SC5b-9 between survivors/non-survivors both in all the patients and in the DIC+ subgroup.
Results:
Complement system activation induced thrombocytopenia and enhanced sepsis severity measured as APACHE2 and SOFA scores. 60-days all-cause mortality was different between groups, with 0 % in the complement activation alone group, 14 % in the DIC alone group and 66 % in the combined DIC and complement activation group. Bb and C3a/C3 and SC5b-9/C3 ratios were higher in non-survivors, with Bb and SC5b-9/C3 ratio still higher in DIC+ non-survivors.
Conclusion:
Complement activation worsen the severity of sepsis and cause thrombocytopenia. Co-occurrence of complement activation and DIC increased sepsis mortality. The alternative pathway of complement activation plays a major role in sepsis mortality.
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