Complement system activation through the alternative pathway associates with disseminated intravascular coagulation to increase mortality in sepsis

Abstract

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.