Thrombin generation and mortality during Staphylococcus aureus sepsis

Sepsis-induced abnormalities of coagulation may contribute to mortality during severe bacterial infection. The aim of this study was to examine changes in coagulation parameters and to assess the role of protein C supplementation during murine S. aureus sepsis. Gram-positive sepsis was characterized by a hypercoagulable state with predominant activation of the external coagulation pathway, registered as an early increase of tissue factor activity and concomitant reduction in protein C. The internal coagulation pathway was unaffected. No correlation between the changes of coagulation parameters and the intensity of inflammation, determined as serum IL-6 levels, was found. Supplementation with neither protein C or APC favoured survival in S. aureus sepsis. Reduction in thrombin generation in response to protein C supplementation was associated with significantly increased survival.