Sepsis is a major cause of morbidity and mortality in dogs and is associated with thrombosis due to propensity for clot formation and reduced clot breakdown, termed hypofibrinolysis. Formation of neutrophil extracellular traps (NETs) consisting of extracellular DNA decorated with bactericidal proteins is an important host defense response. However, in excess this can lead to pathologic immunothrombosis. Formation of NETs also impairs fibrinolysis, and this predicts organ dysfunction and mortality in humans with sepsis. Fibrinolysis is inhibited by two key proteins, TAFI and PAI-1. We have observed increased TAFI activity in dogs with sepsis, but the role of PAI-1 in dogs with sepsis has not been described to date. Similarly, we have observed increased NET biomarker concentrations in dogs with sepsis, but do not know if these are associated with hypofibrinolysis.

This study will test three specific hypotheses:
1. Dogs with bacterial sepsis are hypofibrinolytic compared to dogs with non-septic critical illness
2. Activity of PAI-1 is increased dogs with sepsis and hypofibrinolysis
3. Increased NET biomarkers correlate with hypofibrinolysis in dogs with sepsis

We will enroll 26 dogs with sepsis and 26 dogs with non-septic critical illness as controls. We will measure plasma concentrations of three NET biomarkers and assess fibrinolysis using an overall hemostasis potential assay and through measurements of TAFI and PAI-1 activities. Fibrinolytic potential and NET biomarker concentrations will be compared between groups and the association between fibrinolysis and NETs assessed.