Immunohaemostasis: a new view on haemostasis during sepsis

Host infection by a micro-organism triggers systemic inflammation, innate immunity and complement pathways, but also haemostasis activation. The role of thrombin and fibrin generation in host defence is now recognised, and thrombin has become a partner for survival, while it was seen only as one of the "principal suspects" of multiple organ failure and death during septic shock. This review is first focused on pathophysiology. The role of contact activation system, polyphosphates and neutrophil extracellular traps has emerged, offering new potential therapeutic targets. Interestingly, newly recognised host defence peptides (HDPs), derived from thrombin and other "coagulation" factors, are potent inhibitors of bacterial growth. Inhibition of thrombin generation could promote bacterial growth, while HDPs could become novel therapeutic agents against pathogens when resistance to conventional therapies grows. In a second part, we focused on sepsis-induced coagulopathy diagnostic challenge and stratification from "adaptive" haemostasis to "noxious" disseminated intravascular coagulation (DIC) either thrombotic or haemorrhagic. Besides usual coagulation tests, we discussed cellular haemostasis assessment including neutrophil, platelet and endothelial cell activation. Then, we examined therapeutic opportunities to prevent or to reduce "excess" thrombin generation, while preserving "adaptive" haemostasis. The fail of international randomised trials involving anticoagulants during septic shock may modify the hypothesis considering the end of haemostasis as a target to improve survival. On the one hand, patients at low risk of mortality may not be treated to preserve "immunothrombosis" as a defence when, on the other hand, patients at high risk with patent excess thrombin and fibrin generation could benefit from available (antithrombin, soluble thrombomodulin) or ongoing (FXI and FXII inhibitors) therapies. We propose to better assess coagulation response during infection by an improved knowledge of pathophysiology and systematic testing including determination of DIC scores. This is one of the clues to allocate the right treatment for the right patient at the right moment.