Bacterial infection and activation of the contact pathway of coagulation.

The excessive inflammatory and prothrombotic response to a bacterial infection creates a life-threatening medical condition in sepsis. The transition from localized to systemic thrombin generation is a hallmark of disseminated intravascular coagulation (DIC), a severe prothrombotic disorder resulting in microvascular thrombosis and subsequent multiorgan failure. The contact pathway of coagulation has been shown to play roles both in the initiation and amplification of thrombin generation in models of sepsis. The contact pathway consists of the coagulation factors XII (FXII) and XI (FXI), prekallikrein, and high- molecular-weight kininogen. Activation of the contact pathway can be triggered by binding to anionic surfaces, such as the ionized phosphoryl and carboxylate groups present on bacterial surface macromolecules. In particular, FXII has been shown to bind to the components of the bacterial envelope, including adhesins, peptidoglycan, lipopolysaccharides from gram-negative bacteria, and lipoteichoic acids from gram-positive bacteria. This review discusses the molecular pathways linking activation of the contact pathway by the envelope structures of bacterial and downstream thrombin generation and inflammation associated with sepsis-induced coagulopathies. We highlight the potential for FXII and FXI as potential therapeutic options for safely preventing DIC in sepsis.