Coagulation is controlled by a delicate balance of prothrombotic and antithrombotic mechanisms, to prevent both excessive blood loss from injured vessels and pathologic
thrombosis. The liver plays a pivotal role in hemostasis through the synthesis of plasma
coagulation factors and their inhibitors that, in addition to
thrombosis and hemostasis, orchestrates an array of inflammatory responses. As a result, impaired liver function has been linked with both
hypercoagulability and
bleeding disorders due to a pathologic balance of pro- and
anticoagulant plasma factors. At sites of
vascular injury,
thrombus propagation that finally may occlude the blood vessel depends on negatively charged
biopolymers, such as
polyphosphates and extracellular
DNA, that provide a physiological surface for contact activation of
coagulation factor XII (FXII). FXII initiates the contact system that drives both the intrinsic pathway of coagulation, and formation of the inflammatory mediator
bradykinin by the kallikrein-kinin system. Moreover, FXII facilitates receptor-mediated signalling, thereby promoting mitogenic activities, angiogenesis, and neutrophil stimulation with implications for
liver diseases. Here, we summarize current knowledge on the FXII-driven contact system in
liver diseases and review therapeutic approaches to target its activities during impaired liver function.