The plasma contact system sits atop the intrinsic coagulation cascade and plasma kallikrein-kinin pathway, and in vivo its activation contributes, respectively, to coagulation and inflammation mainly via two downstream pathways. This system has been widely investigated, its activation mechanisms by negatively charged surfaces and the interactions within its components, factor XII, prekallikrein and high molecular weight kininogen are well understood at the biochemical level. However, as most of the activators that have been discovered by in vitro experiments are exogenous, the physiological activators and roles of the contact system have remained unclear and controversial. In the last two decades, several physiological activators have been identified, and a better understanding of its roles and its connection with other signaling pathways has been obtained from in vivo studies. In this article, we present an overview of the contact pathway with a focus on the activation mechanisms, natural stimuli, possible physiological roles, potential risks of its excessive activation, remaining questions and future prospects.
Keywords: Coagulation; Contact activation; Factor XII; Inflammation; Kallikrein–kinin.