Physiological Effects of the Plasma Kallikrein-Kinin System: Roles of the Blood Coagulation Factor XII (Hageman Factor)

Abstract

For many decades the intrinsic coagulation research has focused on factor XII (Hageman factor; FXII) and its significant role as a sole instigating factor driving the stabilization of thrombotic clotting. FXII is a relatively weak risk factor for thrombosis although its amidolytic and proteolytic function renders its presence important. Accumulating evidence suggests that FXII is pivotally involved in pathologic coagulation. In particular, the role of FXII in initiation and propagation of the blood coagulation and fibrinolytic systems has impeccable scientific support to the extent of which the existence of a "FXII-dependent pathway of thrombosis" is now generally accepted. The concept, although not a new one to scientists in the field of coagulation, is a caveat to the pathologic clot forming FXII concept in that it appears to cause a conceptual shift in de-emphasizing the inherent complexity of FXII activation representing a spectrum of responses. For instance, FXII contributes to the activation of inflammation and complement systems and influences catecholamine release from the adrenal system, suggesting that FXII can trigger multiple signaling pathways upon activation. The nature and duration of each of the FXII-dependent pathways may depend not only on the kind of stimulus, but also it may have distinct response pattern under normal and pathophysiologic conditions.Because a plethora of pathophysiological pathways are influenced by FXII, additional studies into its role as an important first step behind regulating common daily stresses may promise to provide new insight to better understand the unique and subtle biology behind FXII.