Contact system proteases (CAS) (CAS)

The contact system proteases, primarily comprising Coagulation Factor XII (FXII), Plasma Prekallikrein (PK), and Coagulation Factor XI (FXI), constitute a plasma protease cascade at the intersection of coagulation and inflammation [1, 3, 6]. This system is initiated by the auto-activation of FXII upon contact with negatively charged surfaces, leading to a reciprocal activation loop with PK and the subsequent activation of FXI [1, 15]. Biologically, these proteases drive the intrinsic pathway of blood coagulation and the kallikrein-kinin system, the latter of which releases the potent inflammatory mediator bradykinin [1, 4, 10]. Pathologically, dysregulation of this system is central to the development of hereditary angioedema (HAE) and contributes significantly to thrombotic disorders and systemic inflammatory responses such as sepsis [5, 7, 12]. Therapeutic targeting of these proteases, particularly FXIIa and plasma kallikrein, has emerged as a promising strategy for treating HAE and preventing thrombosis without the significant bleeding risks associated with traditional anticoagulants [6, 10, 13].

Other names

Contact activation system (CAS)Plasma kallikrein-kinin system (KKS)Intrinsic pathway of coagulationHageman factor system

Inhibition of serine protease activity to prevent the generation of bradykinin and thrombin.