Figure 2. Crosstalk between Kallikrein-Kinin System (KKS), coagulation, fibrinolysis and complement cascade.
Kallikrein-Kinin system (KKS) (black box and arrows) consists of tissue and plasma kallikrein which act on high molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK) to generate bradykinin (BK) and kallidin (Lys-BK). BK and Lys-BK, and their metabolites (Lys-des-Arg9-BK and DABK) act via two G-coupled receptors, B1R and B2R, resulting in increased vascular permeability, vasodilation, edema formation and ultimately hypotension. Plasma kallikrein, which is induced by the reciprocal activation of the Factor XIIa (FXIIa) and plasma prekallikrein, also influences the fibrinolytic pathway by activating plasminogen into plasmin and leading to fibrin degradation and D-dimer generation (yellow box and arrows). Beyond its role in KKS, FXIIa starts the intrinsic coagulation pathway (red arrows). Blood coagulation consists of an intrinsic and extrinsic (grey arrows) pathways, both resulting in activation of Factor X (FX), which subsequently leads to thrombin and fibrin generation (common pathway; blue arrows). The coagulation cascade is also a starting point for the complement system (pink box and arrows). FXIIa binds C1q component of the complement triggering the classic pathway; moreover, plasmin activation, which is also promoted via B2 signalling, triggers C3 cleavage inducing the activation of both lecithin and extrinsic pathways of the complement.