1. Nat. Rev. Nephrol. doi:10.1038/nrneph.2017.17
Figure 3 Activation of the contact system, kallikrein/kinin pathway and coagulation system
Figure 3 | Activation of the contact system, kallikrein/kinin pathway and coagulation system. In response to adsorption to a biomaterial surface, the zymogen factor XII (FXII) becomes autoactivated to form α-FXIIa, which cleaves plasma FXII to form β-FXIIa (not shown). β-FXIIa can initiate two different pathways: the kallikrein (KK)/kinin pathway by cleaving prekallikrein (PK) to generate bradykinin (BK) and the intrinsic pathway of coagulation by activating FXI. High molecular weight kininogen (HK) is a cofactor for both of these reactions. In the KK/kinin pathway, PK is activated to form KK, which cleaves and releases the potent vasoactive and proinflammatory nonapeptide BK from HK. KK also activates FXII to form β-FXIIa, forming a powerful amplification loop. In the intrinsic pathway of coagulation, activated FXI (FXIa) activates FIX to FIXa, which together with its cofactor FVIIIa forms an active complex at the surface of activated platelets. This complex mediates proteolytic activation of FX to FXa, which together with FVa, activates prothrombin to form thrombin. As well as catalysing the conversion of FVIII and FV into their active forms, thrombin activates FXI so amplifies its own formation. Thrombin cleaves plasma fibrinogen to form soluble fibrin, which is converted to insoluble fibrin by FXIIIa. Thrombin also activates platelets via proteinase-activated receptor (PAR)-1 and PAR-4, so amplifies thrombus formation. When exposed in an active form following vessel damage or activation of blood cells, tissue factor (TF) initiates the extrinsic pathway of coagulation by functioning as an acceptor molecule for FVIIa, which is ubiquitously present in plasma in low amounts. This binding enables FVIIa to activate FIX and FX, which initiate the common pathway of coagulation. Modified with permission from Wiley © Ekdahl, K. N. et al. Immunol. Rev. 274, 245–269 (2016).
Modified with permission from Wiley © Ekdahl, K. N. et al. Immunol. Rev. 274, 245–269 (2016).
Ekdahl, K. N. et al. (2017) Cardiovascular disease in haemodialysis: role of the intravascular innate immune system
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