Hemostasis is a complex process that leads to the formation of a blood clot at the site of vessel injury. Three phases can be distinguished: primary hemostasis or formation of a platelet plug, secondary hemostasis, or coagulation and fibrinolysis (Kriz N et al. 2009). Defects in hemostasis cause an imbalance between the coagulation and fibrinolytic systems and may lead either to hypercoagulation, which can result in thrombosis, or to hypocoagulation and increased susceptibility to bleeding (also known as hemorrhagic diathesis) (van Herrewegen F et al. 2012a,b; Kumar R & Carcao M 2013). Abnormalities can result from disorders of the platelets (primary hemostasis defect), coagulation factors defects (secondary hemostasis defect), or a combination of both (van Herrewegen F et al. 2012a,b; Kumar R & Carcao M 2013). Coagulation disorders may be inherited or acquired. Further, abnormalities of the coagulation and fibrinolytic systems are coupled to the inflammatory response, which aggravates blood vessel permeability, inflammation, and cell damage in tissues (Sandra Margetic 2012; Kaplan AP & Joseph K 2016).
This Reactome module describes abnormalities of the coagulation cascade (secondary hemostasis) due to defects of coagulation factor proteins such as factor VIII (FVIII), FIX or FXII. The module also describes an abnormal FXII- mediated activation of the pro-inflammatory kallikrein‐kinin system (KKS) that leads to an excessive formation of bradykinin causing increased vascular permeability at the level of the post capillary venule and results in hereditary angioedema (HAE).