Intrinsic coagulation cascade

The intrinsic coagulation cascade, also known as the contact activation pathway, is a complex series of proteolytic reactions that contribute to blood clot formation (StatPearls, 2023). It is initiated when Factor XII (FXII) comes into contact with negatively charged surfaces or polyanions, leading to the sequential activation of Factor XI (FXI), Factor IX (FIX), and Factor VIII (FVIII) (PubMed, PMID: 31550301). This pathway eventually converges with the extrinsic pathway at the common pathway to generate thrombin and fibrin. While the extrinsic pathway is primary for physiological hemostasis, the intrinsic pathway is a significant contributor to pathological thrombosis (NIH, 2022). Consequently, specific factors within this cascade, particularly FXI and FXII, have emerged as promising therapeutic targets for anticoagulants that aim to prevent thrombosis with minimal impact on normal bleeding times (Journal of Thrombosis and Haemostasis, 2021).

Other names

Contact activation pathwayIntrinsic pathway of blood coagulationContact system

Inhibition of specific serine proteases within the cascade, such as Factor XI or Factor XII, to prevent the amplification of the coagulation signal and subsequent thrombin generation (PubMed, PMID: 33443586).