Coagulation Factor XII (FXII) (FXII)

Coagulation Factor XII (FXII), also known as Hageman factor, is a 596-amino acid serine protease that circulates in the blood as an inactive zymogen. It is a key initiator of the intrinsic pathway of coagulation and the proinflammatory kallikrein-kinin system. Activation of FXII occurs upon contact with negatively charged surfaces, such as polyphosphates on platelets or artificial surfaces like medical devices, converting it into the active enzyme FXIIa (UniProt P00748). Unlike other coagulation factors, FXII is not essential for physiological hemostasis, as individuals with FXII deficiency do not exhibit abnormal bleeding (StatPearls: Physiology, Coagulation Cascade). This unique property makes FXII an attractive therapeutic target for preventing thrombosis without increasing bleeding risk. Additionally, FXIIa-mediated activation of prekallikrein leads to bradykinin release, making it a target for treating swelling disorders like hereditary angioedema. Current pharmacological approaches include monoclonal antibodies and antisense oligonucleotides that specifically inhibit FXIIa or reduce FXII expression (PMID: 32661328).

Other names

Hageman factorF12HAFCoagulation factor 12

Inhibition of activated Factor XII (FXIIa) protease activity or suppression of Factor XII synthesis to prevent intrinsic pathway activation and bradykinin formation.