FXII

Factor XII (FXII), also called Hageman factor, is a clotting protein involved in the initiation of the intrinsic pathway of the coagulation cascade. It is a 222‑kDa glycoprotein produced by the liver and secreted into the bloodstream as a precursor. Upon contact with negatively charged surfaces, FXII becomes activated to its active form FXIIa, which then activates factor XI and triggers a cascade of enzymatic reactions leading to thrombin generation and fibrin clot formation.

The discovery of FXII dates back to 1933 when Dr. Karl Hageman observed a novel coagulation factor in patients with a rare bleeding disorder. Subsequent studies established that FXII deficiency in humans is associated with a prolonged activated partial thromboplastin time (aPTT) but does not cause a clinical bleeding tendency, indicating that FXII plays a more significant role in contact activation and in vivo pathways related to thrombosis rather than essential hemostasis.

FXII is encoded by the F12 gene located on chromosome 5q13.3. Genetic mutations in F12 lead to increased or decreased bleeding risks and have been linked to a hypercoagulable state known as thrombophilia. The protein participates in the kallikrein‑kinin system, potentially influencing blood pressure regulation and inflammatory responses.

Clinically, measurement of FXII activity may be used in the assessment of coagulation disorders, although routine testing is uncommon due to the protein’s lack of correlation with bleeding symptoms. Therapeutic strategies targeting FXII aim to reduce thrombotic risk without impairing normal hemostasis, making it a promising antithrombotic drug target.