Factor XII

Factor XII (Hageman factor) is a glycoprotein synthesized by the liver that circulates in the blood as a zymogen. Factor XII is a coagulation factor in the intrinsic pathway of the coagulation cascade. The intrinsic pathway begins with the activation of factor XII (a zymogen, inactivated serine protease), which becomes factor XIIa(activated serine protease) after exposure to endothelial collagen. Endothelial collagen is only exposed when endothelial damage occurs. Factor XIIa acts as a catalyst to activate factor XI to XIa, which in turn activates factor IX to IXa. Factor IXa then catalyzes the conversion of factor X to Xa. 

The common pathway begins with the activation of factor X to factor Xa. Once activated, factor Xa converts factor II (prothrombin) to factor IIa (thrombin). In addition, factor Xa requires factor V as a cofactor to cleave prothrombin into thrombin. Factor IIa (thrombin) activates fibrinogen into fibrin. Thrombin also activates other factors in the intrinsic pathway (factor XI), cofactors V and VIII, and factor XIII. Fibrin subunits form fibrin strands, and factor XIII acts on fibrin strands to form a fibrin mesh. This mesh helps to stabilize the platelet plug.

Factor XII deficiency was first described in the medical literature in 1955 by doctors Oscar Ratnoff and Jane Colopy in a patient named John Hageman. It affects persons of Asian descent more often thatn other ethnicities. Males and females are affected equally. The incidence of factor XII deficiency in the general population is estimated to be approximately 1 in 1 million individuals. 

Hereditary deficiency of factor XII (Hageman factor) is usually diagnosed incidentally when a patient presents with an unexplained prolongation of the APTT, often during preoperative coagulation screening. There is general agreement that even severe factor XII deficiency is not associated with a clinical bleeding tendency. 

More controversial, however, is the role of factor XII deficiency as a possible prothrombotic risk factor. This is based on several case reports of venous thrombosis or myocardial infarction in patients with severe factor XII deficiency. Furthermore, several cohort studies of patients with venous or arterial thrombosis have suggested a higher than expected prevalence of factor XII deficiency, although case-control studies have failed to confirm this.

Reference

Demidova E et al, Factor XII deficiency: a clinical and molecular genetic study, Intl J Hematolog,2023;117:678-683.