Factor xii deficiency D68.2

• Typical for factor XII deficiency is a lack of bleeding tendency. Therefore, the typical symptoms of coagulation disorders, e.g. nosebleeds, hematoma tendency, purpura, mucosal bleeding, gastrointestinal bleeding, increased bleeding in injuries and increased bleeding after trauma (e.g. intraoperative) are absent.
• Leading findings of factor XII deficiency are PTT prolongation with unremarkable Quick value and normal thrombin time.

• Based on the case of the first described patient with complete FXII deficiency, John Hageman, who died of a pulmonary embolism, FXII deficiency has long been considered a prothrombotic risk factor.

  Although individual other case reports are known in which people with deficient contact factors show increased thrombophilia, large clinical controlled trials in Switzerland and the Netherlands have clearly demonstrated that deficiency in FXII is not associated with an increased risk of thrombosis (Zeerleder et al. 1999).

  In 2009, Salomon et al. found evidence that deficiency of the FXIIa substrate FXI also protects humans from ischemic stroke (Salomon et al. 2009). Furthermore, a research group at the Institute of Clinical Chemistry and Laboratory Medicine at the University Medical Center Hamburg-Eppendorf was able to show that an absence or inhibition of other contact system factors such as plasma kallikrein and high-molecular-weight kininogen also protects against thrombosis without increasing the bleeding tendency (Nickel et al. 2017).

  Because of the potentially outstanding protective effect of "factor XII deficiency" against the occurrence of vascular occlusion due to thrombosis, the research group at the University Medical Center Hamburg-Eppendorf invites all FXII-deficient individuals to register at www.factor12.net (http://medistorage.net/f12/), where a registry of this rare congenital "coagulation anomaly" is being established. The research group would like to explore how the protective effect of a factor XII deficiency can also be used for people who have normal factor XII levels.

• Furthermore, acquired factor XII deficiency is also known to be caused by synthesis disorders or by turnover disorders (e.g. amyloidosis, nephrotic syndrome) or by inhibitors (e.g. in systemic lupus erythematosus or Smouldering Leucemia). In addition to its coagulatory function, factor XII starts the kallikrein-kinin system; this leads to the formation of the inflammatory mediator bradykinin.

• Factor XII is involved in the activation of the intrinsic and extrinsic coagulation cascade (activation of factors XI and VII) and fibrinolysis (cleavage of plasminogen) as well as in the activation of the complement system (activation of C1). The physiological inhibitor of factor XII is the C1 inhibitor. Coagulation factor XII is produced in the liver (molecular weight 80 kDa).

Notice! 2 very rarely occurring point mutations in the factor XII gene lead to type III hereditary angioedema (HAE-FXII).

1. Margolius A, Ratnoff OD (1956) Observations on the hereditary nature of Hageman trait. Blood 11: 565-569
2. Ratnoff OD, Margolius A (1955) Hageman trait: an asymptomatic disorder of blood coagulation. Trans Assoc Am Physicians 68: 149-154