Factor XII


Synonym Hageman Factor
Molecular mass 80 000 Da
Synthesis Liver
Half life 40 - 50 hours
Plasma concentration 15 - 47 mg/l
Normal range 50 - 150% or 0.5 - 1.5 U/ml

Factor XIIa is the central enzyme of the contact activation phase of the intrinsic coagulation system. Binding of the proenzyme factor XII to negatively charged surfaces results in its activation to factor XIIa, which in turn activates prekallikrein to kallikrein. In a positive recoupling mechanism, kallikrein again activates factor XII. The coagulatory effect of factor XIIa is the activation of factor XI. In addition to the procoagulant effect of factor XIIa, the formation of kallikrein simultaneously results in both an activation of the fibrinolytic system and the kallikrein-kinin system.

Clinical significance

Hereditary factor XII deficiency is very rare. Acquired deficiencies may occur in connection with liver disease, increased consumption during DIC, lupus anticoagulants, nephrotic syndrome and rejection reactions. Increased factor XII concentrations are observed during pregnancy and in women taking oral contraceptives.


  • Suspected inherited factor XII deficiency
  • Suspected factor XII inhibitors
  • Differential diagnosis in patients with Lupus anticoagulants
  • Suspected disorders of the kallikrein-kinin system


  1. Fuhrer G et al. Factor XII. Blut 61, 255-266, 1990.
  2. Schousboe I et al. Functional Determination of Factor XII in Plasma. Clin Appl Thromb Haemost 2, 123-129, 1996.
  3. Walshe K et al. Microtiter chromogenic substrate assay for factor XII. Thromb Res 47, 365-371, 1987.
  4. Gallimore MJ et al. Factor XII determinations in the presence and absence of phospholipid antibodies. Thromb Haemost 79, 87-90, 1998.
  5. Tankersley D et al. Activation of Factor XII by Dextrane Sulfate: The Basis for an Assay of Factor XII. Blood 62, 448-456, 1983.
  6. Schmaier A et al. Activation of the Plasma Kallikrein/Kinin System on cells: A revised Hypothesis. Thromb Haemost 82, 226-233, 1999.
  7. Miller GJ et al. Risk of coronary heart disease and activation of factor XII in middle-aged men. Arterioscler Thromb Vasc Biol 17, 2103-6, 1997.
  8. Ozgu-Erdinc AS, Togrul C, Aktulay A, Buyukkagnici U, Yapar Eyi EG, Erkaya S. Factor XII (Hageman) levels in women with re-current pregnancy loss. J Pregnancy.2014, 459192, 2014.
  9. Matafonov A, Leung PY, Gailani AE, Grach SL, Puy C, Cheng Q, Sun MF, McCarty OJ, Tucker EI, Kataoka H, Renné T, Morrissey JH, Gruber A, Gailani D. Factor XII inhibition reduces thrombus formation in a primate thrombosis model. Blood. Mar 13, 123(11), 1739-46, 2014.
Test kits
Chromogenic Assays


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UNITEST Factor XIIa-like Activity

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UNITEST ?Factor XIIa Inhibitors

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UNITEST ?Factor XIIa Inhibitors

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Matched-Pair Antibody set


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