Factor XI Quick Facts
- Molecular mass: 160 000 D
- Synthesis: Liver
- Half-life: 60 – 80 hours
- Plasma concentration: 2 – 7mg/l
- Normal range: 70 – 130% Biochemistry of Factor XI
Factor XI (plasma thromboplastin antecedent) is the zymogen form of factor XIa, one of the enzymes of the coagulation cascade. It is a serine protease. During the contact activation phase of the intrinsic coagulation system factor XI is bound to negatively charged surfaces together with high molecular weight kininogen (HMWK). factor XIIa activates bound factor XI. In the next step factor XIa activates factor IX. In plasma, factor XI is bound to HMWK. Factor XI is also known as Rosenthal-Factor.
Zymogen factor XI is activated into factor XIa by factor XIIa (FXIIa), thrombin, and FXIa itself; due to its activation by FXIIa, FXI is a member of the “contact pathway” (which includes HMWK, prekallikrein, factor XII, factor XI, and factor IX).
Factor XIa activates factor IX by selectively cleaving arg-ala and arg-val peptide bonds. Factor IXa, in turn, activates factor X.
Factor XIa Inhibitors
Inhibitors of factor XIa include protein Z-dependent protease inhibitor (ZPI).
Factor XI Deficiency
Deficiency of factor XI is an autosomal recessive disorder that causes hemophilia C.
Low levels of factor XI also occur in many other disease states, including Noonan syndrome.
High levels of factor XI have been implicated in thrombosis, although it is uncertain what determines these levels and how serious the procoagulant state is.
Clinical significance of Factor XI
Cases of inherited factor XI deficiency have been observed. However, the bleeding tendency in these subjects is low. Liver disease, consumption coagulopathy and DIC lead to an acquired factor XI deficiency. In cases of autoimmune diseases, e.g. Lupus erythematosus, inhibitors against factor XI may be observed. Inhibitors may also be observed after substitution therapy. Recent findings suggest a correlation between increased levels of FIX and VTE. The increased thrombotic tendency may be due to an enhanced down regulation of fibrinolysis by activated TAFI (thrombin activatable fibrinolysis inhibitor).
Clinical or Research use of Factor XI
- Suspected inherited factor XI deficiency
- Suspected factor XI inhibitors
- Differential diagnosis in subjects with Lupus anticoagulants
- Suspected disorders of the kallikrein-kinin system
- Diagnosis of thrombophilia