Factor XI

Factor XI or plasma thromboplastin antecedent is the is_associated_with::zymogen form of factor XIa, one of the is_associated_with::enzymes of the coagulation cascade. Like many other coagulation factors, it is a is_associated_with::serine protease. In humans, Factor XI is encoded by the F11 is_associated_with::gene.

Function
Factor XI (FXI) is produced by the is_associated_with::liver and circulates as a homo-dimer in its inactive form. The plasma half-life of FXI is approximately 52 hours. The zymogen factor is activated into factor XIa by is_associated_with::factor XIIa (FXIIa), is_associated_with::thrombin, and FXIa itself; due to its activation by FXIIa, FXI is a member of the "contact pathway" (which includes HMWK, is_associated_with::prekallikrein, is_associated_with::factor XII, factor XI, and is_associated_with::factor IX).

Factor XIa activates factor IX by selectively cleaving arg-ala and arg-val is_associated_with::peptide bonds. Factor IXa, in turn, activates is_associated_with::factor X.

Inhibitors of factor XIa include is_associated_with::protein Z-dependent protease inhibitor (ZPI, a member of the is_associated_with::serine protease inhibitor/serpin class of proteins), which is independent of is_associated_with::protein Z (its action on factor X, however, is protein Z-dependent, hence its name).

Structure
Although synthesized as a single polypeptide chain, FXI circulates as a homodimer. Every chain has a relative molecular mass of approximately 80000. Typical plasma concentrations of FXI are 5 μg/mL, corresponding to a plasma concentration (of FXI dimers) of approximately 30 nM. The FXI gene is 23kb in length, has 15 exons, and is found on chromosome 4q32-35.

Role in disease
Deficiency of factor XI causes the rare is_associated_with::hemophilia C; this mainly occurs in is_associated_with::Ashkenazi is_associated_with::Jews and is believed to affect approximately 8% of that population. Less commonly, hemophilia C can be found in Jews of Iraqi ancestry and in Israeli Arabs. The condition has been described in other populations at around 1% of cases. It is an is_associated_with::autosomal recessive disorder. There is little spontaneous bleeding, but surgical procedures may cause excessive blood loss, and prophylaxis is required.

Low levels of factor XI also occur in many other disease states, including is_associated_with::Noonan syndrome.

High levels of factor XI have been implicated in is_associated_with::thrombosis, although it is uncertain what determines these levels and how serious the procoagulant state is.