Factor XI, also known as plasma thromboplastin antecedent, is a zymogen of factor XIa. It is involved in activation of the intrinsic coagulation pathway. Unlike factor XII, prekallikrein and high-molecular weight kininogen, deficiency of factor XI causes bleeding and factor XI has a physiological role in coagulation.
The gene for factor XI is located on chromosome 4 at 4q35. It is 23 kilobase long and has 14 introns and 15 exons.
Factor XI is disulphide linked dimer made of two homologous chains. Each chain is 80kDa and has 607 amino acids. 5% of the weight of factor IX is carbohydrate. The amino end has four 90-91 amino acid domains known as apple domains. These are homologous with similar domains found in prekallikrein. The carboxy end has a serine protease domains. Apple 1 domain mediates formation of complex with high-molecular weight kininogen, apple 2 domain mediated binding with factor IX, apple 3 domain binds factor IX, platelets and heparin and apple domain 4 has the dimerization site and is involved in association with factor XIIa.
Factor XI is activated by a cleavage of the Arg369-Ile370 bond. It is activated by factor XIIa, α-thrombin and factor XIa. Deficiency of factor XII does not cause bleeding but deficiency of factor XI does. The activation of factor XI by XIIa does not appear to have a physiological role. α-Thrombin is believed to the physiological activator of factor XI.
Factor XIa activates factor IX to IXa. Factor IXa is the enzymatic component of the factor X activating complex generated by intrinsic pathway. Factor XIa is a part of a positive feedback loop that activated prothrombin to thrombin via factors XI and X. The physiological role of factor XI seems to be to reinforce formation of thrombin.
Regulation of Factor XIa
Factor XIa is inhibited by plasma serpins. These include antithrombin, C1-inhibitor, protease nexin 1, and protein Z–related protease inhibitor, plasminogen activator inhibitor-1 and protein C inhibitor. Heparin enhances the inhibitory effects of srepins.