Upon activation, factor FXI is converted to factor XIa (FXIa) through a proteolytic cleavage at Arg387-Ile388 (Wu W et al., 2008; Emsley J et al., 2010; Mohammed BM et al., 2018). FXIa then activates factor IX to IXa, which subsequently activates factor X, promoting thrombin generation. Thrombin activates FXI creating a positive feedback loop that amplifies clot formation (Gailani D et al., 2014).
The protease activity of FXIa is regulated by plasma serpins, including C1-inhibitor (C1-INH) encoded by the SERPING1 gene (Meijers JC et al., 1988; Wuillemin WA et al., 1995, 1996a). SERPING1 binds to the light chain of FXIa, forming a non-reversible enzyme-inhibitor complex (Meijers JC et al., 1988). Heparin enhances serpin-mediated FXIa inhibition through interactions with heparin-binding sites on the apple 3 (A3) and catalytic domains of FXIa (Wuillemin WA et al., 1996b; Ho DH et al., 1998; Zhao M et al., 1998; Badellino KO & Walsh PN, 2001; Yang L et al., 2009).
