Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). Chemically, this reaction involves the cleavage of a single peptide bond in each subunit of the factor XI homodimer; intra- and inter-chain disulfide bonds hold the resulting four polypeptides together (Bouma BN and Griffin JH 1977; Kurachi K and Davie EW 1977; McMullen BA et al. 1991). In the body, this reaction occurs on the surfaces of activated platelets, where factor IX (FIX) binds to the glycoprotein GPIb:IX:V receptor complex (Greengard JS et al. 1986; Baird TR and Walsh PN 2002; Baglia FA et al., 2004; Reitsma SE et al. 2021). When this reaction occurs as a step in the contact activation pathway, it is catalyzed by activated factor XIIa (Kurachi K and Davie EW 1977; Cheng Q et al., 2010), which is generated either through proteolytic cleavage by plasma kallikrein formed on endothelial cell surfaces (Schmaier AH, 2004; Shariat-Madar Z et al., 2002, 2004) or via FXII autoactivation upon binding of FXII to polyanionic surfaces, including platelet-released polyphosphates (Müller F et al., 2009; Engel R et al., 2014).
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