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 and Griffin 1977; Kurachi and Davie 1977; McMullen et al. 1991). In the body, this reaction occurs on the surfaces of activated platelets (Greengard et al. 1986; Baglia et al. 2002; Baird and Walsh 2002); when this reaction occurs as a step in the intrinsic ("contact") pathway of blood coagulation, it is catalyzed by activated factor XIIa (Kurachi and Davie 1977, Baglia and Walsh 2000) which in turn is generated through the interactions of factor XII, kallikrein, and kininogen on endothelial cell surfaces (Schmaier 2004).