Self-generated cofactor-assisted substrate interactions of thrombin. Once thrombin has cleaved FPA from fibrinogen, fibrin monomer is formed, to which the thrombin remains attached via exosite I interactions at the N-terminal E domain (A). Factor XIII (FXIII) is also loosely bound to fibrin, but at the C-terminal D domain (B). The fibrin monomers will spontaneously polymerize. It has been proposed that this approximates the thrombin and factor XIII (C), resulting in efficient cleavage of the activation peptide (AP).⁴⁷  Fibrin(ogen) polypeptide chains are colored as in figure 3A.