Fibrinogen is an abundant plasma protein (5-10uM) produced in the liver. The intact protein has a molecular weight of 340kD and is composed of 3 pairs of disulfide-bound polypeptide chains named Aalpha, Bbeta and gamma. Fibrinogen is a triglobular protein consisting of a central E domain and terminal D domains. Proteolysis by thrombin results in release of Fibrinopeptide A (FPA, Aa1-16) followed by Fibrinopeptide B (FPB, Bb1-14) and the fibrin monomers that result polymerize in a half-overlap fashion to form insoluble fibrin fibrils. The chains of fibrin are referred to as a, b and g, due to the removal of FPA and FPB. The polymerized fibrin is subsequently stabilized by the transglutaminase activated Factor XIII that forms amide linkages between g chains and, to a lesser extent, a chains of the fibrin molecules. Proteolysis of fibrinogen by plasmin initially liberates C-terminal residues from the Aa chain to produce fragment X (intact DE- D, which is still clottable). Fragment X is further degraded to nonclottable fragments Y (D-E) and D. Fragment Y can be digested into its constituent D and E fragments. Digestion of non-crosslinked fibrin with plasmin is very similar to the digestion of fibrinogen, which results in production of fragments D and E. Degradation of crosslinked fibrin by plasmin results in fragment DD (D-Dimer consisting of the D domains of 2 fibrin molecules crosslinked via the y chains), fragment E (central E domain) as well as DDE in which fragment E is non-covalently associated with DD. For human crosslinked fibrin, the relative weights of the cleavage fragments produced are: 184kD for fragment DD, 92kD for D, 50kD for E, 1.54kD for FPA and 1.57kD for FPB.