Model of fibrin polymerization

Thrombin (factor IIa) binds to fibrinogen and cleaves fibrinopeptide A and B (FPA and FPB) to generate fibrin monomers consisting of one E domain (open circle) and two D domains (closed circles). Adjacent monomers self-assemble to form protofibrils through interaction of complementary sites between the D and E domains (D-E contact). FPB release exposes additional determinants complementary with binding sites on the D domain, resulting in lateral growth and thickening of the protofibrils. Factor XIIIa induces formation of covalent bonds between adjacent D domains (D-D contact, shown as double lines) to stabilize the fibrin polymer. The exact spatial orientation of D-D cross-linking remains unresolved. There is evidence supporting both longitudinal as well as transverse cross-linking between adjacent D domains.