The Ultrastructure of Fibrin Prepared from Fibrinogen Haifa (γ275 Arg→His)

Fibrinogen is composed of six polypeptide chains, 2 Aα, 2 Bβ and 2 γ chains, covalently linked at their amino termini by disulfide bonds. Fibrinogen is activated to α,β-fibrin by thrombin which cleaves 2 A (FPA) and 2B (FPB) fibrinopeptides from the N-termini. Release of FPA and FPB exposes'A'and'B' polymerization sites, respectively. The resulting fibrin self-associates into a branched 3-dimensional matrix. Two other types of fibrin can be formed in vitro: ct-fibrin [FPA release]and β-fibrin [FPB reelease). Fibrinogen Haifa is a congenital abnormal fibrinogen variant characterized by normal fibrinopeptide release, abnormal fibrin polymerization and replacement of γ275 Arg by His. The propositus has experienced thrombotic episodes. In this study the ultrastructure of fibrin formed from fibrinogen Haifa was compared to that of normal fibrin in order to better define the effect of the γ275 Arg → His substitution on its molecular function.