Sequential release of fibrinopeptides by thrombin action on fibrinogen is essential to normal fibrin polymerization. Cleavage of fibrinopeptide B from fibrinogen Bβ chains exposes E domain polymerization sites, E(B), that interact with platelets, fibroblasts, and endothelial cells.
Fibrin polymerization is initiated by thrombin cleavage of fibrinopeptide A from fibrinogen α chains, exposing two E domain E(A) sites. The phenylalanine at α chain residue 8 is important for efficient thrombin-catalyzed proteolysis of fibrinogen. Substitution of tyrosine for phenylalanine blocks sequential fibrinopeptide release and, thus, blocks polymerization and clot formation.