Fibrinogen Seattle II: defective release of fibrinopeptide A in a slow clotting fibrinogen.

A functionally abnormal fibrinogen was detected in a 27-year-old woman with no prior history of bleeding. Investigation of the defect revealed abnormal release of fibrinopeptide A and incomplete polymerization of fibrin monomers. Crosslinking of polymerized fibrin by Factor XIII was normal. To further characterize the dysfibrinogen, the increase in mechanical impedance during clot development was measured. Fibrinogen Seattle II showed several differences from normal fibrinogen: delayed onset of clotting, decreased rate of clot formation, and lower final clot impedance. Taken cumulatively, these data are consistent with an amino acid substitution at or near residue 16 in one of the A alpha chains, the point at which thrombin cleaves.