Fibrinogen Seattle: A Heritable Disfibrinogen with an Isolated Impairment in Fibrinopeptide B Release

The slow clotting, asymptomatic, fibrinogen Seattle first described in a patient with tetralogy of Fallot has been traced through four generations as an autosomal dominant with 70% penetrance. The dysfibrinogen was indistinguishable from normal fibrinogen by radial immunodiffusion and Immunoelectrophoresis. Transamidation and plasmin digestion studies gave no evidence of abnormality. Thrombin and botroxobin monomer reprolymerization followed turbidometrically (A₃₅₀) disclosed a shorter lag phase, a more acute maximal slope, and a lower maximal turbidity. Electron microscopy revealed that thrombin incubated fibrinogen Seattle more readily formed clots with aperiodic fibers than comparable controls. By amino acid analysis the final yield of fibrinopeptide B was slightly more than half normal (54% at 2 hours with 2.5 NIH units/ml). The dysfibrin manifested evidence of retent ion of f ibrinopept ide B as equal quantities of chains with Bβ and β charge mobility were demonstrated on low pH (2.7) Polyacrylamide electrophoresis in 2M urea. A distinction is made between fibrinogen Seattle and fibrinogen Detroit both with disordered fibrinopeptide B release on the basis of the patterns of fibrinopeptide release, immunoelectrophoretic mobility, botroxobin monomer aggregation, Chronometric fibrinogen concentration, and clinical symptomatology. No other dysfibrinogens have been shown to manifest disordered release of fibrinopeptide B alone.