Hereditary dysfibrinogenemia characterized by slow fibrinopeptide release and competitive inhibition of thrombin.
A qualitative abnormality of fibrinogen was identified in a 40-year-old woman with recurrent thrombophlebitis. Fibrinogen levels were normal when determined by immunologic, gravimetric, or nephelometric methods (200-390 mg/dl), but were diminished when tested by techniques based on the thrombin time (13 mg/dl). Asymptomatic family members, including both parents of the proposita, were less severely affected (mean fibrinogen level 100 mg/dl). The rate of fibrinopeptide release from purified fibrinogen was abnormally slow, whereas purified fibrin monomers polymerized at a normal rate. The abnormal fibrinogen was found to act as a competitive inhibitor of thrombin with an inhibitor constant (Ki) of 0.2 microM. This value was the same as the Michaelis constant (Km) of the normal thrombin-fibrinogen reaction, an observation consistent with an abnormality that retards fibrinopeptide release without affecting enzyme-substrate affinity.
D000328:Adult; D001778:Blood Coagulation Disorders / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D005344:Fibrinopeptide A / Q000378:metabolism; D006801:Humans; D007122:Immunoelectrophoresis; D007700:Kinetics; D010375:Pedigree
D005344:Fibrinopeptide A; D005340:Fibrinogen