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 μM. 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.

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