Fibrinogen Philadelphia. A hereditary hypodysfibrinogenemia characterized by fibrinogen hypercatabolism

fibrinogen associated with hypofibrinogenemia has been described in several members of a family. Plasma fibri-nogen measured either as thrombin-clottable protein or by immunodiffusion revealed a fibrinogen level rang-ing between 60 and 90 mg/100 ml. The thrombin time of plasma or purified fibrinogen was prolonged and only partially corrected by the addition of calcium. Puri-fied fibrinogen prolonged the thrombin time of normal plasma. Fibrinopeptide release by thrombin was nor-mal in rate and amount, but fibrin monomer aggrega-tion was grossly disturbed, especially in a high ionic strength medium. We have designated this fibrinogen "fibrinogen Philadelphia. " Acrylamide gel electro-phoresis of mixtures of ["'I]normal and ['I]abnormal fibrinogens revealed a slight increase in the anodal mobility of fibrinogen Philadelphia. Similarly, DEAE-cellulose chromatography showed slightly stronger bind-ing of fibrinogen Philadelphia than normal. To eluci-date the mechanism responsible for the low plasma fibrinogen concentration, simultaneous metabolic stud-ies of autologous (patient) and homologous (normal) fibrinogen, labeled with 1'I and 181I, respectively, were performed in two affected subjects. Autologous fibrin-ogen half-life was short and the fractional catabolic *rate was markedly increased in both family members. In contrast, homologous fibrinogen half-life and frac-tional catabolic rate were normal. These metabolic studies demonstrate that rapid degradation of fibrinoge