Fibrinogen Philadelphia. A hereditary hypodysfibrinogenemia characterized by fibrinogen hypercatabolism.

Abstract

A B STR A CT A new, autosomally inherited abnormal fibrinogen associated with hypofibrinogenemia has been described in several members of a family. Plasma fibrinogen measured either as thrombin-clottable protein or by immunodiffusion revealed a fibrinogen level ranging 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. Purified fibrinogen prolonged the thrombin time of normal plasma. Fibrinopeptide release by thrombin was normal in rate and amount, but fibrin monomer aggregation was grossly disturbed, especially in a high ionic strength medium. We have designated this fibrinogen "fibrinogen Philadelphia." Acrylamide gel electrophoresis of mixtures of ["'I]normal and ['I]abnormal fibrinogens revealed a slight increase in the anodal mobility of fibrinogen Philadelphia. Similarly, DEAEcellulose chromatography showed slightly stronger binding of fibrinogen Philadelphia than normal. To elucidate the mechanism responsible for the low plasma fibrinogen concentration, simultaneous metabolic studies of autologous (patient) and homologous (normal) fibrinogen, labeled with 1'I and 181I, respectively, were performed in two affected subjects. Autologous fibrinogen half-life was short and the fractional catabolic *rate was markedly increased in both family members. In contrast, homologous fibrinogen half-life and fractional catabolic rate were normal. These metabolic studies demonstrate that rapid degradation of fibrinogen This work wvas presented in part at the 64th Annual

Fibrinogen induces endothelial cell permeability

“…We found that Fg concentration was greater in spontaneously hypertensive rats (3.7 ± 0.3 mg/ ml) than in age-matched normotensive controls (2.4 ± 0.2 mg/ml) [9]. Fg is synthesized and assembled in hepatocytes and fibroblasts, and when secreted into the circulation, has a plasma half-life that ranges from 3 days to 4 days [12]. Synthesis of Fg involves other inflammatory mediators such as interleukin (IL)-6 and IL-1 [13,14], which like Fg, are associated with elevation of blood pressure [15][16][17] and development of hypertension [15,18,19], respectively.…”

Fibrinogen-independent platelet adhesion and thrombus formation on subendothelium mediated by glycoprotein IIb-IIIa complex at high shear rate.

“…Vitronectin was prepared and radiolabeled as described above. vWf, fibrinogen, and fibronectin were isolated as described previously (7,56,57 temperature for 2 h. These concentrations of adhesive proteins gave the maximal binding of platelets in dose-response isotherms. After incubation, the solutions were aspirated, and the wells were filled with TBS containing 1% (wt/vol) bovine serum albumin.…”

Fibrinogen Baltimore II: congenital hypodysfibrinogenemia with delayed release of fibrinopeptide B and decreased rate of fibrinogen synthesis.

“…However, the structure of the abnormal fibrin polymer may well be different from normal, as evidenced by the divergence in solution turbidity at later time points (Fig. 4) Congenital hypodysfibrinogenemia has been described in six families in addition to that reported here (44)(45)(46)(47)(48)(49). Fibrinogen Bethesda II (44), which manifests a slight delay in total fibrinopeptide release, also exhibits a major delay in fibrin monomer polymerization and is therefore dissimilar to fibrinogen Baltimore II.…”

“…Fibrinogen Bethesda II (44), which manifests a slight delay in total fibrinopeptide release, also exhibits a major delay in fibrin monomer polymerization and is therefore dissimilar to fibrinogen Baltimore II. The remaining proteins (45)(46)(47)(48)(49) are delayed only in the polymerization phase of coagulation. Thus, fibrinogen Baltimore II is readily distinguished from the other hypodysfibrinogens on the basis of its functional defect, a delay in fibrinopeptide B release.…”