Fibrinogen St. Louis: A New Inherited Fibrinogen Variant, Coincidentally Associated with Hemophilia A

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

Section: Introductionmentioning

confidence: 99%

Fibrinogen Philadelphia. A hereditary hypodysfibrinogenemia characterized by fibrinogen hypercatabolism.

Martinez

Holburn²,

Shapiro³

et al. 1974

“…This delay has been demonstrated in fibrinogen Zurich (6), fibrinogen Detroit (5), fibrinogen Cleveland (8), fibrinogen St. Louis (50), and fibrinogen Los Angeles (57). Fibrinogen Paris II (9) and the fibrinogen reported by Verstraete (58) exhibited a slight delay in fibrin monomer aggregation.…”

Section: Discussionmentioning

confidence: 82%

“…Unlike fibrinogen Baltimore (7), its ultracentrifugal behavior was normal (Fig. 4) as was that of fibrinogen Detroit (5), fibrinogen St. Louis (50), and, apparently, fibrinogen Paris I (2). Chromatographic behavior of fibrinogen Bethesda on DEAE-cellulose was also normal (Fig.…”

Section: Discussionmentioning

confidence: 89%

“…Chromatographic behavior of fibrinogen Bethesda on DEAE-cellulose was also normal (Fig. 7), a respect in which it differed from fibrinogens Baltimore (7) and Paris I (51) but was similar to fibrinogen St. Louis (50) and fibrinogen Oklahoma (52,53 (56). Fibrinogen Bethesda presented a complex immunoelectrophoretic situation; the pattern given by plasma was consistently abnormal, whereas in purified fibrinogen preparations the difference from normal fibrinogen was not as great.…”

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

Fibrinogen Bethesda: a congenital dysfibrinogenemia with delayed fibrinopeptide release

Gralnick¹,

Givelber²,

Shainoff³

et al. 1971

112

A B S T R A C T A dysfibrinogenemia (fibrinogen Bethesda) was detected in a 9 yr old male of MexicanEnglish extraction who had a lifelong history of mild bleeding diathesis. The prothrombin and partial thromboplastin times were moderately prolonged; the thrombin and Reptilase times were markedly prolonged. The plasma fibrinogen level was normal by conventional methods but was markedly reduced by the Clauss method. Results of all other tests for clotting factors, fibrinolysis, antithrombin levels, clot stabilization, and fibrin(ogen) degradation products were normal. The patient's plasma and fibrinogen inhibited the clotting of normal plasma or fibrinogen by thrombin. Family studies revealed that the propositus' mother and two siblings exhibited these abnormalities to a lesser degree and indicated an autosomal dominant inheritance. Fibrinogen Bethesda was similar to normal fibrinogen in the following respects: metabolic turnover time (measured in the propositus' mother); immunodiffusion, ultracentrifugal, electrophoretic (on cellulose acetate or polyacrylamide gel), and chromatographic (on DEAE-cellulose) characteristics; sialic acid content; and aggregation of fibrin monomers. By contrast, fibrinogen Bethesda gave an abnormal immunoelectrophoretic pattern especially when whole plasma (as opposed to purified fibrinogen) was examined, and it showed a pronounced decrease in the rate of fibrinopeptide release by thrombin. This decrease, which was shown to involve both fibrinopeptides A and B, distinguishes fibrinogen Bethesda from previously reported dysfibrinogenemias. INTRODUCTIONCongenital abnormalities related to the function of fibrinogen have been reported in detail in eight families (1-9).

“…Total fibrinopeptide release was measured by a method adapted from that described by Sherman, Gaston, Kaplan, and Spivack (28), in which the guanidino group of arginine is measured fluorometrically after the addition of aqueous ninhydrin at alkaline pH (29). Arginine is COOH-terminal amino acid in both fibrinopeptides A and B; thus, its appearance in the supernatant fluid after clotting is a measure of release of the fibrinopeptides.…”

Section: Introductionmentioning

confidence: 99%

Fibrinogen Cleveland II AN ABNORMAL FIBRINOGEN WITH DEFECTIVE RELEASE OF FIBRINOPEPTIDE A

Crum¹,

Shainoff²,

Graham³

et al. 1974