Untersuchungen an einer angeborenen Afibrinogen�mie

Gross, R; Schwick, G.; Lang, N.; Nies, Diethard; Rahn, Burkhard; Becker, Margarete; Hengstmann, H

doi:10.1007/bf01478415

Cited by 18 publications

(6 citation statements)

References 41 publications

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“…These enzymes may inhibit aggregation of platelets by thrombin by effects on constituents of the platelet surface other than fibrinogen. Platelets from some patients with congenital afibrinogenemia lacked fibrinogen by immunochemical techniques, but were aggregated by thrombin and agglutinated by antifibrinogen antibody (33). Such platelets may contain either trace amounts of normal fibrinogen or another protein, possibly related to fibrinogen, which reacts with thrombin in the production of platelet aggregation.…”

Section: Resultsmentioning

confidence: 99%

Role of Platelet Fibrinogen in the Reactions of Platelets to Thrombin*

Morse¹,

Jackson²,

Conley³

1965

J. Clin. Invest.

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Washed human blood platelets contain a clottable protein that is similar to, if not identical with, plasma fibrinogen (1-4). After incubation with trypsin under appropriate conditions, platelets remain morphologically intact but no longer contain clottable protein (5). Trypsinized platelets, unlike normal platelets, are not aggregated by fresh serum or by a solution of thrombin and calcium chloride. When resuspended in plateletfree plasma or in a buffered solution of fibrinogen containing glucose, trypsinized platelets produce retraction of clots formed by thrombin; during the formation of the clot and its subsequent retraction, trypsinized platelets aggregate and undergo the usual changes of viscous metamorphosis (5). These observations suggest that fibrinogen on the surface of platelets is involved in the reaction of platelets to thrombin. This reaction does not consist simply of the coagulation of fibrinogen with entrapment of platelets in the fibrin mesh. Under usual conditions divalent cations are required for thrombin-induced platelet aggregation but not for clotting of fibrinogen (5, 6). Electron photomicrographs of platelet aggregates show no striated fibrin strands between adherent

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Section: Resultsmentioning

confidence: 99%

Role of Platelet Fibrinogen in the Reactions of Platelets to Thrombin*

Morse¹,

Jackson²,

Conley³

1965

J. Clin. Invest.

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“…Afibrinogenemia therefore most likeley is a quantitative and not a qualitative disorder of fibrinogen production. An implication of this finding is that there must exist "afibrinogenemias" of different degrees of severity, a fact which becomes quite evident whenever the different published case-reports are compared (5,9,15,24) . Only in pronounced deficiencies are the bleeding times found prolonged and spontaneous bleedings of a relatively mild type may occur, as is the case in our patients.…”

Section: Discussionmentioning

confidence: 96%

Platelet Function in Congenital Afibrinogenemia

Gugler¹,

Ef²

1965

Thromb Haemost

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SummaryPlatelet functions have been studied in relation to hemostasis in two patients with congenital afibrinogenemia.Neither in the plasma nor in the aqueous platelet extracts of these patients was fibrinogen detectable by immunoelectrophoresis or with the aid of the Ouchterlony technique. ADP-induced platelet aggregation, adhesion to connective tissue particles, viscous metamorphosis under the influence of thrombin, clot retraction activity of the platelets, as well as their factor 3 activity were all found normal. Abnormal was the behaviour of the patient’s platelets on glass surfaces : they were unable to adhere to glass and the typical spreading on such surfaces was equally missing. This defect was normalized in vitro by the addition of small amounts of fibrinogen and correspondingly the patients platelets showed normal adhesiveness after fibrinogen transfusions. Normal platelets, suspended in afibrinogénémie plasma lost their adhesiveness toward glass surfaces.After transfusion of Cohn fraction I the prolonged bleeding time of the patients was normal and the clinical improvement presisted for a period of about 3 weeks, this inspite of the fact, that no fibrinogen was detectable by the usual methods 10 days after the transfusion.The significance of these results as well as their implications for the role of fibrinogen in hemostasis are discussed.

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“…It is interesting to note that one family with dysfibrinogenemia (8) was originally described as hypofibrinogenemia. Electrophoresis of the plasma proteins usually allows a differentiation between afibrinogenemia and dysfibrinogenemia, because in afibrinogenemia the fibrinogen is completely absent or the traces require a special immunoelectrophbretic technique (50). With turbidometric techniques or precipitation techniques one can always measure fibrinogen in plasma of patients with dysfibrinogenemia, but the amounts may be decreased (1,2,5,8).…”

Section: Discussionmentioning

confidence: 99%

Congenital dysfibrinogenemia: fibrinogen detroit

Mammen¹,

Prasad²,

Barnhart³

et al. 1969

J. Clin. Invest.

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A B S T R A C T A 17 yr old female with a congenital bleeding disorder was found to suffer from dysfibrinogenemia. Whole blood and plasma coagulation times were delayed and thrombelastograms were grossly abnormal. Clottability of plasma fibrinogen by addition of thrombin was not demonstrated during the 30 min test period. Fibrinogen was revealed by turbidometric and immunologic techniques. Other coagulation factors were present in normal amounts and prothrombin activation was normal. Patient's plasma inhibited thrombin clotting times of normal plasma and purified normal fibrinogen. Fibrinolysis was not detected.The plasma fibrinogen migrated normally on paper and cellulose acetate electrophoresis, but on immunoelectrophoresis it displayed a faster mobility than normal fibrinogen. On immunodiffusion the antigenic determinants were similar to those of normal fibrinogen. The patient's fibrinogen-antifibrinogen precipitins required longer to appear and the resultant precipitin was broader and hazier than those elicited with normal fibrinogen. These findings suggest the presence of two discrete populations of fibrinogen molecules.Investigation of the family of the patient suggested that the defect has an autosomal dominant pattern of heredity. Immunologic comparisons of our patient's plasma and of her relatives with plasma of patients with "Fibrinogen Baltimore" and "Fibrinogen Cleveland" revealed certain differences in immunoelectrophoretic mobility as well as in immunodiffusion. In keeping with the nomenclatures of abnormal fibrinogens in the literature, we propose the term "Fibrinogen Detroit" for this fibrinogen.Physicochemical properties of "Fibrinogen Detroit" were investigated also and compared with those of nor- In an investigation with Doctors Blomback a specific molecular defect was revealed in the N-terminal disulfide knot of the alpha (A) chain in which the arginine at the 19th position was replaced by serine. It is believed that the substitution of a strongly basic amino acid with a neutral hydroxy acid may result in considerable conformational changes in the N-terminal disulfide knot of fibrinogen which might affect the "active site" for polymerization. The lower carbohydrate content observed in "Fibrinogen Detroit" may have been the result of a change in primary and tertiary structure of the protein.

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Untersuchungen an einer angeborenen Afibrinogen�mie

Cited by 18 publications

References 41 publications

Role of Platelet Fibrinogen in the Reactions of Platelets to Thrombin*

Role of Platelet Fibrinogen in the Reactions of Platelets to Thrombin*

Platelet Function in Congenital Afibrinogenemia

Congenital dysfibrinogenemia: fibrinogen detroit

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