RSS-Feed abonnieren
DOI: 10.1055/s-0038-1647646
Fibrinogen Nijmegen : Congenital Dysfibrinogenemia Associated with Impaired t-PA Mediated Plasminogen Activation and Decreased Binding of t-PA
Publikationsverlauf
Received 17. März 1988
Accepted after revision 06. Mai 1988
Publikationsdatum:
24. Juli 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/198801/lookinside/thumbnails/10-1055s-0038-1647646-1.jpg)
Summary
Congenital dysfibrinogenemia was found in a patient with venous thrombosis. Blood clot lysis was prolonged and suggested an impairment of fibrinolysis. We investigated whether this was related to the fibrinogen abormality. Fibrinopeptide release was normal but fibrin polymerization was defective in the patient. The stimulating effect of the patient’s fibrin on t-PA mediated plasminogen activation was impaired. This could not be attributed to defective binding of plasminogen. However, the binding of t-PA to the patient’s fibrin was about 16% less than to normal fibrin. A variant t-PA (G K1 K2 P), which contained only one of the two fibrin binding sites, i.e. the kringle-2 domain, was bound to the abnormal fibrin for only 50% of normal.
We conclude that the prolongation of blood clot lysis and the impaired stimulation of t-PA mediated plasminogen activation are related to the defective binding of the kringle-2 domain of t-PA onto the fibrin moiety of the abnormal fibrinogen. The impairment of fibrinolysis might explain the occurrence of throm-bosis in the patient.
-
References
- 1 Rupp C, Beck EA. Congenital dysfibrinogenemia. In: Variants of Human Fibrinogen. Beck EA, Furlan M. (Eds) Huber; Bern: 1984: 65-130
- 2 Liu CY, Nossel HL, Kaplan KL. Defective thrombin binding by abnormal fibrin associated with recurrent thrombosis. Thromb Haemostas 1979; 42: 79 (Abstr)
- 3 Haverkate F, Koopman J, Kluft C, D’Angelo A, Cattaneo M, Mannucci PM. Fibrinogen Milano II: a congenital dysfibrinogenemia associated with juvenile arterial and venous thrombosis. Thromb Haemostas 1986; 55: 131-135
- 4 Liu CY, Nossel HL, Kaplan KL. The binding of thrombin by fibrin. J Biol Chem 1979; 254: 10421-10425
- 5 Carrell N, Gabriel DA, Blatt PM, Carr ME, McDonagh J. Hereditary dysfibrinogenemia in a patient with thrombotic disease. Blood 1983; 62: 439-447
- 6 Soria J, Soria C, Caen JP. A new type of congenital dysfibrinogenemia with defective fibrin lysis - Dusard syndrome: possible relation to thrombosis. Br J Haematol 1983; 53: 575-586
- 7 Lijnen HR, Soria J, Soria C, Collen D, Caen JP. Dysfibrinogenemia (fibrinogen Dusard) associated with impaired fibrin-enhanced plasminogen activation. Thromb Haemostas 1984; 51: 108-109
- 8 Bachmann F, Kruithof EK O. Tissue plasminogen activator: chemical and physiological aspects. Sem Thromb Hemostas 1984; 10: 6-17
- 9 Hoylaerts M, Rijken DC, Lijnen HR, Collen D. Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin J Biol Chem 1982; 257: 2912-2919
- 10 Rånby M, Wallén P. Enzymatic properties of tissue-type plasminogen activator. In: Thrombolysis: Biological and Therapeutic Properties of New Thrombolytic Agents. Collen D, Lijnen HR, Verstraete M. (Eds) Churchill-Livingstone; Edinburgh: 1985: 30-48
- 11 Nieuwenhuizen W, Vermond A, Voskuilen M, Traas DW, Verheijen JH. Identification of a site in fibrin(ogen) which is involved in the acceleration of plasminogen activation by tissue-type plasminogen activator. Biochim Biophys Acta 1983; 748: 86-92
- 12 Thorsen S, Clemmensen I, Sottrup-Jensen L, Magnusson S. Adsorption to fibrin of native fragments of known primary structure from human plasminogen. Biochim Biophys Acta 1981; 668: 337-387
- 13 Verheijen JH, Caspers MP M, Chang GT G, de Munk GA W, Pouwels PH, Enger-Valk BE. Involvement of finger domain and kringle 2 domain of tissue-type plasminogen activator in fibrin binding and stimulation of activity by fibrin. EMBO J 1986; 5: 3525-3530
- 14 Abildgaard U, Lie N, Odegaard OR. Antithrombin (heparin cofactor) assay with new chromogenic substrates. Thromb Res 1977; 11: 549-553
- 15 Bertina RM, Broekmans AW, Van der Linden IK, Mertens K. Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemostas 1982; 48: 1-5
- 16 Bertina RM, van Wijngaarden A, Reinalda-Poot J, Poort SR, Bom VJ J. Determination of plasma protein S - the protein cofactor of activated protein C. Thromb Haemostas 1985; 53: 268-272
- 17 Friberger P, Knös M, Gustavsson S. Methods for determination of plasmin, antiplasmin and plasminogen by means of substrate S-2251. Haemostasis 1978; 7: 138-145
- 18 Rijken DC, Van Hinsbergh VW M, Sens EH C. Quantitation of tissue-type plasminogen activator in human endothelial cell cultures by use of an enzyme immunoassay. Thromb Res 1984; 33: 145-153
- 19 Binnema DJ, Van Iersel JJ L, Dooijewaard G. Quantitation of urokinase antigen in plasma and culture media by use of an ELISA. Thromb Res 1986; 43: 569-577
- 20 Verheijen JH, Chang GT G, Kluft C. Evidence for the occurrence of a fast-acting inhibitor for tissue-type plasminogen activator in human plasma. Thromb Haemostas 1984; 51: 392-395
- 21 Mancini G, Carbonara AO, Heremans JE. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 1965; 2: 235-254
- 22 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 57-65
- 23 Van Ruijven-Vermeer IA M, Nieuwenhuizen W. Purification of rat fibrinogen and its constituent chains. Biochem. J 1978; 169: 653-658
- 24 Kluft C, Van Wezel AL, Van der VeldenC A M, Erneis JJ, Verheijen JH, Wijngaards F. Large-scale production of extrinsic (tissue-type) plasminogen activator from human melanoma cells. In: Advances in Biotechnological Processes 2. A. R. Liss Inc; New York: 1983: 97-110
- 25 Gaffney PJ, Curtis AD. A collaborative study of a proposed international standard for tissue-type plasminogen activator (t-PA). Thromb Haemostas 1985; 53: 134-136
- 26 Erickson LA, Bergum PW, Hubert EV, Theriault NY, Rehberg EF, Palermo DP, De Munk GA W, Verheijen JH, Marotti KR. Enhancement of inhibition of recombinant analogs of tissue plasminogen activator. Thromb Haemostas 1987; 58: 287 (Abstr)
- 27 Kehl M, Lottspeich F, Henschen A. Analysis of human fibrinopeptide by high performance liquid chromatography. Hoppe Seyler’s Z Physiol Chem 1981; 362: 1661-1664
- 28 Jansen JW C M, Haverkate F, Koopman J, Nieuwenhuis HK, Kluft C, Boschman Th AC. Influence of factor XIII a activity on human whole blood clot lysis in vitro. Thromb Haemostas 1987; 57: 171-175
- 29 Laemmli UK. Cleavage of structural proteins during the assembly of the level of bacteriophage T4. Nature 1970; 227: 680-685
- 30 Verheijen JH, Mullaart E, Chang GT G, Kluft C, Wijngaards G. A simple sensitive spectrophotometric assay for extrinsic (tissue-type) plasminogen activator applicable to measurements in plasma. Thromb Haemostas 1982; 48: 266-269
- 31 Helmkamp RW, Goodland RL, Bale WF, Spar IL, Mutchler LE. High specific activity iodination of gamma-globulin with iodine 131 I-mono-chloride. Cancer Res 1960; 20: 1495-1500
- 32 Koopman J, Haverkate F, Koppert P, Nieuwenhuizen W, Brommer EJ P, Van der Werf WG C. New enzyme immunoassay of fibrinfibrinogen degradation products in plasma using a monoclonal antibody. J Lab Clin Med 1987; 109: 75-84
- 33 Thorsen S. Differences in the binding to fibrin of native plasminogen and plasminogen modified by proteolytic degradation. Influence of w-amino-carboxylic acids Biochim Biophys Acta 1975; 393: 55-56
- 34 Brommer EJ P, Boks AL, Koopman J, Haverkate F. Protraction of whole blood and plasma clot lysis in patients with high levels of an inhibitor of tissue-type plasminogen activator. Thromb Res 1985; 39: 271-280
- 35 Liu CY, Wallén P, Handley DA. Fibrinogen New York 1: Mechanism for defective fibrin potentiation of plasminogen activation by tissue plasminogen activator. Thromb Haemostas 1985; 54: 108 (Abstr)