PDF herunterladen
Thromb Haemost 1991; 66(06): 672-677
DOI: 10.1055/s-0038-1646484
Original Article
Schattauer GmbH Stuttgart

Influence of Intrinsic and Extrinsic Plasminogen upon the Lysis of Thrombi In Vitro

N Nishino
The Thrombosis Research Institute, Chelsea, London, United Kingdom
,
V V Kakkar
The Thrombosis Research Institute, Chelsea, London, United Kingdom
,
M F Scully
The Thrombosis Research Institute, Chelsea, London, United Kingdom
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 27. September 1990

Accepted 27. Mai 1991

Publikationsdatum:
26. Juli 2018 (online)

  als PDF herunterladen  Lizenzen und Reprints

Summary

When the rate of lysis of artificial thrombi (prepared from plasma or whole blood) was expressed according to the concentration of tissue type plasminogen activator (t-PA) or single chain urokinase type plasminogen activator (sc-uPA) then bell-shaped dose response curves were obtained, low rates being observed at concentrations of activator greater than 500 units/ml. Bell-shaped dose response curves were not observed for rate of lysis of artificial thrombi over the concentrations of streptokinase tested (SK) or for the lysis of plasma gel clots by any of the activators tested. Further investigation indicated that the preponderant mechanism for dissolution of thrombi at 500 units/ml of t-PA was by activation of the plasminogen within the thrombus (intrinsic) since the plasminogen present in the plasma perfusing the thrombus (extrinsic) rapidly became depleted. On the other hand, at 50 units/ml t-PA the lysis was observed to be due preponderantly to the action of plasmin arising from extrinsic rather than intrinsic plasminogen. If "plasminogen enriched" thrombi were prepared in the presence of Lys plasminogen (Lys-Plg) faster rates of lysis occurred and bell-shaped biometric curves were not observed.

 

  • References

  • 1 Collen D. On the regulation and control of fibrinolysis. Thromb Haemostas 1980; 43: 77-89
    PubMedGoogle Scholar
  • 2 Thorsen S. Differences in the binding to fibrin of native plasminogen and plasminogen modified by proteolytic degradation. Influence of ε-amino carboxylic acids. Biochim Biophys Acta 1985; 393: 55-65
    PubMedGoogle Scholar
  • 3 Camilio SM, Thorsen S, Astrup T. Fibrinogenolysis and fibrinolysis with tissue plasminogen activator, urokinase, streptokinase-activated human globulin, and plasmin. Proc Soc Exp Biol Med 1971; 139: 277-80
    PubMedGoogle Scholar
  • 4 Wallen P. Chemistry of plasminogen and plasminogen-activator. In: Progress in Chemical Fibrinolysis and Thrombolysis, Vol. 3.. Davidson JF, Rowan RM, Samama M, Desnoyers PC. (eds) Raven Press, New York: 1978. pp 167-81
    Google Scholar
  • 5 Takada A, Takada Y, Sugawara Y. Effect of fibrinogen and fibrin on the activation of Glu- and Lys-plasminogen by urokinase. Thromb Res 1984; 33: 561-9
    CrossrefPubMedGoogle Scholar
  • 6 Watahiki Y, Scully MF, Ellis V, Kakkar VV. Potentiation by Lys-plasminogen of clot lysis by single or two chain urokinase-type plasminogen activator or tissue-type plasminogen activator. Thromb Haemostas 1989; 61: 502-6
    PubMedGoogle Scholar
  • 7 Alkjaersig N, Fletcher AD, Sherry S. The mechanism of clot dissolution by plasmin. J Clin Invest 1959; 38: 1086-95
    CrossrefPubMedGoogle Scholar
  • 8 Nishino N, Scully MF, Rampling MW, Kakkar W. Properties of thrombolytic agents in vitro using a perfusion circuit attaining sheer stress at physiological levels. Thromb Haemostas 1990; 64: 550-5
    PubMedGoogle Scholar
  • 9 Poole JCF. A study of artificial thrombi produced by a modification of Chandlers method. Quart J Exp Physiol 1959; 44: 377-81
    PubMedGoogle Scholar
  • 10 Friberger P, Knos M. Plasminogen determination in human plasma. In: Chromogenic Peptide Substrates.. Scully MF, Kakkar VV. (eds) Churchill Livingstone, Edinburgh: 1979. pp 128-40
    Google Scholar
  • 11 Rakoczi I, Wiman B, Collen D. On the biological significance of the specific interaction between fibrin, plasminogen and antiplasmin. Biochim Biophys Acta 1978; 54: 295-300
    PubMedGoogle Scholar
  • 12 Sabovic M, Lijnen HR, Keber D, Collen D. Effect of retraction on the lysis of human clots with fibrin specific and non-fibrin specific plasminogen activators. Thromb Haemostas 1989; 62: 1083-7
    PubMedGoogle Scholar
  • 13 Scully MF, Strachan CJL, Kakkar VV. Binding of iodinated proteins to forming and preformed thrombi. Biochem Soc Trans 1973; 1: 1204-6
    CrossrefPubMedGoogle Scholar
  • 14 Strachan CJL, Scully MF, Kakkar W. The behaviour of isotopically labelled proteins in thrombosis. Thromb Res 1974; 4: 303-18
    CrossrefPubMedGoogle Scholar
  • 15 Wiman B, Wallen P. The specific interaction between plasminogen and fibrin. Thromb Res 1977; 10: 213-22
    CrossrefPubMedGoogle Scholar
  • 16 Lucas MA, Fretto LJ, McKee PA. The binding of human plasminogen to fibrin and fibrinogen. J Biol Chem 1983; 258: 4249-56
    PubMedGoogle Scholar
  • 17 Suenson E, Lutzen O, Thorsen S. Initial plasmin degradation of fibrin on the basis of the positive feedback mechanism in fibrinolysis. Eur J Biochem 1984; 140: 513-22
    CrossrefPubMedGoogle Scholar
  • 18 Sabovic M, Lijnen HR, Keber D, Collen D. Correlation between progressive adsorption of plasminogen to blood clots and their sensitivity to lysis. Thromb Haemostas 1990; 64: 450-4
    PubMedGoogle Scholar
  • 19 Ogston CM, Ogston D, Fullerton HW. Observations on the lysis of artificial thrombi by urokinase. Thromb Diath Haemorrh 1968; 19: 107-16
    PubMedGoogle Scholar
  • 20 Hedner U, Nilsson IM, Robertson B. Determination of plasminogen in clots and thrombi. Thromb Diath Haemorrh 1966; 16: 38-50
    PubMedGoogle Scholar
  • 21 Gottlob R, Stockinger L, Pötting U, Schattenman G. Studies on thrombolysis with streptokinase. Thromb Diath Haemorrh 1971; 25: 354-78
    PubMedGoogle Scholar
  • 22 Anderle K, Fröhlich A. Review of studies with plasminogen concentrates and proposals for further therapeutic strategies with plasminogen concentrates. Haemostasis 1988; S uppl. 18 165-75
    PubMedGoogle Scholar
  • 23 Westlund LE, Andersson L-O. Studies on the influence of reactants and buffer environment on clot lysis induced by human plasminogen activators. Thromb Res 1985; 37: 213-23
    CrossrefPubMedGoogle Scholar
  • 24 Collen D. Identification and some properties of the new fast acting plasmin inhibitor in human plasma. Eur J Biochem 1976; 69: 209-16
    CrossrefPubMedGoogle Scholar
  • 25 Mullertz S. Different molecular forms of plasminogen and plasmin produced by urokinase in human plasma and their relation to protease inhibitors and lysis of fibrinogen and fibrin. Biochem J 1974; 143: 273-83
    CrossrefPubMedGoogle Scholar
  • 26 Rånby M. Studies on the kinetics of plasminogen activation by tissue plasminogen activator. Biochem Biophys Acta 1982; 704: 461-9
    CrossrefPubMedGoogle Scholar
  • 27 Hoylaerts M, Rijken DC, Collen D. Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. J Biol Chem 1982; 257: 2912-9
    PubMedGoogle Scholar
  • 28 Aoki N, Moroi M, Matsuda M, Tachiya K. The behaviour of α2-plasmin inhibitor in fibrinolytic states. J Clin Invest 1977; 60: 361-9
    CrossrefPubMedGoogle Scholar
  • 29 Ichinose A, Tamaki T, Aoki N. Factor XIII mediated crosslinking of the NH2 terminal peptide of α2-plasmin inhibitor to fibrin. FEBS Lett 1982; 153: 369-71
    PubMedGoogle Scholar
  • 30 Tran-Thang C, Bachmann F. Binding of Lys-plasminogen, Lys-plasmin, streptokinase and of streptokinase plasminogen complex, to whole blood clots. Prog Fibr 1981; V: 363-3637
    PubMedGoogle Scholar
  • 31 Ljungberg J, Hedner U. Potentiated thrombolysis in a Chandler system using rtPA and Lys-plasminogen. Thromb Res 1989; 53: 569-76
    CrossrefPubMedGoogle Scholar
  • 32 Kakkar VV, Scully MF. Intermittent plasminogen-streptokinase treatment of deep vein thrombosis. Haemostasis 1988; 18: 123-8
    PubMedGoogle Scholar