Download PDF
Thromb Haemost 1984; 51(03): 403-405
DOI: 10.1055/s-0038-1661112
Original Article
Schattauer GmbH Stuttgart

In Vitro Effects of the Acylated StreptokinasePlasminogen Activator Complex BRL 33 575 Incubated with Normal Human Plasma

B Lämmle
The Coagulation and Fibrinolysis Laboratory, Kantonsspital, Basel, Switzerland
,
G Noll
The Coagulation and Fibrinolysis Laboratory, Kantonsspital, Basel, Switzerland
,
T H Tran
The Coagulation and Fibrinolysis Laboratory, Kantonsspital, Basel, Switzerland
,
A Lohri
The Coagulation and Fibrinolysis Laboratory, Kantonsspital, Basel, Switzerland
,
F Duckert
The Coagulation and Fibrinolysis Laboratory, Kantonsspital, Basel, Switzerland
› Author Affiliations
Further Information

Publication History

Received 12 March 1984

Accepted 16 April 1984

Publication Date:
26 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Thrombolysis with acylated streptokinase-plasminogen complexes is aimed to achieve fibrinolysis without systemic fibrinogenolysis. The p-aminobenzoyl-streptokinase-(Lys)-plasminogen-complex (BRL 33 575) should be particularly useful due to its slow deacylation rate. Unexpectedly, repeated doses of 10 mg of BRL 33 575 (corresponding to 310'000 streptokinase equivalent units) induced systemic effects in patients though less than streptokinase alone. In vitro incubation of normal human plasma with BRL 33 575 at concentrations used in patients resulted in nearly complete consumption of α2-antiplasmin and plasminogen and significant fibrinogenolysis within 3 hr. This demonstrates that - despite of slow deacylation of BRL 33 575 - the small amounts of activator generated are highly efficacious in activating plasma plasminogen under conditions in which no physiological clearance of the free activator takes place. Simulating the calculated activator release from BRL 33 575 by infusing equivalent amounts of streptokinase into plasma resulted in less pronounced effects. This is probably explained by anti-streptokinase antibodies which will neutralize the initially infused streptokinase but will be bound by BRL 33 575.

Our in vitro experiments indicate that further clinical studies should be done with lower doses of BRL 33 575 or prolonged dosage intervals.

Keywords

Thrombolysis - Acylated streptokinase-plasminogen complex - α2-antiplasmin - Plasminogen - Fibrinogen
 

  • References

  • 1 Smith RA G, Dupe RJ, English PD, Green J. Fibrinolysis with acyl-enzymes: a new approach to thrombolytic therapy. Nature 1981; 290: 505-508
    CrossrefPubMedGoogle Scholar
  • 2 Smith RA G. Acyl-enzymes as fibrinolytic prodrugs. In: Progress in Fibrinolysis. Vol.VI. Davidson JF, Bachmann F, Bouvier CA, Kruithof EK O. (Eds.) Churchill Livingstone; Edinburgh, London, Melbourne, New York: 1983
    Google Scholar
  • 3 Smith RA G, Dupe RJ, English PD, Green J. Acyl-enzymes as thrombolytic agents in a rabbit model of venous thrombosis. Thromb Haemostas 1982; 47: 269-274
    PubMedGoogle Scholar
  • 4 Dupe RJ, English PD, Smith RA G, Green J. The activity of an acylated streptokinase plasminogen complex (BRL 26’921) in dog models of thrombosis. In: Progress in Fibrinolysis. Vol. VI. Davidson JF, Bachmann F, Bouvier CA, Kruithof EK O. (Eds.) Churchill Livingstone; Edinburgh, London, Melbourne, New York: 1983
    Google Scholar
  • 5 Lämmle B, Duckert F, Noll G, Lohri A, Marbet GA, Huber P, Biland L, Schmitt HE. Thrombolyse mit acylierten Streptokinase-Plasminogen-Komplexen (BRL 26’921 und BRL 33’575). 3. Kongreß für Thrombose und Blutstillung. Bern: 02/1984. (in press)
    Google Scholar
  • 6 Prowse CV, Hornsey V, Ruckley CV, Boulton FE. A comparison of acylated streptokinase-plasminogen complex and streptokinase in healthy volunteers. Thromb Haemostas 1982; 47: 132-135
    PubMedGoogle Scholar
  • 7 Fenech A, McGregor S, Davidson JF, Walker ID, Hutton I, Lawrie TD V. Single dose acyl-streptokinase-plasminogen activator complex in deep vein thrombosis. In: Progress in Fibrinolysis. Vol. VI. Davidson JF, Bachmann F, Bouvier CA, Kruithof EK O. (Eds.) Churchill Livingstone; Edinburgh, London, Melbourne, New York: 1983
    Google Scholar
  • 8 Fischbacher W. Beitrag zur fibrinolytischen Therapie mit Streptokinase und Fibrinolysin. Thrombos Diathes Haemorrh 1961; 6: 547-572
    PubMedGoogle Scholar
  • 9 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol (Basel) 1957; 17: 237-246
    CrossrefPubMedGoogle Scholar
  • 10 Noll G, Lämmle B, Duckert F. Plasmin inhibitors and fibrinogen breakdown during the initial phase of thrombolytic treatment. The problem of the α2-antiplasmin determination Thromb Haemostas 1984; 51: 334-337
    PubMedGoogle Scholar
  • 11 Friberger P, Knös M, Gustavsson S, Aurell L, Claeson G. Methods for determination of plasmin, antiplasmin and plasminogen by means of substrate S-2251. Haemostasis 1978; 7: 138-145
    PubMedGoogle Scholar
  • 12 Kabi Diagnostica. S-2251. Determination of plasminogen in plasma. Laboratory instruction
    PubMedGoogle Scholar
  • 13 Teger-Nilsson AC, Friberger P, Gyzander E. Determination of a rapid plasmin inhibitor in human blood by means of a specific tripeptide substrate. Scand J Clin Lab Invest 1977; 37: 403-409
    CrossrefPubMedGoogle Scholar
  • 14 Kabi Diagnostica. S-2251. Determination of antiplasmin in plasma with S-2251. Laboratory instruction
    PubMedGoogle Scholar