Thromb Haemost 1970; 24(01/02): 100-112
DOI: 10.1055/s-0038-1654215
Originalarbeiten – Original Articles – Travaux Originaux
Schattauer GmbH

The Influence of Inhibitors of Plasmin and Plasminogen Activation on the Streptokinase-Induced Fibrinolytic State

F Spöttl*
1   Department of Internal Medicine (Head: Prof. Dr. H. Braunsteiner) University of Innsbruck, Innsbruck, Austria
,
F Holzknecht
1   Department of Internal Medicine (Head: Prof. Dr. H. Braunsteiner) University of Innsbruck, Innsbruck, Austria
› Author Affiliations
Further Information

Publication History

Publication Date:
28 June 2018 (online)

Summary

The influence of the inhibitors of plasminogen activation by streptokinase, urokinase and tissue activator and of the two antiplasmins i.e. α1 antitrypsin and α2-macroglobulin, upon the formation and clearance of streptokinase-activator in vivo was investigated in 22 subjects. No influence of the above mentioned inhibitors on the formation of the streptokinase-activator could be found, whereas the clearance of the activator seems to be a function of the α2-macroglobulin level before streptokinase administration. The clearance rate of the streptokinase-activator differed significantly from the clearance rate of 131I labelled streptokinase caused by antigen-antibody complex formation [Fletcher et al. (10)], and was similar to the clearance rate of the histamine or nicotinic acid induced plasminogen activator. The possibility of a common clearing mechanism of fibrinolytic activators is discussed.

The existence of 3 different inhibitors activities on plasminogen activation as tested in vitro i. e. inhibitor of streptokinase, urokinase and tissue activator, was demonstrated. These inhibitory activities are probably not the properties of 3 different serum proteins but rather the result of the action of α1antitrypsin and α2-macroglobulin. The degree of inhibition, however, of each of the 2 proteins on each of the 3 plasminogen activators (streptokinase, urokinase and tissue activator) seems to be different. This difference may be caused by a different inhibitory effect of α1 antitrypsin or α2-macroglobulin on each of the plasminogen activators.

The plasmin formed after the streptokinase infusion is rapidly bound by the α2macroglobulin and this plasmin-antiplasmin complex is immediately removed from the blood, causing a decrease of the α2-macroglobulin level. This decrease of α2-macroglobulin is correlated with the initial level of α2-macroglobulin. This finding demonstrates the concentration depending formation of the plasmin-antiplasmin complex also in vivo.

* Authors address: Dr. F. Spöttl, Med. Univ. Klinik, Anichstraßé 35, A-6020 Innsbruck.


 
  • References

  • 1 Amery A, Vermylen J, Verstraete M. Changes in fibrinolytic parameters during and after prolonged streptokinase administration. Abstr. 12th Congr. int. Soc. Haemat. New York: 1968: 185.
  • 2 Alkjaersig N, Fletcher A. P, Sherry S. The mechanism of clot dissolution by plasmin. J. clin. Invest 38: 1086 1959;
  • 3 Astrup T, Müllertz S. The fibrin plate method for estimating fibrinolytic activity. Arch. Biochem 40: 346 1952;
  • 4 Bachmann F, Fletcher A. P, Alkjaersig N, Sherry S. Partial purification and properties of the plasminogen activator from pig heart. Biochemistry 03: 1578 1964;
  • 5 Bennett N. B. A method for the quantitative assay of inhibitor of plasminogen activation in human serum. Thrombos. Diathes. haemorrh. (Stuttg.) 17: 12 1967;
  • 6 Brahman P, Astrup T. Selective inhibition in human pregnancy blood of urokinase induced fibrinolysis. Scand. J. clin. Lab. Invest 15: 603 1963;
  • 7 Brahman P, Mohler jr E. B, Astrup T. A group of patients with impaired plasma fibrinolytic system and selective inhibition of tissue activator-induced fibrinolysis. Scand. J. Haemat 03: 389 1966;
  • 8 Ghahrabarti R, Fearnley G. R, Hoching E. D, Delitheos A, Glarhe G. M. Fibrinolytic activity related to age in survivors of myocardial infarction. Lancet I: 573 1966;
  • 9 Deutsch E, Marschner I. Antifibrinolysine. Folia haemat. (Basel.) 08: 74 1963;
  • 10 Fletcher A. P, Alkjaersig N, Sherry S. The clearance of heterologous protein from the circulation of normal and immunized man. J. clin. Invest 37: 1306 1958;
  • 11 Fletcher A. P, Biederman O, Moore D, Alkjaersig N, Sherry S. Abnormal plasminogenplasmin system activity (fibrinolysis) in patients with hepatic cirrhosis: its cause and consequences. J. clin. Invest 43: 681 1964;
  • 12 Fletcher A. P. Pathological fibrinolysis. Fed. Proc 25: 84 1966;
  • 13 Ganrot P. O. Determination of α2-macroglobulin as trypsin-protein esterase. Clin. chim. Acta 14: 493 1966;
  • 14 Ganrot P. O, Scherstén B. Serum α2-macroglobulin concentration and its variation with age and sex. Clin. chim. Acta 15: 113 1967;
  • 15 Holemans R, Gross R. Influence of blood platelets on fibrinolysis. Thrombos. Diathes. haemorrh. (Stuttgart.) 06: 196 1961;
  • 16 Holemans R, Mann L. S, Cope G. Fibrinolytic activity of renal venous and arterial blood. Amer. J. Sci 254: 330 1967;
  • 17 Holemans R, Johnston J. G, McDonnell D. Origin and stability of blood plasminogen activator. Proc. 10th Congr. europ. Soc. Haemat., Strasbourg 1965. S. Karger; Basel/New York: 1967. part II, 1253.
  • 18 Housley J. Alpha 2-macroglobulin levels in disease in man. J. clin. Path 21: 27 1968;
  • 19 Hume R. Fibrinolysis in cardiac infarction. Brit. Heart J 20: 15 1958;
  • 20 Jacobsson K. Studies on fibrinogen. Scand. J. clin. Lab. Invest.. 07. Suppl 14 1955
  • 21 Johnson A. J, McCarty W. R. Experimental thrombolysis in man. Proc. Conf. on thrombolytic agents. U.S.P.H.S; Chicago: 1960: 173.
  • 22 Johnson A. J, Newman J. The fibrinolytic system in health and disease. Seminars in Haematology 01: 1 1964;
  • 23 Laurell C. B. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Ann. biol. Chem 15: 45 1966;
  • 24 Mann R. D, Cotton S, Jackson D. Antiplasmin activity of electrophoretically separated human serum fractions. J. clin. Path 19: 185 1966;
  • 25 Niléhn J. E, Ganrot P. O. Plasmin, plasmin inhibitors and degradation products of fibrinogen in human serum during and after intravenous infusion of streptokinase. Scand. J. clin. Lab. Invest 20: 113 1967;
  • 26 Nilsson I. M, Krook H, Sternby N. H, Söderberg E, Söderström N. Severe thrombotic disease in a young man with bone marrow and skeletal changes and with a high content of an inhibitor in the fibrinolytic system. Acta med. scand 169: 323 1961;
  • 27 Nilsson I. M, Olow B. Fibrinolysis induced by streptokinase in man. Acta chir. scand 123: 247 1962;
  • 28 Nilsson I. M, Olow B. Determination of fibrinogen and fibrinogenolytic activity. Thrombos. Diathes. haemorrh. (Stuttg.) 08: 297 1962;
  • 29 Norman P. S. Studies on the plasmin system. II. Inhibition of plasmin by serum or plasma. J. exp. Med 108: 53 1958;
  • 30 Norman P. S, Hill B. M. Studies on the plasmin system. III. Physical properties of the two plasmin inhibitors in plasma. J. exp. Med 108: 639 1958;
  • 31 Ottolander G. H. J.den, Leijnse B, Cremer-Elfrink H.M.J. Plasmatic and thrombocytic anti-plasmins and anti-activators II. Thrombos. Diathes. haemorrh. (Stuttg.) 21: 26 1969;
  • 32 Ottolander G. H. J.den, Leijnse B, Cremer-Elfrink H. M. J. Plasmatic and platelet antiplasmins and anti-activators, III. Results in normal people, in patients and in those with venous thrombosis. Thrombos. Diathes. haemorrh. (Stuttg.) 21: 35 1969;
  • 33 Paraskevas M, Nilsson I. M, Martinsson G. A method for determining serum inhibitors of plasminogen activation. Scand. J. clin. Lab. Invest 14: 138 1962;
  • 34 Remmert L. M, Cohen P. P. Partial purification and properties of a proteolytic enzyme of human serum. J. biol. Chem 181: 431 1949;
  • 35 Sandberg H, Tsitouris G, Deleon jr A. C, Bellet S. Studies on inhibition to the plasminplasminogen fibrinolytic enzymes in patients with myocardial infarction. Amer. J. Cardiol 05: 666 1960;
  • 36 Schnitze H. E, Heimburger N, Heide K, Haupt H, Störiko K, Schwick H. G. Preparation and characterisation of α1-trypsin inhibitor and α2-plasmin inhibitor of human serum. Proc. 9th Congr. europ. Soc. Haemat. Lissabon 1963. S. Karger, Basel; 1964: 1315.
  • 37 Schwick H. G. Biochemie der Fibrinolyse. Thrombos. Diathes. haemorrh. (Stuttg.) Suppl. 22: 27 1967;
  • 38 Shulman N. R. Studies on the inhibition of proteolytic enzymes by serum. III. Physiological aspects of variations in proteolytic inhibition. The concurrence of changes in fibrinogen concentration with changes in trypsin inhibition. J. exp. Med 95: 605 1952;
  • 39 Spöttl F. Die Bestimmung des Proaktivators des fibrinolytischen Fermentsystems mit einer quantitativen kaseinolytischen Methode. Thrombos. Diathes. haemorrh. (Stuttg.) 18: 393 1967;
  • 40 Spöttl F, Constantini R. Die Bedeutung des Proaktivators im fibrinolytischen Fermentsystem. Thrombos. Diathes. haemorrh. (Stuttgart.) 18: 416 1967;
  • 41 Spöttl F, Holzknecht F, Braunsteiner H. Enhancement of the fibrinolytic activity by venous occlusion in patients with primary “carbohydrate-induzed” hypertriglyceridemia. Acta haemat. (Basel.) 41: 154 1969;
  • 42 Steinbuch M, Quentin M, Pejaudier L. Technique d’isolement et étude de α2 makroglobuline. In: Proteides of the biological fluids, Proc. 12th Colloquium. Elsevier Press Inc; Amsterdam, London, New York: 1965: 375.
  • 43 Steinbuch M, Blatrix G, Josso F. α2-macroglobulin as progressiv antithrombin. Nature (Lond.) 216: 500 1967;
  • 44 Tillet W. S, Edwards L. B, Garner R. L. Fibrinolytic activity of hemolytic streptococci. The development of resistance to fibrinolysis following acute hemolytic streptococcus infections. J. clin. Invest 13: 47 1934;
  • 45 Tsitouris G, Sandberg H, Deleon jr A. G, Lecks L, Bellet S. Studies on the plasmin-plasminogen system in thrombo-embolic diseases. Its modifications by thrombolytic therapy. Amer. J. Cardiol 05: 680 1960;
  • 46 Tsitouris G, Bellet S, Eilberg R, Feihberg L. Effects of major surgery on plasmin-plasminogen inhibitors. Arch, intern. Med 108: 208 1961;
  • 47 Tsitouris G, Stathopoulou R, Tsevrenis I. Serum inhibition of plasmin and plasminogen activation in thrombotic diseases. J. Atheroscler. Res 07: 425 1967;
  • 48 Tytgat G, Collen D, de Vreker R, Verstraete M. Investigations on the fibrinolytic system in liver cirrhosis. Acta haemat. (Basel.) 40: 265 1968;
  • 49 Voss D. β-Pyridyl-Carbinol und Fibrinolyse. Med. Welt 52 1963; 2700.
  • 50 Warren B. A. Fibrinolytic activity of vascular endothelium. Brit. med. Bull 20: 213 1964;