Thromb Haemost 1966; 16(03/04): 668-686
DOI: 10.1055/s-0038-1655653
Originalarbeiten — Original Articles — Travaux Originaux
Schattauer GmbH

Comparative Studies of Fibrinolytic Inhibitors in Vitro[*]

M Maki M. D., Ph. D1
1   From the Department of Obstetrics and Gynecology, New York University School of Medicine
,
F. K Beller M. D.2
1   From the Department of Obstetrics and Gynecology, New York University School of Medicine
› Author Affiliations
Further Information

Publication History

Publication Date:
24 July 2018 (online)

Summary

EACA, AMCHA, Trasylol and Soya bean trypsin inhibitor were compared in regard to their inhibition potency as enzyme and activator inhibitors in vitro, in different test systems. The ratio in all systems for Trasylol and STI was 1:4/6 depending on the test system used. Both substances are only slightly less active as activator inhibitors than as plasmin inhibitors. The difference however, is so small that Trasylol as well as STI can be regarded as good activator inhibitors in vitro. Both substances inhibit plasmin as well as activator competitively and differ therefore with EACA and AMCHA.

EACA and AMCHA are activator inhibitors and considerably less inactive in regard to plasmin inhibition. The already known fact that EACA inhibits the activator competitively was confirmed for AMCHA. The latter substance is 6-8 times more potent, than EACA.

EACA, AMCHA, Trasylol and STI given in combination resulted in an additive or synergistic action, rather than a potentiating one as has been described in vivo.

* This investigation was supported by a grant from the National Institute of Child Health and Human Development (HD 00270-05).


1 WHO Senior Research Trainee M8/181/4.


2 Career Scientist, Health Research Council of the City of New York under contract I-297.


 
  • References

  • 1 Alkjaersig N, Fletcher A. P, Sherry S. E-Aminocaproic Acid.: An Inhibitor of Plasminogen Activation. J. biol. Chem 234: 832 1959;
  • 2 Beck E, Schmutzler R, Duckert F. Inhibition of fibrinolysis and fibrinogenolysis in man: Comparison of E – amino-caproic-acid and Kallekrein inhibitor. Thrombos. Diathes. hemorrh. (Stuttg.) 10: 106 1963;
  • 3 Shimizu M, Naito T, Okano A, Aoyagi T. trans-4-Aminomethylcyclohexane carboxylic Acid as a Potent Antiplasmin Agent. Chem. pharm. Bull 13: 1012 1965;
  • 4 Remmert L. R, Cohen P. P. Partial purification and properties of a proteolytic enzyme of human serum. J. biol. Chem 181: 431 1949;
  • 5 Alkjaersig N, Fletcher A. P, Sherry S. The Activation of Human Plasminogen. II. (A kinetic study of activation E Trypsin, Urokinase, Streptokinase). J. biol. Chem 233: 81 1958;
  • 6 Lineweaver H, Burk D. The determination of enzyme dissociation constants. Amer. Chem. Soc 56: 658 1964;
  • 7 Marx R, Clemente P, Werle E, Appel W. Zum Problem eines Antidots in der internen Thrombotherapie mit Fibrinolytica. Blut 5: 367 1959;
  • 8 Johnson A. J, Skozal L, Clauss I. Observations on epsilon amino caproic acid. Thrombos. Diathes. haemorrh. (Stuttg.) 7: 111 1962;
  • 9 Nilsson J. M, Sjoersdma A, Waldenstroem J. Antifibrinolytic activity and metabolism of E-amino-caproic acid in man. Lancet I: 1322 1960;
  • 10 Okamoto A, Sato A, Takada Y, Okamoto U. An Active Stero-Isomer (Trans-Form) of AMCHA and its Antifibrinolytic (Antiplasminic) Action in vitro and in vivo. Keio J. Med 13: 177 1964;
  • 11 Kaller H. Tierexperimentelle Untersuchungen über Wirkungsdauer und Elemination von Trasylol. Arch, exper. Pathol. Pharmacol 246: 91 1963;
  • 12 Steichele D. F. Zur Antifibrinolytischen Wirkung des Trypsin-Kallikrein Inhibitors. Med. Welt (Stuttg.) 1961:2170
  • 13 Markwardt F, Kloecking H. P, Richter M. Die Kombinationswirkung von Fibrinolyse-hemmstoffen. Acta biol. med. germ 12: 522 1964;
  • 14 Marx R, Henning K. Über Verstärkersubstanzen der Antifibrinolysewirkung der Epsilon-aminocapronsquere im Organismus. Proceed. 8th Congr. Europ. Soc. Hemat. Karger, Basel 1962
  • 15 Bergehojf A, Glatzel H. Untersuchungen mit einem Plasmin-Präparat unter Verwendung des Kaseinspaltungstestes: Die Aktivität von Plasmin-Novo und seine Hemmbarkeit durch Epsilonaminocapronsäure und Trasylol. Thrombos. Diathes. haemorrh. (Stuttg.) 12: 418 1964;