Investigations on the Inhibitors of the Fibrinolytic System

Summary

Anti-plasmin and anti-urokinase activity of plasma was investigated with a method using preformed ¹³¹I-labelled clots. The inhibition of plasmin by plasma was found to be produced partly by direct and partly by slow progressive inactivation, while the results did not support the supposition that the anti-plasmin-plasmin complex is reversible in the presence of fibrin.

It was found that thrombocytes contain very little anti-plasmin, and that heparin in a concentration as occurs during anticoagulant therapy does not influence the anti-plasmin nor the anti-urokinase activity of the plasma.

The results provide evidence that urokinase and blood activator are not identical substances and it is concluded that estimation of the anti-urokinase activity will not produce an index for the presence of an inhibitor of the blood activator.

• References

• 1 Alkjaersig N. The antifibrinolytic activity of platelets. In: Henry Ford Hospital Symposium: Blood platelets, p. 329. Boston, 1961
• 2 Alkjaersig N, Fletcher A. P, Sherry S. The activation of human plasminogen. I. Spontaneous activation in glycerol. J. biol. Chem. 233: 86 1958;
• 3 Ambrus G. M, Back N, Ambrus J. L. On the mechanism of thrombolysis by plasmin. Circulat. Res. 10: 161 1962;
• 4 Dudok de Wit C, Krijnen H. W, den Ottolander G. J. H. The measurement of fibrinolytic activity with ¹³¹I-labeled clots. I. Methods. Thrombos. Diathes. haemorrh. (Stuttg.) 8: 315 1962;
• 5 Johnson S. A, Schneider G. L. The existence of antifibrinolysin activity in platelets. Science 117: 229 1953;
• 6 Kline D. L, Fishman J. B. Improved procedure for the isolation of human plasminogen. J. biol. Chem. 236: 3233 1961;
• 7 Konttinen Y. The effect of heparin on the fibrinolytic activity of streptokinase-activated human plasma. Scand. J. clin. Lab. Invest. 14: 15 1962;
• 8 Nilsson I. M, Krook P.L, 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;
• 9 Norman P. S, Hill B. M. Studies of the plasmin system. III. Physical properties of the two plasmin inhibitors in plasma. J. exp. Med. 108: 639 1958;
• 10 Ploug J, Kjeldgaard N. O. Urokinase. An activator of plasminogen from human urine. I. Isolation and properties. Biochim. biophys. Acta (Amst.) 24: 278 1957;
• 11 Sherry S, Lindemeyer R. I, Fletcher A. P, Alkjaersig N. Studies on enhanced fibrinolytic activity in man. J. clin. Invest. 38: 810 1959;
• 12 Stefanini M, Murphy I. S. Studies on platelets XIV. Human platelets as source of antifibrinolysin. J. clin. Invest. 35: 355 1956;
• 13 Vries S. I. de, Braat-van Straaten M. A. J, Millier E, Wettermark M. Antiplasmin deficiency in polycythaemia: a form of thrombopathy. Thrombos. Diathes. haemorrh. (Stuttg.) 6: 445 1961;