Study on the Effect of Streptokinase-Activated Plasmin (Fibrinolysin) on Clots in Various Stages of Organization12

Abstract

Venous clots were produced with I131-labeled fibrinogen in dogs at various time intervals and lysis measured continuously on an Esterline recorded by the method previously described (Ambrus, J. L., Back, N., Mihalyi, E., and Ambrus, C. M. Circulation Res. 1956 4, 430; Back, N., Ambrus, J. L. Goldstein, S., Harrisson, J. W. E., Circulation Res. 1956, 4, 440). Five daily treatments with 30 plasmin units (Loomis) per kg of human plasmin completely lysed clots less than 3 days old, but did not affect those older than 3 days. Histologic examination revealed that 3 days after formation, the clot is already largely separated from the blood stream by a layer of endo-thelial cells which may prevent plasmin from reaching clot. Increased clot density may also be a factor in the clot becoming resistant to treatment. In some instances, although the original radioactive clot completely disappeared, reformation of new nonradioactive thrombi took place. Trauma might have been a major cause of this phenomenon. Reformation of the clot occurred in spite of daily administrations of plasmin. This may be related to the developing resistance of the animal to this agent as shown by decrease in changes of the fibrinogen levels, clotting index and blood pressure response. On the basis of these findings, it seems that better therapeutic results may be expected from intravenous treatment with plasmin in acute rather than chronic thromboembolic disorders. In the latter, results would appear to depend on the degree of organization of the clot.