Fibrinolysis. VIII. Comparative study in vitro of the effects of various proteolytic agents on the blood clotting mechanism of human plasma.

Abstract

Abstract Nine enzymatic agents of different source and of different degree of purification were investigated with reference to their effect on the clotting mechanism and for their esterase activity in vitro. Comparable concentrations were used on the basis of the caseinolytic activity of each agent. The effects of the various materials were related, as expected, to the dose used. At a dose of 20 × 10 −3 caseinolytic units per milliliter all agents shortened the partial thromboplastin time. Some preparations (trypsin and protease, a bacterial agent) accelerated also the generation of thromboplastin and of thrombin. On the other hand, Aspergillin O, PK (a bacterial endopeptidase), and rhozyme A-4 (another fungal product from Aspergillus oryzae and niger) delayed the generation of thrombin. Aspergillin O and PK exhibited antithrombin III activity, while rhozyme A-4 delayed the plasma prothrombin time, presumably through the release of antithrombin VI activity. The effect of all enzymes of individual clotting agents was negligible unless high concentrations were used. On the basis of these studies, PK, Aspergillin O, and, to a lesser extent, rhozyme A-4 offered, promise as fibrinolytic agents because of their clot delaying effect associated with high fibrinolytic activity.