Relation of the fibrinolytic mechanism to other proteolytic systems in plasma

I shall first try to illustrate the close integration of the fibrinolytic system with other proteolytic processes in blood, by recalling some of the efforts to segregate it from the intrinsic plasma kinin forming system. Attempts at clear chemical distinction between plasmin and the specific kininogenases were complicated by two factors: (1) the activities associated with plasmin resided possibly in more than one molecular species (Markus & Ambrus 1960); (2) plasma kininogenases were distinguished from plasmin only by minor quantitative or by negative criteria. The kininogenases act only on natural or synthetic substrates which are attacked by plasmin as well. The active centre of plasma kininogenase differs from that of plasmin mainly by the substrates which it does not attack. Its constitution is probably very similar to the centres of plasmin, thrombin, trypsin and chymotrypsin. Clearer differences appeared when the activation of the pre-active enzymes in human plasma was considered (Eisen 1963). Figure 1 shows that streptokinase levels activating all plasminogen in human plasma induced much smaller kinin formation than did glass powder. Yet, when clotted, the first plasma lysed in a few seconds, and the other in more than 24 hours. Similarly, the small kinin formation resulting from the complete activation by streptokinase, was greatly enhanced when activation by glass or kaolin was superimposed in the same plasma sample.