Some Complexities of Multiple Inhibitor Interactions in Fibrinolytic Systems

SummaryHuman or canine fibrin polymers which are structurally altered by the combined action of plasmin and EACA show an increased resistance to digestion by trypsin, but not to digestion by chymotrypsin. These observations support the concept that EACA inhibition of fibrinolysis is to a variable extent a function of structural changes in the substrate, and that the changes may be related to the susceptibility of lysyl- and arginyl-sites attacked by plasmin and trypsin, but not by chymotrypsin.In plasma, the fibrin modification reactions mediated by plasmin + EACA are analogous to those in purified systems, with quantitative differences resulting from the presence of other inhibitors, and perhaps from earlier gelation of the developing polymers.This complexity of the action of EACA must be taken into account in comparing its effects with those of other inhibitors, which also have variable and non-linear effects related to prevention of autodigestion of plasmin, antagonistic or potentiative combinations of inhibitors, and interference with substrate conversion.