Accelerated Lysis of Blood Clots

Abstract

IN a recent article¹, we described a class of compounds which specifically inhibited cross-linking of the sub-units of the clot network. The possibility arose that clot lysis by the proteolytic enzyme system of blood (plasmin) might be greatly enhanced if clotting were allowed to take place in the presence of the foregoing inhibitors, of which glycineamide is a simple example. (Of eight glycyl dipeptides so far examined, only those of L-isoleucine, L-valine and glycine showed appreciable effect, emphasizing the specific nature of the inhibition of cross-linking of the clot (unpublished data by L. Lorand and K. Konishi).) In order to test the effect of this substance on clot lysis, the following experiment was performed. 0.8 ml. aliquots of freshly drawn (cubital vein) human blood was mixed in glass tubes: (a) with 0.1 ml. of 0.2 M neutral glycineamide and 0.1 ml. of purified urokinase (a gift from Abbott Laboratories, North Chicago, Illinois) containing 90 units of the plasminogen activator in 0.15 M neutral sodium chloride; (b) with 0.1 ml. each of 0.2 M glycineamide and 0.15 M sodium chloride; (c) with 0.1 ml. each of neutral 0.2 and 0.15 M sodium chloride solutions; and finally (d) with 0.1 ml. of 0.2 M sodium chloride and 0.1 ml. of the urokinase solution containing 90 units of activity.