The Mechanism of Enhanced Streptokinase‐Induced Clot Lysis following <i>In‐vitro</i> Factor‐XIII Inactivation

Abstract

S ummary . Factor‐XIII (fibrin stabilizing factor, FSF) activity in human plasma may be inhibited in vitro by a variety of sulphydryl inhibitors and by several derivatives of glycine. Incorporation of small amounts (40 units) of streptokinase (SK) into a clot formed from plasma after in vitro inactivation of Factor XIII, resulted in marked shortening of clot lysis times compared to controls without Factor‐XIII inactivation. Enhancement of SK‐induced clot lysis by the sulphydryl inhibitors is in part related to Factor‐XIII inactivation. Further acceleration of lysis is noted with concentrations greater than the minimal amount necessary for complete Factor‐XIII inhibition. At higher concentrations, clotting is delayed and ultimately completely inhibited. These reagents also produce marked changes on the thromboelastogram consistent with a weakened clot structure. No evidence to suggest increased plasminogen‐plasmin conversion, enhanced plasmin activity or inhibition of anti‐plasmin by sulphydryl inhibitors could be found. Glycine ethyl ester (GEE) incorporation results in marked enhancement of SK‐induced plasma clot lysis in vitro and pronounced changes on the thromboelastogram. The enhanced clot lysis is related to Factor‐XIII inhibition. No further acceleration of clot lysis was obtained once Factor‐XIII activity was completely inhibited. GEE alone shows an additional effect of inhibiting anti‐plasmin activity. Thus enhanced SK‐induced clot lysis following in vitro inhibition of Factor‐XIII activity with sulphydryl inhibitors and derivatives of glycine is considered to be due to the greater ease with which plasmin may act on a weakened clot. GEE, in addition to promoting the formation of a weaker clot, inhibits anti‐plasmin activity, and so further increases the relative effectiveness of streptokinase.