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Clot lysis rate, in presence or absence of vascular activator (VA) during clotting and in the surrounding medium, was studied. The mean fibrinolytic activity of plasma euglobulin fractions (EF) was 0,4 U UK/ml (measured on fibrin plates) in resting volunteers; it increased 6-8 fold ten min after the i.v. infusion of DDAVP (0,4 μg/kg). No activity was detectable in serum EF before and after DDAVP infusion, but, if plasma (10 mM citrate - 5 mM EDTA) was clotted by thrombin and the squeezed clot incubated in 0,017 M acetic acid, most of the activity could be recovered. This demonstrates that VA and intrinsic activator (s)(IA) bind to clots. 125I-fibrinogen labelled plasma and whole blood clots, obtained after DDAVP infusion, when incubated for 3 h at 37 °C in DDAVP serum showed 0% lysis, in normal plasma (containing weak IA activity) 15%, and in DDAVP-plasma 60% lysis. 30% lysis occurred when normal clots ware incubated in DDAVP-plasma. When DDAVP-plasma was clotted with thrombin (10 U/ml) in the presence of 0 to 20 mM Ca++, a striking inverse correlation (r=0,96) was observed between Ca++ concentration and lysis rate. The inhibitory effect of Ca++ may be due to cross-linkage of fibrin or to ↑ binding of α2-antiplasmin to fibrin.  These experiments demonstrate that physiological cone, of IA and of VA, bound to the clot during coagulation, do not induce efficient fibrinolysis in the presence of physiological Ca++ cone. Lysis takes place only when additional VA is present in the surrounding medium. This mechanism may be of physiological importance for the hemostasis-fibrinolysis balance in preventing premature lysis of formed fibrin, but assuring gradual fibrinolysis in the presence of ongoing release of VA fran vessel wall endothelium.

Higher Efficiency In Clot Lysis Rate Of Circulating Plasminogen Activators After DDAVP Infusion Compared To That Of Activators Bound To Clots