The level of extrinsic plasminogen activator (t-PA) during clotting as a determinant of the rate of fibrinolysis; inefficiency of activators added afterwards.

Dissolution of washed fibrin clots in vitro was found to depend on the concentration of extrinsic (tissue-type) plasminogen activator (t-PA) during clotting. Washed fibrin clots prepared from t-PA-rich plasma lyse spontaneously within a few hours, but similar clots, prepared from t-PA-poor plasma, do not lyse within 24 hours, neither spontaneously nor on addition of t-PA, streptokinase (SK) or urokinase (UK). When washed fibrin clots were suspended in buffered saline to which t-PA, SK or UK was added, lysis was enhanced by addition of lys-plasminogen to the buffer. This observation may have important consequences for the interpretation of fibrinolytic experiments in vitro and in vivo, for the management of a variety of diseases complicated by fibrin depositions, and eventually for thrombolytic therapy with t-PA.