Human extrinsic plasminogen activator fibrinolytic properties and neutralization in vivo

The thrombolytic activity and elimination rate in vivo of a plasminogen activator purified from a melanoma cell line was examined in a rabbit thrombus model. Following an intravenous injection of 125I labelled plasminogen activator, its biological activity disappeared very rapidly from the plasma (t1/2 = 1.5 min) and radioactivity immediately accumulated in the liver. After a two-hour infusion with a total amount of 0.5 mg plasminogen activator a 60 per cent reduction in the weight of partially occluding thrombi was noted. No significant thrombolysis was seen in totally occluded vessels. Treatment with 0.5 mg plasminogen activator caused no depletion of fibrinogen or alpha 2-antiplasmin. No significant thrombolysis occurred after infusion of 0.5 mg streptokinase, but total lysis of occluding and non-occluding thrombi was obtained after a two-hour infusion of 1 mg streptokinase, without any reduction of fibrinogen. A marked reduction of alpha 2-antiplasmin was seen after both 0.5 and 1 mg of streptokinase treatment but were not seen in rabbits infused with plasminogen activator.