Effects of urokinase on formation of .ALPHA. 2-AP-plasmin complex, fibrinogenolysis and on release of B.BETA.1(15)-42 in vivo.
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We have studied the effects of urokinase (UK) on concentration changes of α2-antiplasmin (α2-AP) and on fibrinogenolysis. Medium dose (480.000u) or large dose (960, 000u) of UK was given to each of seven normal volunteers by intravenous drip infusion within six hours, and then blood and urine analyses were carried out. Total α2-AP, which includes free α2-AP and α2-AP-plasmin complex, decreased about 50 per cent of the original value with large dose of UK. α2-AP-plasmin complex appeared in the plasma one hour after UK infusion and increased up to 50 per cent of total α2-AP at the end of UK infusion. Bβ1-42, which liberated from fibrinogen at the very early stage of fibrinogenolysis, increased significantly with UK infusion, and was 65 times as much as the normal range at the end of UK infusion. Urinary Bβ1-42 increased as well as plasma Bβ1-41. On the other hand, fibrinogen degradation products (FDP) measured with enzyme immunoassay (ETA) increased only slightly, and moreover, urinary FDP was not detectable at any time. Plasma fibrinogen level did not decrease and it changed within the normal range in both groups. We then gave 960, 000u of UK to three patients with deep vein thrombosis and blood analysis was carried out as with normal volunteers. The most significant observation different from that of normal volunteers was shown in FDP levels. Serum FDP levels of three patients increased significantly in comparison with normal volunteers. Urinary FDP increased as significantly as plasma FDP.In conclusion, we consider that infusion of 960, 000u of UK is enough to neutralyze α2-AP and enough to express thrombolytic activity. It causes only very early stage of fibrinogenolysis without advanced fibrinogenolysis which may result in bleeding tendency in normal volunteers. On the other hand, in thrombotic patients, advanced fibrinolysis was observed with UK infusion.
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