A large dosage of urokinase combined with heparin was administered to a patient with arterial thrombosis of the leg. After a 3-day therapy with a dosage of 120,000 to 360,000 units per day, combined with 12,000 units heparin per day, the symptoms of arterial occulusion such as cyanosis, pain, coldness and disappearance of pulsation became worse. A larger dosage of 720,000 to 1,020,000 units urokinase per day, combined with 12,000 units heparin per day, was continued for 6 days and clinical symptoms were rapidly improved. In this period, urokinase was administered in the following two different ways: 360,000 or 720,000 units urokinase was infused within 2 or 4 hours, respectively, and 120,000 to 200,000 units urokinase was infused for following 20 hours. After a larger dosage of urokinase was administered, α
2-plasmin inhibitor, plasminogen and fibrinogen decreased and a prominent fibrinolytic effect was observed. Especially, α
2-plasmin inhibitor decreased more rapidly than other major inhibitor such as α
2-macroglobulin and α
1-antitrypsin, and its decrease was inversely correlated (r=-0.89) to the dosage of urokinase per hour. In addition, fibrinolytic effect became more prominent when the decrease of α
2-plasmin inhibitor approached 50%. It was concluded from these results that about 500,000 units urokinase per day as well as 100,000 units urokinase per hour were necessary for the treatment of arterial thrombosis.
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