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December 1968

Urokinase in the Management of Acute Arterial and Venous Thrombosis

Author Affiliations

Durham, NC
From the Department of Surgery, Duke University Medical Center, Durham, NC.

Arch Surg. 1968;97(6):910-916. doi:10.1001/archsurg.1968.01340060088009

ALTHOUGH fibrinolysis was recognized by Denis in 18381 and Dastre used the term "fibrinolysis" in 1893,2 it was not until 1933, when Tillet and Garner3 demonstrated that filtrates of strains of β-hemolytic strptococci were capable of liquifying human fibrin clots, that induced thrombolysis became a possibility. In recent years, a variety of proteolytic enzymes, plasminogen activators, and plasmin (as well as mixtures of these agents) have been used to induce thrombolysis with unpredictable results and frequent undesirable reactions. A fibrinolytic agent which acted predictably and was nontoxic was needed.

The fibrinolytic activity of urine was noted by Macfarlane and Pilling in 1947.4 Subsequent investigators have shown that the fibrinolytic activity of urine is due to an activator (urokinase) of plasminogen,5 that the activator can be extracted in a relatively pure state,6 and that the activator is nontoxic and nonantigenic. This pedigree suggested that urokinase

von Kaulla, cited by Denis, P.S.: Chemistry of Thrombolysis: Human Fibrinolytic Enzymes , Springfield, Ill: Charles C Thomas, Publisher, 1963, p 9.
von Kaulla, cited by Dastre, A.: Chemistry of Thrombolysis: Human Fibrinolytic Enzymes , Springfield, Ill: Charles C Thomas, Publisher, 1963, p 10.
Tillet, W.S., and Garner, R.L.:  The Fibrinolytic Activity of Hemolytic Streptococci , J Exp Med 58:485-502 ( (Oct) ) 1933.Article
Macfarlane, R.G., and Pilling, J.:  Fibrinolytic Activity of Normal Urine , Nature 159:779 ( (June) ) 1947.Article
Astrup, T., and Sterndorff, I.  An Activator of Plasminogen in Normal Urine , Proc Soc Exp Biol Med 81:675-678 ( (Dec) ) 1952.Article
Celander, D.R., and Guest, M.M.:  The Biochemistry and Physiology of Urokinase , Amer J Cardiol 6:409-419 ( (Aug) ) 1960.Article
Astrup, T., and Müllertz, S.:  The Fibrin Plate Method for Estimating Fibrinolytic Activity , Arch Biochem 40:346-351 ( (Sept) ) 1952.Article
Silver, D., and Anlyan, W.G.:  Fibrinolysin Therapy—A Surgical Adjunct , Rev Surg 19:401-407 ( (Nov) -Dec) 1962.
Fletcher, A.P., et al:  The Devlopment of Urokinase as a Thrombolytic Agent: Maintenance of a Sustained Thrombolytic State in Man by its Intravenous Infusion , J Lab Clin Med 65:713-731 ( (May) ) 1965.
Tow, D.E., et al:  Urokinase in Pulmonary Embolism , New Eng J Med 277:1161-1167 ( (Nov) ) 1967.Article
Sasahara, A.A., et al:  Urokinase Therapy in Clinical Pulmonary Embolism: A New Thrombolytic Agent , New Eng J Med 277:1168-1173 ( (Nov) ) 1967.Article