Urokinase in the Management of Acute Arterial and Venous Thrombosis

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


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