Laboratory control of urokinase therapy at low or moderate dosages. An in-vitro study

In vitro thrombolytic experiments were performed in a system composed of a radioactive clot (125I fibrinogen) perfused by whole anticoagulated blood to which a small amount of urokinase (UK) was added by continuous infusion. At various intervals a small aliquot of blood was drawn from the system and assayed for fibrinogen, plasminogen and alpha 2-antiplasmin. Results were correlated with the degree of thrombolysis measured continuously as decrease of clot radioactivity by a ratemeter connected to a recorder. The coefficients of correlation between fibrinogen, plasminogen and thrombolysis were -0.45 and -0.46, respectively (p less than 0.001). The highest coefficient of correlation was observed between alpha 2-antiplasmin change and thrombolysis (-0.84; p less than 0.001). Results indicate that the initiation of an effective thrombolytic state induced by UK required the depletion of about 50% of alpha 2-antiplasmin. The measurement of alpha 2-antiplasmin during UK therapy at low or moderate dosage appears to be useful for dosage adjustments leading to the development of a thrombolytic state.