[Plasminogen activator of tissue type. Physiology, pathophysiology and clinical value]

Tissue-type plasminogen activator (t-PA), the major physiological activator of fibrinolysis, is contained in most human organs, tissues and secretions. t-PA is synthesized by endothelial cells and is released, in response to various stimuli, into the blood stream. Activation of plasminogen by t-PA is greatly enhanced in the presence of fibrin, whereby the fibrinolytic process is confined to the immediate environment of a formed thrombus. The enzymatic activity of t-PA is controlled by a fast-acting plasminogen activator inhibitor. Methods are now available for the immunological and functional determination of t-PA in biological fluids. The major function of plasmatic t-PA is the lysis of intravascular fibrin deposits. A reduced capacity to liberate functionally active t-PA from the vessel wall may result in the development of a thrombotic tendency. Extravascular t-PA is involved in various processes associated with cell migration and tissue remodelling. Purified t-PA preparations have been shown to induce marked fibrinolysis and thrombolysis with negligible fibrinogenolysis, in vitro and in various animal models. At present, the efficacy of recombinant t-PA in the lysis of arterial and venous thrombi is being tested in man.