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Tissue-type Plasminogen Activator (tPA)

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Fibrinolytics and Antifibrinolytics

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 146))

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Abstract

At the turn of this century, the Belgian physiologist Nolf (1908) observed that under certain experimental conditions the lysis of a blood clot could be obtained and introduced the concept of the “fourth state of blood coagulation,” namely the dissolution of thrombi. During the same period Loeb in Germany was studying the process of wound healing. He observed that epithelial cells were able to liquefy the fibrinous wound scab and thus assured their progression into the scab. He concluded that epithelial cells were able to produce “peptonizing enzymes” (Loeb 1904; Fleisher and Loeb 1915). In 1936, the Russian investigator Yudin (1936,1937) observed that cadaver blood was fluid and caused, after transfusion into man, a fibrinolytic state. In the 1930s and 1940s, Macfarlane and Biggs in Oxford were able to demonstrate, using a dilute plasma clot lysis assay, that several pathophysiological conditions triggered a release of fibrinolytic activity in man, such as surgery, trauma, physical exercise, mental stress, or the intravenous injection of adrenaline (MacFarlane 1937; MacFarlane and Biggs 1946; Biggs et al. 1947). During the same time period, Christensen and MacLeod (1945) discovered the zymogen plasminogen in human serum that could be activated by streptokinase (SK) to form active plasmin, and Astrup and collaborators started their seminal work on the fibrinolytic system at the Carlsberg Foundation Research Institute in Copenhagen. Astrup and Permin (1947) were the first investigators who clearly demonstrated that there exist two different plasminogen activators in mammalians, tPA and urokinase. Astrup and Müllertz (1952) also developed a sensitive test to measure the activity of tPA, the plasminogenenriched fibrin plate test.

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Bachmann, F. (2001). Tissue-type Plasminogen Activator (tPA). In: Bachmann, F. (eds) Fibrinolytics and Antifibrinolytics. Handbook of Experimental Pharmacology, vol 146. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56637-0_3

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