The fibrinolytic system: from Petri dishes to genetic engineering

M Verstraete - Thrombosis and haemostasis, 1995 - thieme-connect.com
M Verstraete
Thrombosis and haemostasis, 1995thieme-connect.com
That a blood clot dissolves spontaneously was described by Denys in 1889 (1); this
phenomenon was termed “fibrinolysis” by Dastre in 1893 (2) and a Belgian countryman,
Nolf, demonstrated in 1908 that not only blood coagulation but also fibrinolysis were
proteolytic processes (3). The Russian Yudin attracted much attention when he published
that cadaver blood can be used for transfusion purposes avoiding coagulation problems (4).
He very appropriately selected victims of accidents or sudden death to collect blood to be …
That a blood clot dissolves spontaneously was described by Denys in 1889 (1); this phenomenon was termed “fibrinolysis” by Dastre in 1893 (2) and a Belgian countryman, Nolf, demonstrated in 1908 that not only blood coagulation but also fibrinolysis were proteolytic processes (3). The Russian Yudin attracted much attention when he published that cadaver blood can be used for transfusion purposes avoiding coagulation problems (4). He very appropriately selected victims of accidents or sudden death to collect blood to be transfused long before it was known that sudden death is associated with an augmented endogenous fibrinolysis compared to those who die from chronic illness.
Fleisher and Loeb (5) published in 1915 that cells growing on plasma clots dramatically accelerate the clots’ liquefaction. Unfortunately, this observation was not pursued until the 1950’s when Astrup, a Danish investigator working at the Carlsberg Foundation in Copenhagen, prepared extracts from various organs and compared their fibrinolytic effect on clots (6). Another independent line of observations which ultimately led to the first thrombolytic drug started at the John Hopkins Medical School where Tillett, by mere chance observed in 1933 that filtrates of broth cultures of certain strains of hemolytic streptococci contained a substance capable of inducing the rapid fibrinolysis of human clots (7). He teamed up with a biochemist Gamer, who isolated the active principle, a protein with hydrolytic properties for fibrin which, in contrast to trypsin, would not degrade casein or gelatin (8). Tillett and Gamer first named the substance streptococcal fibrinolysis, namely a substance producing lysis of fibrin. The streptococcal protein was later coined streptokinase which strictly speaking is a misnomer because we now know that streptokinase is notan enzyme. Tillett also made the pertinent observation that the serum of patients recovering from streptococcal infections develops an inhibitor to
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