ORIGINAL ARTICLESPlasma tissue-type plasminogen activator increases fibrinolytic activity of exogenous urokinase-type plasminogen activatorShenkman, Borisa; Livnat, Tamia; Budnik, Ivanb; Tamarin, Iliaa; Einav, Yuliac; Martinowitz, UrielaAuthor Information aLaboratory of Hemostasis, Institute of Thrombosis & Hemostasis, and the National Hemophilia Center, Chaim Sheba Medical Center, Tel-Hashomer, Israel bDepartment of Pathophysiology, Saratov State Medical University, Saratov, Russia cMathematical Biology Unit, Holon Institute of Technology, Holon, Israel Correspondence to Boris Shenkman, Laboratory of Hemostasis, Institute of Thrombosis & Hemostasis, and the National Hemophilia Center, Chaim Sheba Medical Center, Tel-Hashomer, Israel. Tel: +972 3 5302106; fax: +972 3 5351806; e-mail: [email protected] Received 15 February, 2012 Revised 22 July, 2012 Accepted 26 July, 2012 Blood Coagulation & Fibrinolysis: December 2012 - Volume 23 - Issue 8 - p 729-733 doi: 10.1097/MBC.0b013e32835897d5 Buy Metrics Abstract The relationship between tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) function is not fully understood. The aim of this study was to compare in vitro the fibrinolytic activity of tPA and uPA and evaluate their possible interaction. Blood coagulation and fibrinolysis were conducted by rotation thromboelastometry, whereas blood clotting was induced by CaCl2 and tissue factor and fibrinolysis additively by tPA and uPA. Effective concentration 50% of tPA and uPA fibrinolytic activity in blood was found to be 90 and 33 IU/ml relating to the units of activity established by manufacturers in the absence of blood. uPA-induced fibrinolysis in blood was faster compared with tPA used at the same units of activity. In contrast, in a blood-free system containing fibrinogen, plasminogen, and thrombin, fibrinolysis induced by uPA was weaker than by tPA. Treating of blood with tranexamic acid (60 mmol/l) was followed by decreased fibrinolytic potential of both exogenous tPA and uPA, despite uPA by itself is known to be not sensitive to aminocaproic acids. Thus, uPA exerted stronger activity in blood but weaker activity in blood-free system, compared with tPA. Taking into account the intermolecular binding of uPA to tPA, it could be suggested that interaction of exogenous uPA with plasma-containing tPA provided amplification of fibrinolysis due to formation of uPA/tPA complex possessing high affinity to fibrin. © 2012 Lippincott Williams & Wilkins, Inc.