Plasma tissue-type plasminogen activator increases fibrinolytic activity of exogenous urokinase-type plasminogen activator.
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.
Laboratory of Hemostasis, Institute of Thrombosis & Hemostasis, and the National Hemophilia Center, Chaim Sheba Medical Center, Tel-Hashomer, Israel. borshenk@sheba.health.gov.il
Boris
B
Shenkman
Tami
T
Livnat
Ivan
I
Budnik
Ilia
I
Tamarin
Yulia
Y
Einav
Uriel
U
Martinowitz
D002122:Calcium Chloride / Q000494:pharmacology; D002478:Cells, Cultured; D005337:Fibrin / Q000737:chemistry / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013916:Thrombelastography; D013917:Thrombin / Q000737:chemistry / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014148:Tranexamic Acid / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*; D014914:Whole Blood Coagulation Time
D014148:Tranexamic Acid; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D002122:Calcium Chloride