[Thrombin activatable fibrinolysis inhibitor (TAFI) and its importance in the regulation of fibrinolysis].
Thrombin activatable fibrinolysis inhibitor (TAFI) also named procarboxypeptidase U (CPU), procarboxypeptidase R (CPR) and plasma procarboxypeptidase B (CPB) provides an important link between fibrinolysis and coagulation cascade. Activated TAFI (TAFIa) reduces a generation of plasmin because it cleaves off the carboxy-terminal lysine residues from partially degraded fibrin and thereby abrogates the fibrin cofactor function in the tPA-mediated catalysis of plasminogen to plasmin. TAFI is activated by thrombin-thrombomodulin complex. TAFI transformation to the activated TAFI (TAFIa) induced by thrombin supports the important role of coagulation cascade in regulation of fibrinolysis. This can be proved by a fact that the patients with a factor XI (FXI) deficiency are prone to bleeding from tissues with a high local fibrinolytic activity (urinary tract, nose, oral cavity, tonsils) that can be explained by a decreased thrombin-mediated TAFI activation. On the other hand the prothrombotic mutation of factor V (FV Leiden) associated with a resistance to activated protein C (APC-resistance) possess both mechanisms-an increased thrombin generation in coagulation cascade and a down regulation of fibrinolysis by a way of the thrombin-induced TAFI activation. For the future an inhibition of TAFI (e.g. by FXI inhibitors) offers the therapeutic possibilities to improve the decreased fibrinolysis and increase the efficiency of fibrinolytic therapy in thrombotic disorders. In bleeding disorders (hemophilia A, B) the drugs with a higher efficiency of TAFI for down regulation of an increased fibrinolysis could be used.
Stasko
J
J
Klinika hematológie a transfuziológie Jesseniovej lekárskej fakulty UK a Martinskej FN a Národné centrum hemostázy a trombózy Martinskej FN, Martin, Slovenská republika.
Hudecek
J
J
Kubisz
P
P
D001777:Blood Coagulation / Q000502:physiology; D001778:Blood Coagulation Disorders / Q000097:blood / Q000503:physiopathology; D025901:Carboxypeptidase B2 / Q000502:physiology*; D005342:Fibrinolysis / Q000502:physiology*; D006474:Hemorrhagic Disorders / Q000097:blood / Q000503:physiopathology; D006801:Humans
D025901:Carboxypeptidase B2