[The TAFI system. The new role of fibrinolysis].
The primary focus of the blood coagulation system is the prevention of blood loss. The system is regulated by various inhibitors, and by the fibrinolytic system, which removes the final product of the blood coagulation system, the fibrin clot. The fibrinolytic system is activated in the course of coagulation activation. The thrombin-activated fibrinolysis inhibitor (TAFI) is an important regulator of fibrinolysis. TAFI is activated by thrombin, and activation is enhanced in the presence of thrombomodulin. TAFIa, the product of TAFI activation, removes lysine residues from fibrin, which are essential for the binding of t-PA, plasminogen, and plasmin to fibrin. The fibrin loses its cofactor activity in t-PA-induced plasminogen activation, resulting in less plasmin, and the remaining plasmin finds less binding sites on fibrin, resulting in an increased resistance of the clot towards plasmin proteolysis. High concentrations of thrombin result in high TAFIa-activity and consequently in highly resistant fibrin clots. Patients with hyperprothrombinaemia consequently display elevated TAFIa-levels, which may contribute to the risk for thrombosis. Treatment with recombinant factor VIIa also leads to high concentrations of thrombin, resulting in fibrin clots with enhanced resistance towards fibrinolysis. At low thrombin concentration, as observed in patients with bleeding disorders or patients treated with anticoagulant drugs, less TAFIa is produced in the course of coagulation activation, and the clots are less resistant towards fibrinolysis. TAFIa-inhibitors are currently being developed for the treatment of throboembolic disorders or hypofibrinolytic DIC. Enhancement of TAFIa-activity may be helpful in patients with bleeding.
Dempfle
C-E
CE
Universitätsklinikum Mannheim, I. Medizinische Klinik, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim. carl-erik.dempfle@med.ma.uni-heidelberg.de
D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D025901:Carboxypeptidase B2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D013917:Thrombin / Q000502:physiology
D025901:Carboxypeptidase B2; D013917:Thrombin