Thrombin activatable fibrinolysis inhibitor (TAFI): a molecular link between coagulation and fibrinolysis.
Although the maintenance of precise balance between coagulation and fibrinolysis is of utmost importance for normal haemostasis, until recently these two systems were considered as completely separate mechanisms involved in the process of formation and dissolution of blood clot. Thrombin activatable fibrinolysis inhibitor (TAFI) is a recently described attenuator of the fibrinolytic rate and is considered to be the molecular link between coagulation and fibrinolysis. TAFI circulates in plasma as an inactive precursor and its conversion in active enzyme (TAFIa) occurs by the action of thrombin or plasmin, but most efficiently by thrombin in the presence of its cofactor thrombomodulin. Once generated, TAFI down-regulates fibrinolysis by removing C-terminal lysine residues from partially degraded fibrin; thereby preventing the upregulation of plasminogen binding and activation. Because TAFI is activated by thrombin on one side, and acts as the attenuator of fibrinolysis on another side, it enables fine synchronization between these two systems. The antifibrinolytic function of TAFI mostly depends on TAFI concentration, the rate of its activation and the half-life of TAFIa in plasma. Changes in thrombin generation can have a profound effect on the rate of TAFI activation, and consequently on the rate of fibrinolysis. Therefore, it has been hypothesized that increased thrombin generation seen in thrombophilia patients may enhance TAFI activation, leading to a hypofibrinolytic state, which may further contribute to the thrombotic tendency. However, the results of several studies, in which relation between TAFI level and the occurrence of thromboembolic complications in carriers of hereditary thrombophilia have been investigated, were not consistent.
Miljić
Predrag
P
Institute of Haematology, Clinical Centre of Serbia, Belgrade, Serbia. pedra@beotel.rs
Heylen
Evelien
E
Willemse
Johan
J
Djordjević
Valentina
V
Radojković
Dragica
D
Colović
Milica
M
Elezović
Ivo
I
Hendriks
Dirk
D
D001777:Blood Coagulation / Q000502:physiology*; D025901:Carboxypeptidase B2 / Q000097:blood / Q000502:physiology*; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood
D025901:Carboxypeptidase B2