Characterization of thrombin activatable fibrinolysis inhibitor in normal and acquired haemostatic dysfunction

Area of Science:

• Biochemistry
• Hematology
• Physiology

Background:

• Thrombin activatable fibrinolysis inhibitor (TAFI) is a liver-synthesized proenzyme circulating at ~275 nmol/l.
• TAFI activation by thrombin or plasmin downregulates fibrinolysis by cleaving lysine/arginine residues from fibrin.
• The thrombin-thrombomodulin complex is the likely physiological activator of TAFI, with activated protein C modulating this activation.

Purpose of the Study:

• To investigate the role of TAFI in acquired coagulopathies, particularly in postpartum hemorrhage.
• To characterize the degree of TAFI activation using novel assays.
• To explore TAFI as a potential therapeutic target for postpartum hemorrhage.

Main Methods:

• Characterization of TAFI's enzymatic activity and activation pathways.
• Measurement of TAFI antigen levels in patient cohorts, including those with disseminated intravascular coagulation and postpartum hemorrhage.
• Development and application of specific assays to quantify TAFI activation.

Main Results:

• TAFI levels are reduced in disseminated intravascular coagulation.
• Significant reductions in TAFI levels are observed in women experiencing major postpartum hemorrhage requiring transfusion.
• New assays are being utilized to precisely characterize TAFI activation levels.

Conclusions:

• TAFI plays a crucial role in regulating fibrinolysis, balancing thrombosis and bleeding.
• Reduced TAFI levels in postpartum hemorrhage indicate its potential involvement in the pathophysiology of this condition.
• Further characterization of TAFI activation may lead to novel therapeutic strategies for managing postpartum hemorrhage and its associated morbidity.