Blood Coagulation

Transglutaminase saves lives!

Blood clot formation is a vital process to prevent life-threatening blood loss after injuries. The plasmatic part of the blood coagulation cascade can be divided into three steps:

 

• Cascade leading to activation of prothrombin
• Fibrinogen (F004) activation by thrombin (T056) and fibrin aggregation (soft blood clot)
• Factor XIII activation by thrombin and cross-linking of fibrin fibers as well as covalent decoration with antifibrinolytics

Plasma transglutaminase factor XIII plays an essential role in blood clot formation. In addition, factor XIII is unique in this process, as all the other enzymes involved are proteases. Factor XIII renders the blood clot stiff and resistant to fibrinolytic degradation. Due to the fact that it is the only transglutaminase in the cascade, it offers the opportunity for a unique modulation of coagulation and, consequently promising new approaches e.g., to prophylaxis of thrombotic events in at-risk patients.

An excellent historical account of factor XIII in blood clotting is given by Laszlo Lorand: Factor XIII and the clotting of fibrinogen: from basic research to medicine. J. Thromb. Haemost. 2005, 3:1337-48.

Novel compounds developed by medicinal chemists at Zedira guide the way to small molecules selectively targeting coagulation factor XIII. In contrast to the currently available therapies, blocking factor XIII allows the formation of a weak fibrin clot. This prevents bleeding, lowering the risk of lifethreatening complications.