Transglutaminase 2 contributes to the blood clotting cascade

Cross-linking of fibrin and associated proteins via Nε-(γ-glutamyl)lysine bonds in clot formation is a well-established component of the hemodynamic mechanism, providing clot rigidity and reducing the rate of fibrinolysis. The latter effect occurs predominantly through the incorporation of fibrinolytic inhibitors. To date, this function has been attributed exclusively to Factor XIIIa, also known as plasma transglutaminase (TG), one of eight identified in mammals. In this report, we demonstrate that tissue transglutaminase (TG2), a ubiquitous enzyme abundantly present in erythrocytes, also contributed to clot stabilisation. We observed clear differences between whole thrombi isolated from TG2-deficient and wild-type mice. Similarly, human thrombi were more stable in the presence of TG2 than when TG2 activity is specifically inhibited, revealing a previously unrecognized role for this enzyme in haemostasis. Therefore, we propose TG2 as an additional factor involved in blood coagulation.