Role of coagulation factor XIII in fibrin clot structure and thrombosis

Clot formation within a blood vessel is the predominant cause of heart attacks, stroke and deep vein thrombosis. The clot is composed of a protein called fibrin which undergoes cross-linking by an enzyme called transglutaminase (factor XIII). The role of factor XIII in clot structure and thrombosis is not well understood. Our research is aimed at discovering how the thrombus is modulated by factor XIII, using model systems of clot formation, engineered proteins and in vivo models. This study will develop better understanding of processes involved in clot stability and in the future will help to design new anti-clotting drugs.

The thrombus is composed of a mesh of fibrin fibres, with platelets, erythrocytes and other cells embedded in this network. The clot is stabilised by cross-linking activity of transglutaminase FXIIIa. The effect(s) of cross-linking on fibrin clot structure and on risk for thrombosis are unknown. The aims of this project are to characterise 1) effects of cross-linking on fibrin structure and mechanisms by which effects occurs, 2) the relationship between fibrin cross-linking and FXIII activation, and 3) the contribution of cross-linking to in vivo thrombus formation. Understanding the mechanisms that regulate clot stability will facilitate discovery of new treatments for thrombosis.