Factor XIII: driving (cross-)links in hemostasis, thrombosis, and disease

Abstract Blood clots are complex structures composed of blood cells and proteins held together by a structural framework provided by an insoluble fibrin network. Factor (F)XIII is a protransglutaminase essential for stabilizing the fibrin network. Activated FXIII(a) introduces novel covalent cross-links within and between fibrin and other plasma and cellular proteins and thereby promotes fibrin biochemical and mechanical integrity. These irreversible modifications are also major determinants of clot composition and functional properties. As such, FXIII has central roles in hemostasis and wound healing, thrombosis, and many proinflammatory diseases associated with coagulation activation. The biochemical properties of FXIII are as interesting as its biology is unusual, giving rise to unique and still undefined mechanisms. Here, we review features underlying FXIII biology, biochemical function, biophysical impact, and (patho)physiologic implications in hemostasis, thrombosis, and disease.