The canonical role of the
hemostatic and fibrinolytic systems is to maintain vascular integrity. Perturbations in either system can prompt primary pathological end points of
hemorrhage or
thrombosis with vessel occlusion. However,
fibrin(
ogen) and
proteases controlling its deposition and clearance, including (pro)
thrombin and
plasmin(
ogen), have powerful roles in driving acute and reparative inflammatory pathways that affect the spectrum of tissue injury, remodeling, and repair. Indeed,
fibrin(
ogen) deposits are a near-universal feature of tissue injury, regardless of the nature of the inciting event, including
injuries driven by mechanical insult,
infection, or immunological derangements.
Fibrin can modify multiple aspects of inflammatory cell function by engaging leukocytes through a variety of cellular receptors and mechanisms. Studies on the role of coagulation system activation and
fibrin(
ogen) deposition in models of inflammatory disease and tissue injury have revealed points of commonality, as well as context-dependent contributions of coagulation and fibrinolytic factors. However, there remains a critical need to define the precise temporal and spatial mechanisms by which
fibrinogen-directed inflammatory events may dictate the severity of tissue injury and coordinate the remodeling and repair events essential to restore normal organ function. Current research trends suggest that future studies will give way to the identification of novel
hemostatic factor-targeted
therapies for a range of tissue
injuries and disease.