Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy

Fibrinogen plays a critical role in achieving and maintaining hemostasis and is fundamental to effective clot formation. There is increasing awareness of the important role of fibrinogen as a key target for the treatment and prevention of acquired bleeding. Fibrinogen is the first coagulation factor to fall to critically low levels (<1.0 g/L) during major hemorrhage (normal plasma fibrinogen levels range from 2.0 to 4.5 g/L), and current guidelines recommend maintaining the plasma fibrinogen level above 1.5 g/L. Fibrinogen supplementation can be achieved using plasma or cryoprecipitate; however, there are a number of safety concerns associated with these allogeneic blood products and there is a lack of high‐quality evidence to support their use. Additionally, there is sometimes a long delay associated with the preparation of frozen products for infusion. Fibrinogen concentrate provides a promising alternative to allogeneic blood products and has a number of advantages: it allows a standardized dose of fibrinogen to be rapidly administered in a small volume, has a very good safety profile, and is virally inactivated as standard. Administration of fibrinogen concentrate, often guided by point‐of‐care viscoelastic testing to allow individualized dosing, has been successfully used as hemostatic therapy in a range of clinical settings, including cardiovascular surgery, postpartum hemorrhage, and trauma. Results show that fibrinogen concentrate is associated with a reduction or even total avoidance of allogeneic blood product transfusion. Fibrinogen concentrate represents an important option for the treatment of coagulopathic bleeding; further studies are needed to determine precise dosing strategies and thresholds for fibrinogen supplementation.