title: Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Jerrold H
authors.initials: JH
authors.lastname: Levy
authors.forename: Ian
authors.initials: I
authors.lastname: Welsby
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Goodnough
mesh_terms: D005169:Factor VIII / Q000627:therapeutic use; D005340:Fibrinogen / Q000008:administration & dosage / Q000032:analysis / Q000502:physiology / Q000627:therapeutic use*; D006470:Hemorrhage / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D006487:Hemostasis; D006801:Humans; D019637:Orthopedic Procedures; D010949:Plasma; D014947:Wounds and Injuries / Q000188:drug therapy
chemical_list: C026912:cryoprecipitate coagulum; D005169:Factor VIII; D005340:Fibrinogen