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.

Cryoprecipitate transfusion: current perspectives

“…37 These results and others from previous RCTs of fibrinogen concentrate in surgery summarized by Levy et al 38 do not highlight any thrombotic or safety concerns with fibrinogen concentrate. Further safety and adverse event data should become available for cryoprecipitate and fibrinogen concentrate with increased clinical experience and trials of fibrinogen replacement in active hemorrhage.…”

Monitoring the coagulation status of trauma patients with viscoelastic devices

“…There have been a number of reports on the relationship between the test results obtained by viscoelastic devices and outcome in trauma patients [28][29][30][31]. One study reported that mortality was 100% in patients manifesting fulminant hyperfibrinolysis with a mean injury severity score (ISS) of The lower right window shows a graph presenting the time course of thrombus formation in which the horizontal axis is time and the vertical axis is the measured pressure.…”

Context-dependent risks and benefits of transfusion in the critically ill

“…45 Because FFP is associated with a significant number of side effects (Table 4), in particular transfusion-related acute lung injury, 55 recent studies have explored the possibility of using empirical fibrinogen concentrate or cryoprecipitate to replace FFP in critical bleeding. 56,57 Indeed, plasma fibrinogen concentration appears to be first coagulation factor to be depleted in trauma-acquired coagulopathy. 58 RCTs on early use of fibrinogen concentrate (60-70 mg/kg) in trauma-or surgery-induced hemorrhage are already under way, 59,60 and if the results are positive, a reduction in the usage of FFP in critical bleeding is anticipated.…”