Fibrinogen: the higher the better?

Abstract

Fibrinogen supplementation is commonly used to manage severe bleeding. Guidelines mostly recommend supplementation by cryoprecipitates or fibrinogen concentrates to maintain fibrinogen concentration above 1.5-2 g/L. However, evidence supporting these targets is weak and debates persist.

Fibrinogen plays a key role in hemostasis by forming clot fibrin network and promoting platelet aggregation. A decrease in fibrinogen concentration is a predictor of bleeding severity, particularly in surgery, postpartum hemorrhage and trauma. In vitro and clinical studies reported that low fibrinogen levels impair fibrin clot strength, and that clot strength is restored with fibrinogen repletion. All these data suggest that the higher the fibrinogen concentration, the better the management of bleeding. Nevertheless, randomized controlled trials have often failed to show significant benefits of fibrinogen supplementation during severe bleeding. Similarly, preemptive fibrinogen administration in surgery has shown no positive effect in patients without hypofibrinogenemia. These studies suggest that normal fibrinogen concentrations often remain sufficient to maintain clot function.

There are safety concerns with excessive fibrinogen supplementation. Elevated fibrinogen levels may promote thrombosis by enhancing clot density and resistance to breakdown. Some studies suggest a possible association between fibrinogen levels and adverse cardiovascular events. Costs are another issue.

In summary, current guidelines recommend target fibrinogen levels of 1.5-2 g/L during bleeding whereas higher targets are not supported due to lack of clinical benefit, cost, and potential risks. Further research is needed to optimize fibrinogen administration practices and evaluate their impact on clinical outcomes.