Fibrinogen Supplementation and Its Indications

Abstract

Adequate plasma levels of fibrinogen are essential for clot formation, and in severe bleeding, fibrinogen reaches a critically low plasma concentration earlier than other coagulation factors. Although the critical minimum concentration of fibrinogen to maintain hemostasis is a matter of debate, many patients with coagulopathic bleeding require fibrinogen supplementation. Among the treatment options for fibrinogen supplementation, fibrinogen concentrate may be viewed by some as preferable to fresh frozen plasma or cryoprecipitate. The authors review major studies that have assessed fibrinogen treatment in trauma, cardiac surgery, end-stage liver disease, postpartum hemorrhage, and pediatric patients. Some but not all randomized controlled trials have shown that fibrinogen concentrate can be beneficial in these settings. The use of fibrinogen as part of coagulation factor concentrate based therapy guided by point-of-care viscoelastic coagulation monitoring (ROTEM [rotational thromboelastometry] or TEG [thromboelastography]) appears promising. In addition to reducing patients' exposure to allogeneic blood products, this strategy may reduce the risk of complications such as transfusion-associated circulatory overload, transfusion-related acute lung injury, and thromboembolic adverse events. Randomized controlled trials are challenging to perform in patients with critical bleeding, and more evidence is needed in this setting. However, current scientific rationale and clinical data support fibrinogen repletion in patients with ongoing bleeding and confirmed fibrinogen deficiency.

Defining trauma‐induced coagulopathy with respect to future implications for patient management: Communication from the SSC of the ISTH

“…22 Depletion is associated with poor outcomes, an effect which can be reversed with supplementation. 41 Low fibrinogen concentrations correlate with increased transfusions, ventilator days, and increased early and late mortality. 42 Fibrinogen supplementation improves clot initiation and stability, 43,44 and may decrease mortality in this group.…”

“…Coagulopathic patients can harbor hypofibrinogenemia early after injury, which can be a marker of TIC, and is dose‐dependently related to shock, injury severity, and mortality . Depletion is associated with poor outcomes, an effect which can be reversed with supplementation . Low fibrinogen concentrations correlate with increased transfusions, ventilator days, and increased early and late mortality .…”

Recent advances in use of fresh frozen plasma, cryoprecipitate, immunoglobulins, and clotting factors for transfusion support in patients with hematologic disease

“…Fibrinogen plays a central role in hemostasis as the substrate by which clots are formed. Deficiencies of a congenital or acquired nature have significant morbidity and mortality effects, and therefore supplementation is required in these patients [105 , 106] . Plasma and cryoprecipitate have both been used as replacement therapies for decades, but neither of these is ideal, requiring large volumes (less so in cryoprecipitate), risking pathogen infection, and requiring lengthy thawing [107 , 108] .…”

Hemostatic Balance in Severe Trauma

“…The importance of detecting and treating hypofibrinogenemia early was also investigated in a prospective cohort study of 517 adult trauma patients (42). Multiple studies have demonstrated evidence that hypofibrinogenemia is a critical issue in severe bleeding for pediatric intraoperative and trauma patients (43)(44)(45). One study in pediatric trauma patients analyzed an institutional transfusion protocol where cryoprecipitate was not included until the third transfusion package.…”