What is the role of fibrinogen concentrates in trauma patients with coagulopathy?

From the Guidelines

Fibrinogen concentrates are recommended for trauma patients with significant bleeding who have evidence of fibrinogen deficiency, typically defined as plasma fibrinogen levels below 1.5 g/L, as guided by the most recent European guideline on management of major bleeding and coagulopathy following trauma: sixth edition 1. The standard dosing is 25-50 mg/kg, administered intravenously as soon as possible after identifying hypofibrinogenemia. For an average adult, this translates to approximately 2-4 grams of fibrinogen concentrate. Administration should be guided by thromboelastography (TEG) or rotational thromboelastometry (ROTEM) when available, as these tests provide rapid assessment of clot formation and strength, as suggested by the European guideline 1. Some key points to consider when using fibrinogen concentrates in trauma patients include:

• Fibrinogen is essential for clot formation as it converts to fibrin and provides the structural framework for blood clots.
• Maintaining adequate fibrinogen levels helps control bleeding, reduce transfusion requirements, and potentially improve survival in severely injured trauma patients.
• The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition 1 provides the most up-to-date recommendations for the use of fibrinogen concentrates in trauma patients.
• Other studies, such as those published in the Journal of Thrombosis and Haemostasis 1 and Intensive Care Medicine 1, provide additional information on the use of fibrinogen concentrates, but the European guideline 1 is the most recent and highest quality study. Repeat dosing may be necessary based on ongoing bleeding and follow-up fibrinogen levels, as determined by the individual patient's needs and response to treatment. It is also important to note that the use of prothrombin complex concentrate (PCC) may be considered in certain situations, such as when the patient has a prolonged EXTEM clotting time despite a fibrinogen level > 1.5 g/L, as suggested by the European guideline 1. However, the primary focus should be on maintaining adequate fibrinogen levels to support clot formation and control bleeding. Overall, the use of fibrinogen concentrates in trauma patients with significant bleeding and evidence of fibrinogen deficiency is a critical component of trauma care, and should be guided by the most recent and highest quality evidence, such as the European guideline on management of major bleeding and coagulopathy following trauma: sixth edition 1.

From the FDA Drug Label

FIBRYGA is a human fibrinogen concentrate indicated for: • fibrinogen supplementation in bleeding patients with acquired fibrinogen deficiency • treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia

The FDA drug label indicates that fibrinogen concentrates, such as FIBRYGA, can be used for fibrinogen supplementation in bleeding patients with acquired fibrinogen deficiency. This includes trauma patients who may experience bleeding due to acquired fibrinogen deficiency.

• The recommended dose for adults with acquired fibrinogen deficiency is 4g.
• For adolescents age ≥ 12 years, the recommended dose is 50 mg/kg body weight.
• For children age <12 years, the recommended dose is 70 mg/kg body weight.
• Additional doses may be administered as needed to bleeding patients when plasma fibrinogen level is ≤200 mg/dL or thromboelastometry FIBTEM A10 is ≤10 mm (or equivalent values generated by other viscoelastic testing methods) 2.

It is essential to note that the use of fibrinogen concentrates in trauma patients should be guided by the patient's clinical condition, plasma fibrinogen levels, and viscoelastic testing results. The benefits of administration versus the risks of thrombosis should be carefully weighed 2.

From the Research

Fibrinogen Concentrates in Trauma Patients

• Fibrinogen supplementation is essential for clot formation, and in severe bleeding, fibrinogen reaches a critically low plasma concentration earlier than other coagulation factors 3
• Fibrinogen concentrate may be viewed as preferable to fresh frozen plasma or cryoprecipitate for fibrinogen supplementation in trauma patients 3
• The use of fibrinogen as part of coagulation factor concentrate-based therapy guided by point-of-care viscoelastic coagulation monitoring appears promising in reducing patients' exposure to allogeneic blood products and the risk of complications 3

Efficacy and Tolerability of Fibrinogen Concentrate

• Fibrinogen concentrates have been shown to improve laboratory measures of coagulation and may be life-saving in patients with acquired hypofibrinogenemia and severe bleeding 4
• A study found that after a median dose of 4 g of fibrinogen concentrate, a mean absolute increase of 1.09 g/l in plasma fibrinogen was measured, and coagulation parameters were significantly improved 4
• Mortality rates of 32.3% and 44.2% were reported after 24 h and 72 h, respectively, in patients treated with fibrinogen concentrates 4

Fibrinogen Levels in Trauma Patients

• A retrospective study found that fibrinogen concentrate therapy did not lead to higher fibrinogen levels post-trauma beyond that occurring naturally due to the acute phase response 5
• The study also found that inflammatory parameters were generally lower in controls, and the rise of fibrinogen levels from day 2 onwards can be attributed to an upregulated fibrinogen synthesis in the liver 5
• Another study found that fibrinogen concentrates, but not fresh frozen plasma, corrected low fibrinogen concentrations following in vitro haemodilution 6

Management of Hypofibrinogenemia in Trauma

• Hypofibrinogenemia is an important cause of nonanatomic bleeding in trauma, and the cornerstone of treatment remains fibrinogen replacement with cryoprecipitate or fibrinogen concentrates 7
• An evidence-based threshold for fibrinogen replacement is not well established, but expert opinion recommends maintaining a level above 150 mg/dl 7
• The Clauss fibrinogen assay is the gold standard test for fibrinogen levels, although viscoelastic hemostatic assays are often used when a lab delay is anticipated 7