What is fibrinogen (Fibrinogen)

From the Guidelines

Fibrinogen supplementation is recommended for patients with major bleeding accompanied by hypofibrinogenemia, with an initial dose of 3-4 g, as stated in the European guideline on management of major bleeding and coagulopathy following trauma: sixth edition 1.

Fibrinogen Replacement Therapy

When considering fibrinogen replacement therapy, it is essential to assess the patient's fibrinogen levels and overall coagulation status.

• Fibrinogen levels can be measured through a blood test, which is crucial for diagnosing bleeding disorders, monitoring disseminated intravascular coagulation (DIC), or assessing cardiovascular risk.
• Replacement therapy with cryoprecipitate or fibrinogen concentrate may be necessary for patients with dangerously low levels, typically when levels fall below 1.5 g/L in actively bleeding patients, as recommended by the European guideline 1.

Dosage and Administration

The recommended initial dose of fibrinogen supplementation is 3-4 g, which is equivalent to 15-20 single donor units of cryoprecipitate or 3-4 g fibrinogen concentrate, as stated in the European guideline 1.

• Repeat doses should be guided by viscoelastic tests and laboratory assessment of fibrinogen levels, to ensure that the patient's coagulation status is adequately addressed.

Clinical Considerations

Fibrinogen is a critical factor for hemostasis in the context of perioperative bleeding, and its deficiency can lead to impaired fibrin clot strength, as reported in a study published in the Journal of Thrombosis and Haemostasis 1.

• The usefulness of prothrombin complex concentrate (PCC) has been demonstrated in reducing haematoma formation in patients with head injury, and is preferable to fresh frozen plasma (FFP) for the rapid reversal of the effects of vitamin K antagonists (VKAs), as stated in the European guideline 1.

Monitoring and Adjustments

Viscoelastic tests, such as thromboelastometry, can be useful in guiding individualized goal-directed coagulation therapy in patients with traumatic coagulopathy, as recommended in the European guideline 1.

• It is essential to avoid the overly liberal use of PCC in trauma patients, as it may expose them to an increased risk of delayed thromboembolic adverse events, as reported in a study published in Critical Care 1.

From the FDA Drug Label

Fibrinogen (Factor I) is a soluble plasma protein that, during the coagulation process, is converted to fibrin, one of the key components of the blood clot. Normal plasma fibrinogen level is in the range of 200-450 mg/dL

The normal plasma fibrinogen level is between 200-450 mg/dL 2.

• Fibrinogen is a heterohexamer with a molecular weight of 340 kDa and composed of two sets of A alpha, B beta, and gamma polypeptide chains.
• The end product of the coagulation cascade is cross-linked fibrin which stabilizes the primary platelet plug and achieves secondary hemostasis 2.
• Administration of FIBRYGA to patients with congenital fibrinogen deficiency supplements the missing coagulation factor or increases low plasma fibrinogen levels 2.

From the Research

Fibrinogen Overview

• Fibrinogen plays a central role in coagulation, and low fibrinogen levels have been found to be risk factors for exaggerated bleeding, transfusion needs, and adverse outcomes 3.
• Fibrinogen supplementation may improve haemostatic function, as fibrinogen levels deteriorate before other routine coagulation parameters in trauma patients 4.

Indications for Fibrinogen Administration

• Fibrinogen administration is indicated in patients with severe trauma, cardiac surgery, postpartum hemorrhage, and liver transplantation 3, 5.
• Early administration of fibrinogen concentrate is associated with improved survival among severe trauma patients 4.
• Fibrinogen supplementation is recommended for treatment of severe trauma hemorrhage, but required dosages and aimed for post-treatment fibrinogen levels remain a matter of discussion 6.

Comparison of Fibrinogen Concentrate and Fresh Frozen Plasma

• Fibrinogen concentrate may be viewed as preferable to fresh frozen plasma or cryoprecipitate for fibrinogen supplementation 5.
• The evidence suggests that fibrinogen concentrate is superior to fresh frozen plasma in reducing blood loss, allogeneic transfusion requirements, length of intensive care unit and hospital stay, and increasing plasma fibrinogen levels 7.

Dosage and Post-Treatment Levels

• The required dosages of fibrinogen concentrate and aimed for post-treatment fibrinogen levels remain a matter of discussion 6.
• Post-treatment fibrinogen levels under 204.5 mg.dL-1 may predict the need for massive transfusion, and baseline fibrinogen/FibA10 levels should be considered for fibrinogen concentrate dosing 6.