THE ROLE OF FIBRINOGEN IN ACUTE BLEEDING MANAGEMENT IN CFD

Fibrinogen is an essential plasma glycoprotein that supports hemostasis by enabling platelet aggregation and serving as the precursor to fibrin. During clot formation, thrombin converts fibrinogen into fibrin, which polymerizes and crosslinks to create a stable clot. This dual role of linking platelets and forming fibrin makes fibrinogen critical for effective clot integrity and wound healing.¹

A role in all steps of hemostatis¹

Primary hemostasis

Fibrinogen promotes platelet aggregation

Secondary hemostasis

Fibrinogen is converted into fibrin to form a fibrin mesh

Clot strength

Increases with fibrinogen concentration

Fibrinogen is the first clotting factor to reach critically low levels during acute bleeding episodes which compromises clot integrity.²

The coagulation cascade

Fibrinogen is a 340-kDa plasma glycoprotein synthesized in the liver^1,2

During coagulation, thrombin cleaves fibrinogen into fibrin monomers^1,2

Fibrin monomers polymerize into a fibrin network that stabilizes the platelet plug^1,2

This fibrin mesh is essential for clot integrity and resistance to fibrinolysis^1,3,4

Congenital Fibrinogen Deficiency (CFD)

What Causes CFD?

CFD includes 2 rare quantitative disorders: afibrinogenemia, marked by complete absence of fibrinogen, and hypofibrinogenemia, characterized by reduced levels of functional fibrinogen. Both result from mutations in the FGA, FGB, or FGG genes, affecting fibrinogen synthesis or secretion. Additionally, there are 2 qualitative disorders: dysfibrinogenemia, where fibrinogen is present but functionally impaired, and hypodysfibrinogenemia, where both functional and antigenic fibrinogen levels are discordantly reduced.⁵

Overview of CFD

The clinical severity of CFD is highly variable, ranging from asymptomatic to severe bleeding. Afibrinogenemia has the potential to cause life-threatening bleeding with a risk of thrombosis. Diagnosis relies on measuring fibrinogen activity and antigen levels, supported by genetic testing. Management of CFD centers on fibrinogen replacement to restore clotting capacity and prevent complications during bleeding episodes, surgery, or pregnancy.⁵

In 2024, there were an estimated 6585 individuals in the United States with CFD⁶

Afibrinogenemia: 367

Severe hypofibrinogenemia: 465

Moderate hypofibrinogenemia: 1564

Mild hypofibrinogenemia: 4189

Four types of CFD

Hypofibrinogenemia⁵

Quantitative
3 subtypes:
- mild (100 mg/dL to lower limit of normal value)*
- moderate (50 mg/dL to 90 mg/dL)*
- severe (< 50 mg/dL)*
Proportional decrease in functional and antigenic fibrinogen
Usually mild; major bleeding occurs with severe hypofibrinogenemia; fewer thrombotic events than with afibrinogenemia

Afibrinogenemia⁵

Quantitative
Complete absence of fibrinogen
Severe bleeding (umbilical stump, muscles), spontaneous splenic rupture, poor wound healing, bone cysts; thrombosis in large vessels possible

Dysfibrinogenemia⁵

Qualitative
Normal antigenic but decreased functional fibrinogen
Mild mucocutaneous bleeding, often triggered by surgery, trauma, or delivery; thrombotic phenotypes possible

Hypodysfibrinogenemia⁵

Qualitative and quantitative
Discrepant decrease in functional and antigenic fibrinogen
More symptomatic than dysfibrinogenemia, with a higher risk of bleeding and thrombosis

*Functional fibrinogen level

Low fibrinogen levels are associated with increased morbidity, mortality, and transfusion burden.⁷

The clinical impact

Get more information about CFD, management options, and treatment advancements.

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References

Ikić V. Fibrinogen and bleeding in adult cardiac surgery: a review of the literature. Surgeries. 2021;2:409–436.
Grottke O, Mallaiah S, Karkouti K, Saner F, Haas T. Fibrinogen supplementation and its indications. Semin Thromb Hemost. 2020;46(1):38-49.
Rossaint R, Afshari A, Bouillon B, et al. The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition. Crit Care. 2023;27(1):80.
Boer C, Meesters MI, Milojevic M, et al. 2017 EACTS/ EACTA Guidelines on patient blood management for adult cardiac surgery. J Cardiothorac Vasc Anesth. 2018; 32(1): 88-120.
May JE, Wolberg AS, Lim MY. Disorders of fibrinogen and fibrinolysis. Hematol Oncol Clin North Am. 2021;35(6):1197-1217.
Data on file, Grifols.
McQuilten ZK, Wood EM, Bailey M, Cameron PA, Cooper DJ. Fibrinogen is an independent predictor of mortality in major trauma patients: A five-year statewide cohort study. Injury. 2017;48(5):1074-1081.