Makindo Medical Notes

Fibrinogen has two main roles: (1) as the substrate for fibrin formation and (2) as a ligand for the platelet aIIβIII receptor, promoting platelet aggregation.

About

• Fibrinogen (Factor I): A clotting factor found in high concentrations in plasma, playing a crucial role in blood clot stabilization and haemostasis.
• It is converted to fibrin by thrombin, forming a stable blood clot and helping to stop bleeding.
• Beyond haemostasis, fibrinogen is involved in thrombosis, host defense, inflammation, and wound healing processes.

Aetiology

• Genetic Encoding: Fibrinogen is encoded by three genes located on chromosome 4:
  • Aa (FGA)
  • B Beta (FGB)
  • Gamma (FGG)
• It is a glycoprotein produced primarily by the liver and secreted into the bloodstream both basally and in response to stimuli.
• Supports platelet aggregation by binding to the platelet aIIβIII receptor.

Clinical Significance

• Low fibrinogen levels lead to an increased risk of bleeding and impaired clot formation.
• Elevated fibrinogen levels can contribute to thrombotic events, as fibrinogen is an acute phase reactant and may rise during inflammation, infection, or tissue injury.

Investigations

• Normal Range: Plasma fibrinogen levels are typically between 2-4 g/L.
• Elevated Fibrinogen: Can act as an acute phase reactant, with levels increasing in response to inflammation, infection, or trauma.
• Decreased Fibrinogen: Occurs due to:
  • Haemorrhage
  • Haemodilution (e.g., due to excessive IV fluids)
  • Sepsis
  • Consumption in conditions like DIC (Disseminated Intravascular Coagulation) and thrombosis
  • Congenital disorders, including:
    • Afibrinogenaemia: Complete absence of fibrinogen, leading to severe bleeding tendencies.
    • Hypofibrinogenaemia: Reduced levels of fibrinogen, causing mild to severe bleeding, depending on the fibrinogen concentration.
    • Dysfibrinogenaemia: Normal fibrinogen levels, but with functional abnormalities impairing clot formation.

Pathology

• Fibrinogen Deficiency: Can lead to uncontrolled bleeding and haemorrhagic complications.
• Thrombosis Risk: Elevated fibrinogen levels contribute to thrombosis and may indicate an underlying inflammatory or hypercoagulable state.

Management

• Replacement Therapy: Fibrinogen replacement can be provided via fresh frozen plasma (FFP) or cryoprecipitate (usually 10 units).
• Target Levels: The target fibrinogen level in bleeding patients is generally ≥ 1 g/L.
• Fibrinogen Concentrate: Fibrinogen can be administered as a medication; consult the BNF for guidelines.

References

• Wiley Online Library - Fibrinogen