When is fibrinogen infusion recommended and what is the appropriate dose?

Fibrinogen Infusion: Indications and Dosing

Fibrinogen concentrate or cryoprecipitate should be administered when significant bleeding is accompanied by hypofibrinogenemia (plasma fibrinogen level ≤1.5 g/L or viscoelastic signs of functional fibrinogen deficit), with an initial dose of 3-4 g fibrinogen concentrate or equivalent cryoprecipitate (15-20 units). 1

Clinical Indications for Fibrinogen Replacement

Active Bleeding

• Administer fibrinogen when plasma levels fall below 1.5 g/L in actively bleeding patients 1, 2
• For massive hemorrhage with microvascular oozing or coagulation tests showing fibrinogen <1 g/L, provide aggressive replacement 1
• In trauma patients, early fibrinogen supplementation is recommended when hypofibrinogenemia is detected 1

Pregnancy and Obstetric Hemorrhage

• For pregnant women with congenital fibrinogen disorders:
  • Maintain fibrinogen levels ≥1 g/L throughout pregnancy 1
  • Target trough fibrinogen level of ≥1.5 g/L during labor and delivery 1
  • In case of vaginal bleeding or placental abruption, increase target to ≥1.5 g/L 1
• For obstetric hemorrhage with hypofibrinogenemia, fibrinogen concentrate offers rapid correction with minimal volume 3

Traumatic Brain Injury

• Patients with severe traumatic brain injury at high risk for hyperfibrinolysis benefit from fibrinogen concentrate administration 4
• Maintain fibrinogen levels ≥150 mg/dL in traumatic brain injury patients 4

Dosing Recommendations

Initial Dosing

• Fibrinogen concentrate: 3-4 g or 30-60 mg/kg 1, 2
• Cryoprecipitate: 15-20 units (equivalent to two pools) for a 70-kg adult 1, 2
• Fresh frozen plasma: If fibrinogen concentrate or cryoprecipitate unavailable, administer FFP at least 30 mL/kg for severe cases 1, 2

Monitoring and Subsequent Dosing

• Repeat fibrinogen levels after initial replacement to guide further therapy 1, 2
• For congenital disorders requiring long-term replacement:
  • Weekly trough measurements in the first month, then monthly 1
  • Pharmacokinetic study recommended when using plasma-derived concentrates 1
• In pregnancy with afibrinogenemia, expect increased dose requirements throughout pregnancy due to increased clearance 1

Advantages of Fibrinogen Concentrate vs. Cryoprecipitate

• Fibrinogen concentrate offers:
  • Rapid administration without thawing requirements 1, 5
  • Standardized dose in small volume 5
  • Pathogen inactivation as standard 5
  • More predictable fibrinogen increase 1, 5
• Cryoprecipitate contains additional coagulation factors but requires thawing and has greater preparation time 1, 2

Special Considerations and Pitfalls

Risk Assessment

• Monitor for thrombotic complications, especially in patients with history of thrombosis 2, 6
• In patients with both bleeding and thrombotic phenotypes, consider thromboprophylaxis alongside fibrinogen replacement 1
• For patients with afibrinogenemia type 2B or severe hypofibrinogenemia with history of thrombosis, provide thromboprophylaxis with adjusted fibrinogen replacement 1

Common Pitfalls

• Delaying fibrinogen replacement in actively bleeding patients 2
• Using inadequate doses of FFP (standard 15 mL/kg) in massive hemorrhage 1, 2
• Failing to recognize that fibrinogen is often the first coagulation factor to reach critical levels in massive bleeding 7
• Not considering that patients with Hb <10 g/dL have a high likelihood (89%) of low fibrinogen levels (<200 mg/dL) 7

Safety Profile

• Recent evidence suggests a favorable safety profile for fibrinogen concentrate in surgical patients 6
• Low incidence of thromboembolic events directly attributable to fibrinogen concentrate administration 6
• No specific risks beyond those associated with other blood components 1

Fibrinogen replacement should be guided by laboratory assessment or viscoelastic testing when available, but should not be delayed in cases of life-threatening bleeding with suspected hypofibrinogenemia 1, 2.