What is the treatment for fibrinogen deficiency?

Treatment of Fibrinogen Deficiency

For patients with fibrinogen deficiency, fibrinogen concentrate is the recommended first-line treatment, administered at a dose of 30-60 mg/kg to maintain fibrinogen levels above 1.0 g/L. 1

Types of Fibrinogen Deficiency

• Congenital deficiency: Rare genetic disorders (afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia)
• Acquired deficiency: More common, occurs in:
  • Massive hemorrhage/trauma
  • Liver disease
  • Disseminated intravascular coagulation (DIC)
  • Major surgery, particularly cardiac and liver procedures
  • Obstetric complications

Treatment Options

First-Line Treatment: Fibrinogen Concentrate

• Advantages:

  • Rapid and predictable increase in fibrinogen levels
  • Standardized fibrinogen content
  • Lower volume (50 ml vs 250 ml for cryoprecipitate)
  • No need for cross-matching
  • Viral inactivation/elimination steps 1
  • Effective for both congenital and acquired deficiencies 2, 3, 4

• Dosing:

  • Initial dose: 30-60 mg/kg 1
  • For surgical prophylaxis in congenital deficiency: median dose ~90 mg/kg for minor surgeries, higher doses for major surgeries 3
  • Target fibrinogen level: >1.0 g/L for active bleeding; higher targets (>1.5-2.0 g/L) may be needed for severe hemorrhage 1

Alternative Options

1. Cryoprecipitate:

   • Used when fibrinogen concentrate is unavailable
   • Rich in VWF, fibrinogen, and fibronectin
   • Disadvantages: requires thawing, larger volume, potential for transfusion reactions 1

2. Fresh Frozen Plasma (FFP):

   • Less effective than fibrinogen concentrate for correcting hypofibrinogenemia 1
   • Higher volumes required (at least 30 ml/kg) 1
   • Consider when multiple coagulation factor deficiencies are present

Monitoring and Efficacy Assessment

• Laboratory monitoring:

  • Plasma fibrinogen levels (target >1.0 g/L)
  • Viscoelastic testing (ROTEM/TEG) to assess functional fibrinogen contribution to clot strength 1
  • PT/aPTT to evaluate overall coagulation status

• Clinical efficacy:

  • Reduction in bleeding
  • Hemostatic success during surgical procedures
  • Studies show treatment success rates of 95-100% for bleeding episodes and surgical prophylaxis with fibrinogen concentrate 2, 4

Special Considerations

• Liver disease: While fibrinogen replacement may be needed for active bleeding, routine correction of fibrinogen deficiency for invasive procedures is discouraged 1

• Massive hemorrhage: Fibrinogen is often the first coagulation factor to reach critically low levels (<1.0 g/L) 1, 5

• Concomitant treatments:

  • Consider tranexamic acid in situations with hyperfibrinolysis
  • Correct hypocalcemia and hypomagnesaemia which often accompany massive transfusion 1

Potential Complications

• Thrombotic events (rare with modern concentrates)
• Allergic reactions
• Viral transmission risk is minimal with current manufacturing processes

Practical Algorithm

1. Assess fibrinogen level and clinical bleeding status
2. For active bleeding with fibrinogen <1.0 g/L:
   • Administer fibrinogen concentrate 30-60 mg/kg
   • Reassess fibrinogen level after administration
3. For surgical prophylaxis in congenital deficiency:
   • Calculate dose to achieve target fibrinogen level
   • Minor surgery: ~90 mg/kg
   • Major surgery: Higher doses, multiple infusions may be needed
4. If fibrinogen concentrate unavailable:
   • Use cryoprecipitate or high-dose FFP (30 ml/kg)

The evidence strongly supports fibrinogen concentrate as the preferred treatment for both congenital and acquired fibrinogen deficiencies due to its efficacy, safety profile, and practical advantages over alternative treatments.