How to manage low fibrinogen (hypofibrinogenemia)?

Management of Hypofibrinogenemia

For patients with hypofibrinogenemia, fibrinogen replacement should be initiated when levels fall below 1.5 g/L in actively bleeding patients, using cryoprecipitate or fibrinogen concentrate to restore hemostatic function. 1

Diagnostic Approach

• Hypofibrinogenemia is defined as decreased levels of functional fibrinogen, with severity classified as:

  • Severe: fibrinogen level <0.5 g/L 1
  • Moderate: fibrinogen level between 0.5-0.9 g/L 1
  • Mild: fibrinogen level between 1 g/L and lower limit of normal 1

• Regular monitoring of fibrinogen levels is essential, particularly in patients with active bleeding, using either:

  • Total clottable fibrinogen assays (reference method but time-consuming) 2
  • Clotting rate assays (routine method of choice for bleeding disorders) 2

Management Based on Clinical Context

Active Bleeding

• For patients with active bleeding and fibrinogen <1.5 g/L, administer:

  • Two pools of cryoprecipitate (when available) or fibrinogen concentrate (30-60 mg/kg) 1
  • Fresh frozen plasma (FFP) at 15-30 mL/kg with clinical monitoring for dose adjustments 1
  • For inadequate response to FFP, consider fibrinogen concentrate which provides more rapid and predictable replacement 1

• Monitor fibrinogen levels frequently during bleeding episodes to guide replacement therapy 1

Massive Hemorrhage

• In massive hemorrhage with microvascular oozing or coagulation tests showing fibrinogen <1 g/L:
  • Administer FFP in doses of at least 30 mL/kg 1
  • Add fibrinogen concentrate (30-60 mg/kg) or cryoprecipitate if fibrinogen remains low 1
  • Consider tranexamic acid to prevent hyperfibrinolysis 1, 3

Disseminated Intravascular Coagulation (DIC)

• For DIC-associated hypofibrinogenemia:
  • Treat the underlying cause (e.g., malignancy) as the primary goal 1
  • Administer platelets to maintain count >50 × 10^9/L in actively bleeding patients 1
  • Provide FFP (15-30 mL/kg) with careful monitoring 1
  • Add cryoprecipitate or fibrinogen concentrate for persistent fibrinogen <1.5 g/L 1
  • Consider heparin prophylaxis in highly prothrombotic forms of DIC, avoiding in hyperfibrinolytic DIC 1

Pregnancy and Delivery

• For pregnant women with congenital fibrinogen disorders:
  • Maintain fibrinogen levels ≥1 g/L throughout pregnancy to prevent placental abruption 1
  • Target fibrinogen levels ≥1.5 g/L during labor and delivery 1
  • For cesarean section, maintain fibrinogen levels ≥1.5 g/L 1
  • Monitor postpartum fibrinogen levels targeting ≥1.5 g/L for 3 days after vaginal delivery and 5 days after cesarean section 1
  • Consider tranexamic acid to prevent secondary postpartum hemorrhage 1

Replacement Options

• Fibrinogen concentrate:

  • Advantages: rapid administration, no thawing required, pathogen-inactivated, precise dosing 1, 4
  • Dosing: 30-60 mg/kg 1

• Cryoprecipitate:

  • Contains fibrinogen and other coagulation factors 4
  • Two pools typically used for replacement 1
  • May have delays due to thawing and transportation 1

• Fresh frozen plasma (FFP):

  • Initial dose 15-30 mL/kg, may require larger volumes (≥30 mL/kg) in severe cases 1
  • Less concentrated source of fibrinogen than cryoprecipitate or fibrinogen concentrate 1

Special Considerations

• For patients with liver disease, expect more rapid development of coagulopathy due to decreased production of fibrinogen 1

• Consider thromboprophylaxis in patients receiving fibrinogen replacement who have additional thrombotic risk factors 1

• In patients with both bleeding and thrombotic phenotypes, carefully balance fibrinogen replacement with appropriate thromboprophylaxis 1

• Tranexamic acid can be used as an adjunct therapy to stabilize fibrin and prevent hyperfibrinolysis 1, 3

Monitoring Response

• Repeat fibrinogen levels after replacement therapy to ensure adequate correction 1

• Be aware that the lifespan of transfused fibrinogen may be very short in patients with vigorous coagulation activation and fibrinolysis 1

• Monitor for signs of thrombosis, particularly in patients receiving high doses of fibrinogen replacement 1

Pitfalls to Avoid

• Delaying fibrinogen replacement in actively bleeding patients; early intervention is critical 1

• Using standard FFP doses (15 mL/kg) in massive hemorrhage, which are often inadequate; higher doses (≥30 mL/kg) may be needed 1

• Failing to treat the underlying cause of acquired hypofibrinogenemia (e.g., DIC, liver disease) 1

• Not considering the risk of thrombosis when administering fibrinogen products, especially in patients with a history of thrombotic events 1