How is hypofibrinogenemia treated?

Treatment of Hypofibrinogenemia

Hypofibrinogenemia should be treated with fibrinogen concentrate (3-4 g initial dose) or cryoprecipitate (15-20 single donor units) when fibrinogen levels fall below 1.5 g/L in the setting of major bleeding, with fibrinogen concentrate offering more rapid and predictable correction. 1

Treatment Thresholds and Initial Dosing

Initiate fibrinogen replacement when:

• Plasma Clauss fibrinogen level ≤ 1.5 g/L with major bleeding 1
• Fibrinogen < 1.0 g/L with widespread microvascular oozing 1
• Viscoelastic testing (ROTEM/TEG) shows functional fibrinogen deficit 1

Initial dosing:

• Fibrinogen concentrate: 3-4 g (or 50 mg/kg) - this is the preferred first-line dose 1, 2
• Cryoprecipitate: 15-20 single donor units (equivalent fibrinogen content) 1
• Each gram of fibrinogen concentrate increases plasma fibrinogen by 0.2-0.3 g/L 1

Choice Between Fibrinogen Concentrate vs Cryoprecipitate

Fibrinogen concentrate is preferred when available because:

• No thawing required - achieves more rapid correction 1
• More predictable fibrinogen content and dosing 1
• Viral inactivation provides enhanced safety 3
• Concentrated formulation (20 g/L after reconstitution) 1

Cryoprecipitate advantages:

• Contains additional factors (von Willebrand factor, Factor VIII, Factor XIII) 1
• May provide broader hemostatic support in some contexts 1
• More widely available in some regions 1

The 2023 European trauma guidelines acknowledge that despite limited high-quality RCT evidence, both products are recommended for hypofibrinogenemia with major bleeding 1. A systematic review found no difference in mortality or transfusion requirements between the two, though evidence quality remains low 1.

Administration Guidelines

Fibrinogen concentrate administration rates: 2

• Acquired deficiency: maximum 20 mL per minute
• Congenital deficiency: maximum 5 mL per minute

Do not administer additional fibrinogen if plasma concentration exceeds 1.5 g/L without ongoing bleeding 2

Monitoring and Repeat Dosing

Guide repeat doses using: 1, 2

• Serial Clauss fibrinogen measurements (target ≥ 1.5 g/L)
• Viscoelastic monitoring (ROTEM/TEG) for functional assessment
• Clinical assessment of bleeding control

In massive hemorrhage contexts:

• Fresh frozen plasma (FFP) at 30 ml/kg may be needed as first-line when fibrinogen products unavailable 1
• Standard FFP doses (15 ml/kg) are inadequate for established coagulopathy 1
• Maintain platelet count ≥ 75 × 10⁹/L concurrently 1

Special Population: Pregnancy

For congenital fibrinogen disorders in pregnancy: 4, 2

• Maintain trough fibrinogen ≥ 1.0 g/L throughout pregnancy to prevent placental abruption
• Target ≥ 1.5 g/L for labor and delivery
• Monitor weekly initially, then monthly after stabilization

In obstetric hemorrhage (e.g., placental abruption): 4

• Fibrinogen < 200 mg/dL predicts severe postpartum hemorrhage
• Consider ROTEM/TEG for rapid functional assessment

Adjunctive Measures

Tranexamic acid should be administered when hyperfibrinolysis is anticipated or confirmed 1, as it enhances fibrinogen efficacy and reduces bleeding in trauma and obstetric hemorrhage.

Monitor and correct: 1

• Hypocalcemia (impairs coagulation cascade)
• Hypomagnesemia (affects platelet function)

Safety Considerations

Monitor for thrombotic complications: 2

• Allergic reactions and anaphylaxis are possible
• Avoid excessive fibrinogen replacement (>1.5 g/L without bleeding) 2

Recombinant Factor VIIa is NOT recommended 1 - it carries thrombotic risk and is ineffective with low fibrinogen levels.

Clinical Outcomes

Retrospective studies demonstrate that fibrinogen concentrate achieves normalization of fibrinogen levels more rapidly than FFP 3, 5, with 67% of patients achieving bleeding control within 4 hours 5. The intervention significantly reduces red blood cell and FFP transfusion requirements 3, 5, though high-quality RCT evidence for mortality benefit remains lacking 1, 6.