How is fibrinogen deficiency or dysfunction treated?

Treatment of Fibrinogen Deficiency or Dysfunction

Fibrinogen replacement therapy targeting levels ≥1.5 g/L is the cornerstone of treatment for bleeding episodes in patients with congenital or acquired fibrinogen deficiency, with plasma-derived fibrinogen concentrate being the preferred agent over cryoprecipitate or fresh frozen plasma. 1, 2

Treatment Approach by Clinical Scenario

Congenital Fibrinogen Disorders

Acute Bleeding Episodes:

• Administer fibrinogen replacement targeting plasma levels ≥1.5 g/L until bleeding cessation 1
• Fibrinogen concentrate is the agent of choice, with typical dosing of 30-60 mg/kg providing rapid, predictable correction without requiring thawing 1, 2
• Cryoprecipitate or fresh frozen plasma should only be used when fibrinogen concentrate is unavailable 2
• For severe bleeding with fibrinogen <1.0 g/L, doses of at least 4 g of fibrinogen concentrate have shown efficacy in improving coagulation parameters 3

Surgical Management:

• Maintain fibrinogen levels ≥1.5 g/L throughout the perioperative period 1
• For cesarean section or vaginal delivery in patients with bleeding phenotype, target fibrinogen ≥1.5 g/L 1
• Neuraxial anesthesia requires fibrinogen levels ≥1.5 g/L with continuous monitoring throughout the procedure 1

Prophylactic Treatment:

• Secondary prophylaxis may be considered after life-threatening bleeding episodes, targeting fibrinogen activity levels >0.5-1.0 g/L 4
• Primary prophylaxis is not routinely recommended except in specific high-risk situations 2
• Pregnant women with afibrinogenemia require prophylactic replacement as early as possible, continuing throughout pregnancy and postpartum 4

Acquired Fibrinogen Deficiency

Massive Hemorrhage/Trauma:

• Administer FFP at doses of at least 30 ml/kg as first-line response when fibrinogen <1.0 g/L or PT/aPTT >1.5 times normal 1
• Standard doses of FFP 15 ml/kg are often inadequate; anticipate need for higher volumes 1
• Fibrinogen concentrate 30-60 mg/kg provides more rapid and predictable correction than cryoprecipitate, without thawing delays 1, 5
• Maintain platelet count ≥75 × 10⁹/L concurrently 1
• Consider early FFP administration to prevent dilutional coagulopathy when blood loss of one blood volume is anticipated 1

Liver Disease:

• Routine correction of fibrinogen deficiency to decrease procedure-related bleeding is discouraged 1
• Fibrinogen levels <100 mg/dl are associated with spontaneous and procedure-related bleeding, but this may reflect disease severity rather than causation 1
• When replacement is necessary, anticipate that larger volumes of FFP will be required due to dysfunctional fibrinogen production 1

Special Populations

Pregnancy Management

Dysfibrinogenemia:

• Fibrinogen replacement is not routinely recommended during pregnancy 1
• For vaginal bleeding during pregnancy, institute replacement targeting ≥1.5 g/L until bleeding stops 1
• Quarterly assessment of fibrinogen activity and antigen levels is recommended 1
• For dysfibrinogenemia type 3B (thrombotic variants), initiate thromboprophylaxis at pregnancy confirmation and continue for 6 weeks postpartum 1

Postpartum Management:

• Close clinical monitoring for 72 hours in patients with bleeding phenotype 1
• Early use of fibrinogen replacement and tranexamic acid for postpartum bleeding, targeting levels >1.5 g/L 1

Dysfibrinogenemia with Thrombotic Risk

• Avoid excessive fibrinogen replacement in patients with thrombotic phenotypes 6
• For dysfibrinogenemia type 3B, thromboprophylaxis takes precedence over fibrinogen replacement 1, 6
• Target fibrinogen levels should not exceed necessary therapeutic thresholds to minimize thrombotic complications 6

Critical Thresholds

• <1.0 g/L: Critical level requiring immediate replacement in bleeding patients 1, 5
• ≥1.5 g/L: Target for active bleeding, surgery, neuraxial anesthesia, and delivery 1
• >2.0 g/L: May improve hemostasis further in massive hemorrhage, but avoid excessive elevation in thrombotic-risk patients 1, 6

Common Pitfalls

• Underdosing fibrinogen replacement: Standard FFP doses of 15 ml/kg are frequently inadequate for active bleeding; use at least 30 ml/kg 1
• Delays with cryoprecipitate: Thawing and preparation time can be critical; fibrinogen concentrate provides immediate availability 1, 5
• Over-replacement in thrombotic phenotypes: Excessive fibrinogen elevation increases thrombotic risk, particularly in dysfibrinogenemia type 3B 6
• Ignoring platelet count: Fibrinogen replacement alone is insufficient; maintain platelets ≥75 × 10⁹/L in massive hemorrhage 1
• Routine correction in liver disease: Prophylactic fibrinogen correction for procedures in cirrhosis is not supported by evidence and should be avoided 1