When addressing bleeding in patients with CFD, fibrinogen replacement therapy is the cornerstone of care.1 Three options are available: fibrinogen concentrate, cryoprecipitate, and fresh frozen plasma (FFP).1

Fibrinogen concentrate

Advantages

  • Provides a predictable and rapid increase in plasma fibrinogen1
  • Low content of other procoagulant factors1
  • Small reconstitution volume reduces risk of circulatory overload1
  • Streamlined administration fits intraoperative and emergency workflows1
  • Undergoes extensive viral clearance processes2

Limitations

  • High acquisition cost3

  • Limited access due to financial constraints or availability3

  • Not indicated for dysfibrinogenemia4

  • Risk of hypersensitive reactions1

Cryoprecipitate and FFP

Advantages

  • Familiarity with and comfort of use3
  • Hemostatic benefits of VWF, Factor XIII, and fibronectin3
  • FFP contains calibrated content per each 300 mL unit1

Limitations

  • Requires thawing, which can impact time to infusion2
  • Variable fibrinogen content per unit makes dosing less predictable1
  • Risk of transfusion-related complications and larger infusion volumes, increasing the risk of volume overload1
  • Pathogen transmission risks associated with its administration5
  • May contain varying fibrinogen levels5

Recommended fibrinogen levels

ACUTE BLEEDING1

  • Target a peak fibrinogen activity of ≥150 mg/dL in patients with afibrinogenemia or severe hypofibrinogenemia (fibrinogen <50 mg/dL)
  • After achieving hemostasis, maintain a minimum fibrinogen level of 100 mg/dL until complete hemostasis and ≥50 mg/dL throughout wound healing

SURGERY1

  • For minor and major surgery,* fibrinogen supplementation aiming for peak fibrinogen activity >150 mg/dL
  • Subsequent dosing is based on clinical evolution, aiming for a trough fibrinogen activity between 50 mg/dL and 100 mg/dL until wound healing

PREGNANCY1

For moderate and mild hypofibrinogenemia with bleeding phenotype at delivery, fibrinogen supplementation aiming for peak fibrinogen activity >150 mg/dL in women with bleeding phenotype

*Major surgery is defined as most orthopedic, abdominal, gynecologic, urologic, neurologic, thoracic, vascular, gastrointestinal, and otolaryngologic procedures. All other surgical procedures, including dental extractions, are considered minor.1

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References

  1. Casini A. How I treat quantitative fibrinogen disorders. Blood. 2025;145(8):801-810.
  2. Grottke O, Mallaiah S, Karkouti K, Saner F, Haas T. Fibrinogen supplementation and its indications. Semin Thromb Hemost. 2020;46(1):38-49.
  3. Hensley NB, Mazzeffi MA. Pro con debate: fibrinogen concentrate or cryoprecipitate for treatment of acquired hypofibrinogenemia in cardiac surgical patients. Anesth Analg. 2021;133(1):19-28. 
  4. May JE, Wolberg AS, Lim MY. Disorders of fibrinogen and fibrinolysis. Hematol Oncol Clin North Am. 2021;35(6):1197-1217.
  5. Stanford S, Roy A, Cecil T, et al. Differences in coagulation relevant parameters: comparing cryoprecipitate and a human fibrinogen concentrate. PLoS One. 2023;18(8):e0290571.