CFD OVERVIEW

CFD is a rare hereditary condition, thought to represent approximately 8% of rare bleeding disorders worldwide. The condition arises from mutations in FGA, FGB, or FGG, resulting in quantitative or qualitative defects in fibrinogen production.2



Diagnosis is established through a combination of the Clauss functional fibrinogen assay and antigenic fibrinogen levels, enabling clinicians to distinguish between afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia.2 

CLINICAL PRESENTATION

Heterogeneous presentation
CFD presents heterogeneously. Patients may experience easy bruising, epistaxis, heavy menstrual bleeding, postpartum hemorrhage, surgical bleeding, gastrointestinal bleeding, or, in rare cases, life-threatening intracranial hemorrhage.2 



Risk for thrombosis
Despite CFD being fundamentally a bleeding disorder, up to 20% of patients can develop venous or arterial thrombosis due to absent or dysfunctional fibrinogen, abnormal fibrin architecture, and the loss of fibrinogen antithrombin activity.2



 

Obstetric complications
Additionally, obstetric complications are especially notable in women with CFD. In a systematic review, 43% of pregnancies in women with CFD resulted in miscarriage, with significantly elevated rates of placental abruption and postpartum hemorrhage compared with the general population.2

 

CLINICAL EXPERTS' RECOMMENDATIONS SUGGEST FC FOR RAPID FIBRINOGEN REPLACEMENT1

Restoration of fibrinogen concentration leads to improved outcomes3

Management of CFD is guided by the severity and context of bleeding. In acute major hemorrhage, expert consensus recommends achieving specific fibrinogen targets (eg, > 150 mg/dL for intracranial hemorrhage; > 100 mg/dL for hemarthrosis; > 50 mg/dL for all other bleeds) using fibrinogen replacement.2 



 

Fresh frozen plasma (FFP) and cryoprecipitate are options, although they may require larger infusion volumes. Fibrinogen concentrates typically are a rapid, reliable option when available.1,4 When surgical intervention is required, a fibrinogen optimization plan is essential.1

 

 

MANAGEMENT OF EPISODIC ACUTE BLEEDING1


During acute bleeding episodes, 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.

MANAGEMENT OF ACUTE BLEEDING DURING SURGERY1

For patients with afibrinogenemia or severe hypofibrinogenemia undergoing minor or major procedures,* fibrinogen supplementation should aim for a peak fibrinogen activity > 150 mg/dL.
Subsequent dosing is based on clinical evolution and should aim for a trough fibrinogen activity between 50 mg/dL and 100 mg/dL until wound healing.

MANAGEMENT OF ACUTE BLEEDING DURING PREGNANCY1

For moderate and mild hypofibrinogenemia at delivery, fibrinogen supplementation should aim for a 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

FC to treat CFD

THE TARGETED AND RAPID APPROACH FOR TREATING CFD5

NO NEED TO WAIT

FC can be readily available, as it does not need thawing or ABO matching, and can be stored at the POC,3,6 while cryo thawing time can be up to 45 minutes.7

LESS VOLUME & FEWER TRANSFUSIONS

Less volume is needed to correct fibrinogen levels as compared to cryo and FFP1,7

PATHOGEN REDUCED

FC products undergo viral inactivation steps, which can significantly reduce the risk of viral transmission.3,6-8

CONSISTENT DOSING

FC contains a precise amount of fibrinogen, labeled in every vial, allowing for predictable response,6 while fibrinogen content in cryo is variable.7

ESTABLISHED SAFETY

  • Manufactured using pathogen-reduction steps that provide a high degree of viral safety3
  • Produced through a controlled, standardized manufacturing process that includes pasteurization and viral inactivation4,9

CFD: congenital fibrinogen deficiency; cryo: cryoprecipitate; FC: fibrinogen concentrate; POC: point of care.

FIND OUT MORE ABOUT FESILTY

Consider FESILTY as a first-line treatment for CFD

Learn More
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IMPORTANT SAFETY INFORMATION

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Indications and Usage
FESILTY (fibrinogen, human-chmt) is a human blood coagulation factor indicated for the treatment of acute bleeding episodes in pediatric and adult patients with congenital fibrinogen deficiency, including hypo- or afibrinogenemia.


Limitations of Use:
FESILTY is not indicated for dysfibrinogenemia.
 
Contraindications
FESILTY is contraindicated in patients who have severe hypersensitivity reactions, including anaphylaxis, to FESILTY or its components (arginine hydrochloride, polysorbate 80, sodium citrate dihydrate, trehalose dihydrate).
 
Warnings and Precautions
Hypersensitivity reactions have occurred in patients receiving FESILTY. Should symptoms occur, discontinue FESILTY and administer appropriate treatment.
 
Thrombotic events have occurred in patients receiving FESILTY. Weigh the benefits of administration versus the risks of thrombosis.
 
FESILTY is made from pooled human plasma and may carry the risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
 
Adverse Reactions
The most serious adverse reactions observed with FESILTY were thrombotic events, including portal vein thrombosis, deep vein thrombosis, and pain in extremity with clinically suspected thrombosis. One patient had an episode of epilepsy and died due to extradural hematoma 4 weeks after administration of FESILTY.
 
In a clinical study, the most common adverse reactions that occurred in >2% of patients receiving FESILTY were pain in extremity, back pain, hypersensitivity reactions, pyrexia, thrombosis, fibrin D dimer increased, headache, and vomiting.
 
Please see full Prescribing Information for FESILTY.
 
To report SUSPECTED ADVERSE REACTIONS, contact Grifols Therapeutics LLC at 1-800-520-2807 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Indications and Usage
FESILTY (fibrinogen, human-chmt) is a human blood coagulation factor indicated for the treatment of acute bleeding episodes in pediatric and adult patients with congenital fibrinogen deficiency, including hypo- or afibrinogenemia.


Limitations of Use:
FESILTY is not indicated for dysfibrinogenemia.
 
Contraindications
FESILTY is contraindicated in patients who have severe hypersensitivity reactions, including anaphylaxis, to FESILTY or its components (arginine hydrochloride, polysorbate 80, sodium citrate dihydrate, trehalose dihydrate).
 
Warnings and Precautions
Hypersensitivity reactions have occurred in patients receiving FESILTY. Should symptoms occur, discontinue FESILTY and administer appropriate treatment.
 
Thrombotic events have occurred in patients receiving FESILTY. Weigh the benefits of administration versus the risks of thrombosis.
 
FESILTY is made from pooled human plasma and may carry the risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
 
Adverse Reactions
The most serious adverse reactions observed with FESILTY were thrombotic events, including portal vein thrombosis, deep vein thrombosis, and pain in extremity with clinically suspected thrombosis. One patient had an episode of epilepsy and died due to extradural hematoma 4 weeks after administration of FESILTY.
 
In a clinical study, the most common adverse reactions that occurred in >2% of patients receiving FESILTY were pain in extremity, back pain, hypersensitivity reactions, pyrexia, thrombosis, fibrin D dimer increased, headache, and vomiting.
 
Please see full Prescribing Information for FESILTY.
 
To report SUSPECTED ADVERSE REACTIONS, contact Grifols Therapeutics LLC at 1-800-520-2807 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

IMPORTANT SAFETY INFORMATION

Indications and Usage
FESILTY (fibrinogen, human-chmt) is a human blood coagulation factor indicated for the treatment of acute bleeding episodes in pediatric and adult patients with congenital fibrinogen deficiency, including hypo- or afibrinogenemia.


Limitations of Use:
FESILTY is not indicated for dysfibrinogenemia.
 
Contraindications
FESILTY is contraindicated in patients who have severe hypersensitivity reactions, including anaphylaxis, to FESILTY or its components (arginine hydrochloride, polysorbate 80, sodium citrate dihydrate, trehalose dihydrate).
 
Warnings and Precautions
Hypersensitivity reactions have occurred in patients receiving FESILTY. Should symptoms occur, discontinue FESILTY and administer appropriate treatment.
 
Thrombotic events have occurred in patients receiving FESILTY. Weigh the benefits of administration versus the risks of thrombosis.
 
FESILTY is made from pooled human plasma and may carry the risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
 
Adverse Reactions
The most serious adverse reactions observed with FESILTY were thrombotic events, including portal vein thrombosis, deep vein thrombosis, and pain in extremity with clinically suspected thrombosis. One patient had an episode of epilepsy and died due to extradural hematoma 4 weeks after administration of FESILTY.
 
In a clinical study, the most common adverse reactions that occurred in >2% of patients receiving FESILTY were pain in extremity, back pain, hypersensitivity reactions, pyrexia, thrombosis, fibrin D dimer increased, headache, and vomiting.
 
Please see full Prescribing Information for FESILTY.
 
To report SUSPECTED ADVERSE REACTIONS, contact Grifols Therapeutics LLC at 1-800-520-2807 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

  1. Casini How I treat quantitative fibrinogen disorders. Blood. 2025;145(8):801-810. 
  2. May JE, Wolberg AS, Lim MY. Disorders of fibrinogen and fibrinolysis. Hematol Oncol Clin North Am. 2021;35(6):1197-1217. 
  3. Grottke O, Mallaiah S, Karkouti K, Saner F, Haas T. Fibrinogen supplementation and its indications. Semin Thromb Hemost. 2020;46(1):38-49. 
  4. Roy A, Sargant N, Bell J, et al. Comparison of coagulation parameters associated with fibrinogen concentrate and cryoprecipitate for treatment of bleeding in patients undergoing cytoreductive sugery for pseudomyxoma peritonei: subanalysis from a randomized controlled phase 2 study. Health Sci Rep. 2023;6:1-10. 
  5. Manco-Johnson MJ, DiMichele D, Castaman G, et al. Pharmacokinetics and safety of fibrinogen concentrate. J Thromb Haemost. 2009;7:2064-2069.
  6. FESILTY [package insert]. Grifols, S.A.
  7. 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. 
  8. Zirkel F, Luelf S, Asper Scheich C, Poelsler G. UV-C irradiation: virus inactivation in fibrinogen concentrate manufacturing process. Poster presented at: 66th American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, CA. 
  9. Gomes Angelo-Dias Duarte GS, Dias SS, Serra SS, Lima J. Safety of fibrinogen concentrate in non-trauma and non-obstetric adult patients during perioperative care: systemic review and meta-analysis. J Clin Med. 2024;13:1-18.