National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Afibrinogenemia


Other Names:
Afibrinogenemia congenital; Congenital afibrinogenemia
Categories:
Afibrinogenemia, sometimes called congenital afibrinogenemia, is an inherited blood disorder in which the blood does not clot normally. It occurs when there is a lack (deficiency) of a protein called fibrinogen (or coagulation factor I), which is needed for the blood to clot.[1][2] Affected individuals may be susceptible to severe bleeding (hemorrhaging) episodes, particularly during infancy and childhood. Afibrinogenemia is thought to be transmitted as an autosomal recessive trait.[2] Treatment may include cryoprecipitate (a blood product containing concentrated fibrinogen and other clotting factors), fibrinogen (RiaSTAP) or plasma (the liquid portion of the blood which contains clotting factors).[1]

 

Last updated: 5/30/2016

In afibrinogenemia, with fibrinogen levels less than 0.1 g/L, bleeding abnormalities range from mild to severe. Bleeding from the umbilical cord just after birth frequently provides an early alert to the abnormality. Other symptoms include the following:[1][3]

Last updated: 5/30/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 10 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Epistaxis
Bloody nose
Frequent nosebleeds
Nose bleed
Nose bleeding
Nosebleed
[ more ] 		0000421
Gingival bleeding
Bleeding gums
0000225
Joint swelling 0001386
Menometrorrhagia 0400008
Spontaneous abortion 0005268
5%-29% of people have these symptoms
Cerebral hemorrhage
Bleeding in brain
0001342
Percent of people who have these symptoms is not available through HPO
Abnormal bleeding
Bleeding tendency
0001892
Autosomal recessive inheritance 0000007
Hypofibrinogenemia 0011900
Splenic rupture
Ruptured spleen
0012223
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Last updated: 7/1/2020
Afibrinogenemia is caused by a severe lack of fibrinogen (coagulation factor I), a protein in the blood that is essential in the blood clotting (coagulation) process.[1][2][3] This defect in fibrinogen synthesis can result from mutations in one or another of the fibrinogen genes alpha (FGA), beta (FGB) or gamma (FGG).[3][4] Each of these three genes provides instructions for making one part (subunit) of the fibrinogen protein. When an injury occurs, fibrinogen is converted to fibrin, the main protein in blood clots. Fibrin proteins attach to each other, forming a stable network that makes up the blood clot. If there is a mutation in the FGA, FGB or FGG gene, the respective subunit is not made and the fibrinogen protein cannot be assembled. This results in the absence of fibrin, so blood clots cannot form, leading to the excessive bleeding seen in people with afibrinogenemia.[5]
Last updated: 5/30/2016
Afibrinogenemia is inherited in an autosomal recessive manner, meaning that in order to be affected, an individual must have inherited two abnormal genes, one from each parent.[1][2][3][5] The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene. Individuals with just one mutated gene are called carriers and have about half of the normal level of fibrinogen in their blood. They typically don't show signs or symptoms of the condition.[5] When 2 carriers of an autosomal recessive condition have children, each child has a:
  • 25% (1 in 4) chance to be affected,
  • 50% (1 in 2) chance to be an unaffected carrier like each parent,
  • 25% (1 in 4) chance to be unaffected and not be a carrier.
 
Last updated: 5/31/2016

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
There is no known prevention or cure for afibrinogenemia.[1] To treat bleeding episodes or to prepare for surgery to treat other conditions, patients may receive:[1][3]
  • The liquid portion of the blood (plasma)
  • Fibrinogen (RaiSTAP)
  • A blood product containing concentrated fibrinogen (cryoprecipitate) through a vein (transfusion)

Prophylactic therapy should also be considered for patients with recurrent bleeding episodes, CNS hemorrhage, or during pregnancy for women with recurrent miscarriage.[3]

Individuals with afibrinogenemia should consider the following as part of their management plan:

  • Consultation with a hematologist/hemostasis specialist, particularly for patients who require fibrinogen replacement therapy.[3]
  • Genetic counseling and family studies, especially for individuals with extensive family history or those considering pregnancy.[3]
  • Follow-up by a comprehensive bleeding disorder care team experienced in diagnosing and managing inherited bleeding disorders.[3]
  • Vaccination with the hepatitis B vaccine because transfusion increases the risk of hepatitis.[1]


Last updated: 5/31/2016
Although we were not able to find data regarding the life expectancy for individuals with afibrinogenemia, excessive bleeding is common with this condition. These episodes may be severe, or even fatal.[1] Bleeding in the brain is a leading cause of death in patients with this disorder.[1][3] Postoperative bleeding is also commonly associated with mortality in this condition.[3]

Last updated: 5/31/2016
Afibrinogenemia occurs in approximately 1 in 1 million people.[3][5][6] Abolghasemi and Shahverdi (2015) mention that there have been about 250 cases of afibrinogenemia reported in the world literature.[7] You can access general information about the frequency of inherited fibrinogen disorders and other rare bleeding disorders through the Rare Coagulation Disorders Resource Room.
Last updated: 5/31/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Afibrinogenemia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Afibrinogenemia. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Afibrinogenemia. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • How rare is this condition, How many cases are in the USA? See answer

  • I would like to know more about this medical condition. For instance, if I have this condition, can I pass it along to my children? What are the chances of this happening? Can this condition be cured? If not, can it at least be treated? What is the average lifespan of a person with afibrinogenemia? Do women with this condition have complications during pregnancy? Is it safe for them to bear children? See answer


  1. Chen YB, Zieve D. Congenital afibrinogenemia. MedlinePlus. January 27, 2015; http://www.nlm.nih.gov/medlineplus/ency/article/001313.htm.
  2. Afibrinogenemia, Congenital. National Organization for Rare Disorders (NORD). 2007; http://rarediseases.org/rare-diseases/afibrinogenemia-congenital/.
  3. Acharya SS. Inherited Abnormalities of Fibrinogen. Medscape Reference. November 18, 2014; http://emedicine.medscape.com/article/960677-overview.
  4. Afibrinogenemia, Congenital. Online Mendelian Inheritance in Man (OMIM). September 22, 2014; http://omim.org/entry/202400.
  5. Congenital afibrinogenemia. Genetics Home Reference (GHR). September 2014; https://ghr.nlm.nih.gov/condition/congenital-afibrinogenemia.
  6. Familial afibrinogenemia. Orphanet. October 2009; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=98880.
  7. Abolghasemi H, Shahverdi E. Umbilical bleeding: a presenting feature for congenital afibrinogenemia.. Blood Coagul Fibrinolysis. 2015 Oct; 26(7):834-5. https://www.ncbi.nlm.nih.gov/pubmed/26407137.