Afibrinogenemia

Title

Other Names:

Afibrinogenemia congenital; Congenital afibrinogenemia

Categories:

Blood Diseases; Congenital and Genetic Diseases

Summary Summary

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

Symptoms Symptoms

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]

Nosebleeds that are difficult to stop
Bleeding in the mucus membranes
Bleeding in the joints
Bruising easily
Gastrointestinal bleeding
Menorrhagia and postpartum hemorrhage
Heavy bleeding after injury or surgery
Spontaneous rupture of the spleen
Bleeding inside the skull (intracranial hemorrhage) - very rare
Miscarriage

Last updated: 5/30/2016

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Epistaxis	Very frequent (present in 80%-99% of cases)
Gingival bleeding	Very frequent (present in 80%-99% of cases)
Joint swelling	Very frequent (present in 80%-99% of cases)
Menometrorrhagia	Very frequent (present in 80%-99% of cases)
Spontaneous abortion	Very frequent (present in 80%-99% of cases)
Cerebral hemorrhage	Occasional (present in 5%-29% of cases)
Abnormal bleeding	-
Autosomal recessive inheritance	-
Hypofibrinogenemia	-
Splenic rupture	-

Last updated: 9/1/2017

Cause Cause

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

Inheritance Inheritance

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

Diagnosis Diagnosis

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.

Treatment Treatment

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

Prognosis Prognosis

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

Statistics Statistics

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

Do you have updated information on this condition? Let us know.

Research Research

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 studying or have studied 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.

Organizations Organizations

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

National Hemophilia Foundation
7 Penn Plaza, Suite 1204
New York, NY 10001
Toll-free: 800-42-HANDI
Telephone: 212-328-3700
Fax: 212-328-3799
E-mail: handi@hemophilia.org
Website: http://www.hemophilia.org/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

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.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

GARD Answers GARD Answers

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

Have a question? Contact a GARD Information Specialist.

References References

Chen YB, Zieve D. Congenital afibrinogenemia. MedlinePlus. January 27, 2015; http://www.nlm.nih.gov/medlineplus/ency/article/001313.htm.
Afibrinogenemia, Congenital. National Organization for Rare Disorders (NORD). 2007; http://rarediseases.org/rare-diseases/afibrinogenemia-congenital/.
Acharya SS. Inherited Abnormalities of Fibrinogen. Medscape Reference. November 18, 2014; http://emedicine.medscape.com/article/960677-overview.
Afibrinogenemia, Congenital. Online Mendelian Inheritance in Man (OMIM). September 22, 2014; http://omim.org/entry/202400.
Congenital afibrinogenemia. Genetics Home Reference (GHR). September 2014; https://ghr.nlm.nih.gov/condition/congenital-afibrinogenemia.
Familial afibrinogenemia. Orphanet. October 2009; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=98880.
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.