Afibrinogenemia

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. This defect in fibrinogen synthesis can result from mutations in one or another of the fibrinogen genes alpha ( FGA), beta ( FGB) or gamma ( FGG). 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.

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. 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. 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.

Aside from the fact that women have similar symptoms to men with bleeding disorders (recurrent nosebleeds, easy bruising, bleeding from the digestive or urinary tract and excessive bleeding from the mouth or gums), they can also experience added obstetric and gynecological complications. Bleeding disorders are particularly troublesome for reproductive-aged women. Heavy and prolonged menstrual bleeding, also known as menorrhagia, can lead to serious complications if left untreated.

Recurrent spontaneous abortions can also occur in women with afibrinogenemia. This phenomenon, however, may be prevented by routine prophylaxis with fibrinogen concentrates starting early in pregnancy. In addition, women with afibrinogenemia may experience postpartum hemorrhage.

In cases where a woman with a bleeding disorder becomes pregnant, it is recommended that she see an obstetrician as soon as possible. This will help ensure that the doctor can consult with the appropriate specialists who can provide pre- and postnatal care for the woman and her baby.

To find a specialist in your area, click here or contact the National Hemophilia Foundation's Information Resource Center, HANDI, at 1-800-424-2634 or handi@hemophilia.org.

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. 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. 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).

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. Bleeding in the brain is a leading cause of death in patients with this disorder. Postoperative bleeding is also commonly associated with mortality in this condition.

Afibrinogenemia occurs in approximately 1 in 1 million people. Abolghasemi and Shahverdi (2015) mention that there have been about 250 cases of afibrinogenemia reported in the world literature. You can access general information about the frequency of inherited fibrinogen disorders and other rare bleeding disorders through the Rare Coagulation Disorders Resource Room.

There is no known prevention or cure for afibrinogenemia. To treat bleeding episodes or to prepare for surgery to treat other conditions, patients may receive:

• 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.

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.
• Genetic counseling and family studies, especially for individuals with extensive family history or those considering pregnancy.
• Follow-up by a comprehensive bleeding disorder care team experienced in diagnosing and managing inherited bleeding disorders.
• Vaccination with the hepatitis B vaccine because transfusion increases the risk of hepatitis.