Afibrinogenemia

Alternate names

Afibrinogenemia congenital; Congenital afibrinogenemia

Definition

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.

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Normally, blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss. However, bleeding is uncontrolled in people with congenital afibrinogenemia. Newborns with this condition often experience prolonged bleeding from the umbilical cord stump after birth.

Epidemiology

Congenital afibrinogenemia is a rare condition that occurs in approximately 1 in 1 million newborns.

Cause

• Congenital afibrinogenemia results from mutations in one of three genes, FGA, FGB, or FGG.
• Each of these genes provides instructions for making one part (subunit) of a protein called fibrinogen.
• This protein is important for blood clot formation (coagulation), which is needed to stop excessive bleeding after injury.
• In response to injury, 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.

Gene mutations

• Congenital afibrinogenemia is caused by a complete absence of fibrinogen protein.
• Most FGA, FGB, and FGG gene mutations that cause this condition result in a premature stop signal in the instructions for making the respective protein.
• If any protein is made, it is nonfunctional.
• When any one subunit is missing, the fibrinogen protein is not assembled, which results in the absence of fibrin.
• Consequently, blood clots do not form in response to injury, leading to the excessive bleeding seen in people with congenital afibrinogenemia.

Inheritance

Autosomal recessive inheritance, a 25% chance

Congenital afibrinogenemia is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene. The parents have about half the normal level of fibrinogen in their blood but typically do not show signs and symptoms of the condition.

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:

• 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

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Epistaxis(Bloody nose)
• Gingival bleeding(Bleeding gums)
• Joint swelling
• Menometrorrhagia
• Spontaneous abortion

5%-29% of people have these symptoms

• Cerebral hemorrhage(Bleeding in brain)

Diagnosis

If your health care provider suspects this problem, you will have lab tests to confirm the type and severity of the disorder.

Tests include:

• Bleeding time
• Fibrinogen test and reptilase time to check fibrin level and quality
• Partial thromboplastin time (PTT)
• Prothrombin time (PT)
• Thrombin time

Treatment

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.

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. 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.

Vaccination with the hepatitis B vaccine because transfusion increases the risk of hepatitis.

NIH genetic and rare disease info

• NIH info on Afibrinogenemia

Afibrinogenemia is a rare disease.

Afibrinogenemia Resources
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