What are the other Names for this Condition? (Also known as/Synonyms)

• Acquired Dysfibrinogenemia
• Congenital Dysfibrinogenemia
• Familial Dysfibrinogenemia

What is Dysfibrinogenemia? (Definition/Background Information)

• Dysfibrinogenemia is a coagulation (clotting) disorder characterized by having an abnormal form of fibrinogen
  • Fibrinogen is a protein produced by the liver, which helps control bleeding by helping blood clots to form
  • Having abnormal fibrinogen results in defective clot formation and can cause an increased or decreased ability to clot
• Dysfibrinogenemias may be inherited (congenital) or acquired
  • Congenital Dysfibrinogenemia is rare. About 40% of people with this form have no symptoms. About 50% have a bleeding disorder, and the remaining 10% have either a thrombotic disorder (excessive clotting) or both bleeding and thrombotic disorders
  • Acquired Dysfibrinogenemia is more common than the congenital form and is associated with liver disease such as cirrhosis, liver tumors, or hepatitis
• Congenital Dysfibrinogenemias may be caused by mutations in the FGA, FGB or FGG genes
• Inheritance is most often autosomal dominant or codominant, but can also be autosomal recessive
• Whether a person has no symptoms, a bleeding tendency, or an increased risk of thrombosis depends on the effect of their specific mutation(s)
• Most people with Dysfibrinogenemia have no symptoms and don't need treatment. For the remainder, treatment is individualized and depends on the symptoms and severity in each person

(Source: Dysfibrinogenemia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Dysfibrinogenemia? (Age and Sex Distribution)

• Dysfibrinogenemia is a rare disorder, which can be inherited or acquired
• Congenital Dysfibrinogenemia is considered rare, but the true incidence is unknown since many forms do not cause signs or symptoms. In the literature, only 200-300 families have been reported
• Approximately 50% of patients with severe liver disease have bleeding tendencies secondary to abnormal fibrinogen (acquired Dysfibrinogenemia)

(Source: Dysfibrinogenemia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Dysfibrinogenemia? (Predisposing Factors)

The risk factors for Dysfibrinogenemia include:

• A positive family history of the disorder
• Having liver diseases, such as, cirrhosis, hepatitis or tumors/cancers of the liver

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Dysfibrinogenemia? (Etiology)

Dysfibrinogenemia is caused by abnormalities in fibrinogen.

• Having abnormal fibrinogen results in defective clot formation and can cause an increased or decreased ability to clot
• Fibrinogen is a protein produced by the liver, which helps control bleeding by helping blood clots to form
• Dysfibrinogenemia can either be inherited or acquired. Acquired Dysfibrinogenemia is more common than the congenital form and is associated with liver disease such as cirrhosis, liver tumors, or hepatitis
• The inherited form is caused by mutation(s) in the FGA, FGB or FGG genes
• Inheritance is most often autosomal dominant or codominant, but can also be autosomal recessive

(Source: Dysfibrinogenemia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Autosomal co-dominant: In this type of inheritance, an individual inherits a copy of a causative gene mutation from each parent. Both copies (alleles) of the causative gene influence occurrence and progression of disease.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Dysfibrinogenemia?

The signs and symptoms of Dysfibrinogenemia may vary, depending on the gene affected, and if the mutation causes increased or decreased clotting. Whereas some affected individuals may be asymptomatic, other may exhibit the following signs and symptoms of Dysfibrinogenemia 

Very frequently present symptoms in 80-99% of the cases:

• Epistaxis (nose bleeding)
• Gastrointestinal hemorrhage
• Gingival bleeding

Frequently present symptoms in 30-79% of the cases: Venous thrombosis

(Source: Dysfibrinogenemia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

If Dysfibrinogenemia develops as a consequence of liver disease, then additional symptoms pertaining to the causative disease may be present.

How is Dysfibrinogenemia Diagnosed?

Dysfibrinogenemia is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Dysfibrinogenemia?

The complications of Dysfibrinogenemia may include:

• Bleeding from various mucus membranes, intracranial bleeding, or gastrointestinal bleeding may cause death
• Greater likelihood of infections
• Miscarriages

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Dysfibrinogenemia Treated?

• There is no cure for inherited Dysfibrinogenemia, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops
• For acquired Dysfibrinogenemia, treatment is given for the pre-existing condition causing Dysfibrinogenemia. In case of thrombosis, heparin with subsequent oral anti-coagulants may be necessary

How can Dysfibrinogenemia be Prevented?

• Currently, Dysfibrinogenemia may not be preventable, if it is a genetic disorder
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Seeking prompt medical attention for serious liver diseases may help minimize the occurrence of Dysfibrinogenemia
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Dysfibrinogenemia? (Outcomes/Resolutions)  

• The prognosis of Dysfibrinogenemia is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Dysfibrinogenemia:

• Dysfibrinogenemia is also known by the following names: Inherited Dysfibrinogenemia

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/