What are the other Names for this Condition? (Also known as/Synonyms)
- Congenital Hypofibrinogenemia
- Familial Afibrinogenemia
What is Congenital Afibrinogenemia? (Definition/Background Information)
- Congenital Afibrinogenemia is a very rare, genetic disorder that causes abnormal excessive bleeding. It is inherited in an autosomal recessive manner
- Normally, the protein fibrinogen is one of the proteins that allows for blood to clot following an injury. The formed blood clot closes (seals) the damaged blood vessels and prevents further blood loss. Individuals with Congenital Afibrinogenemia lack this protein, leading to excessive blood loss
- Babies with this condition are most commonly present with abnormal umbilical cord bleeding at birth. Other signs and symptoms may also include bleeding into the skin, gums, tongue, joints, nosebleeds, gastrointestinal tract (blood in the stools and vomit), or central nervous system bleeding
- Treatment options are available, but they cannot bring about a cure; rather, they help replace the absent fibrinogen. The prognosis of Congenital Afibrinogenemia is usually favorable, if the bleeding episodes are treated promptly. These individuals may have a fatal bleed, if the condition is left untreated
Who gets Congenital Afibrinogenemia? (Age and Sex Distribution)
- Congenital Afibrinogenemia is a genetic condition that is present at birth. The symptoms are usually diagnosed at birth
- The condition is very rare with a prevalence of 1 in 1,000,000. To date, only 150 cases have been documented
- Both males and females have an equal likelihood of inheriting the disorder from their parents
- Since Congenital Afibrinogenemia is an autosomal recessive disorder, there is a higher incidence of this condition in regions or among ethnicities, where consanguineous (closely blood-related) partners or marriages are common
What are the Risk Factors for Congenital Afibrinogenemia? (Predisposing Factors)
The risk factors of Congenital Afibrinogenemia include:
- A positive family history increases one's chances of this condition. Congenital Afibrinogenemia is inherited as an autosomal recessive disorder
It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones 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 Congenital Afibrinogenemia? (Etiology)
Congenital Afibrinogenemia is caused by mutations of the FGA, FGB, or FGG gene. Each gene codes for one part of the multi-part fibrinogen protein. If there is a mutation even in one of the genes, then fibrinogen will not be synthesized correctly, causing abnormalities during blood clot formation, resulting in abnormal bleeding.
- If both parents have the mutated gene (FGA, FGB, or FGG) then the child may develop the disorder. This genetic disorder is inherited in an autosomal recessive pattern, meaning that both parents have to pass on the mutated genes to their offspring, for them to get this condition
- If the child inherits only one copy of the mutated gene, then he/she becomes a carrier, and will not develop Congenital Afibrinogenemia. In such cases, they will only have half of the normal levels of fibrinogen. Milder disease forms are seen if the child inherits only one gene from the parent. These individuals may have abnormal bleeding only during major trauma or high-risk surgical procedures
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).
Note: In Congenital Hypofibrinogenemia, the fibrinogen levels are reduced and far less severe than Congenital Afibrinogenemia.
What are the Signs and Symptoms of Congenital Afibrinogenemia?
The signs and symptoms of Congenital Afibrinogenemia include:
- Bleeding can occur spontaneously or after trivial trauma
- Bleeding from the umbilical cord during birth
- Bleeding in the joints, from the gums or tongue
- Excessive bleeding after injury, bruising
- Blood in stools and vomit (gastrointestinal bleeding)
- Prolonged menstrual bleeding
- Inability to carry pregnancy to a full-term (spontaneous abortion)
How is Congenital Afibrinogenemia Diagnosed?
The following procedures may be used to diagnose Congenital Afibrinogenemia:
- Thorough evaluation of the individual’s medical (and family) history and a complete physical examination including of the skin, joint, muscle, etc.
- During history-taking the physicians may want to know the following:
- When the symptoms began and whether they are becoming worse
- List of prescription and over-the-counter medications currently being taken
- One’s personal and family history of bleeding disorders, associated illnesses, etc.
- Hematologist consultation is often necessary, as they are the experts in dealing with bleeding disorders
Often, the healthcare provider will perform certain blood tests to help determine the severity of the condition. These tests include:
- Fibrinogen levels are absent or very minimal in Congenital Afibrinogenemia
- All of the following tests are prolonged in Congenital Afibrinogenemia:
- Prothrombin time (PT)
- Activated partial thromboplastin time (aPTT)
- Thrombin time
- Reptilase time
- Bleeding time
- If the above tests are shown to be positive, then genotyping (examination for gene mutation) may also be performed to confirm the diagnosis
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 Congenital Afibrinogenemia?
The complications of Congenital Afibrinogenemia include:
- Bleeding from various mucus membranes, intracranial bleeding, or gastrointestinal bleeding may cause death
- In some cases, individuals have also been shown to develop inhibitors to fibrinogen over a period of time, if they undergo multiple replacement treatment. This complicates future treatment
- Paradoxical clotting (thrombosis) may occur while treating for this condition with fibrinogen replacement
- Likelihood of getting infections, such as hepatitis B, during replacement therapy
- Miscarriages are also common in individuals with Congenital Afibrinogenemia
How is Congenital Afibrinogenemia Treated?
The treatment options of Congenital Afibrinogenemia include:
- Individuals with Congenital Afibrinogenemia are often treated by replacing the missing fibrinogen using cryoprecipitate, plasma-derived fibrinogen concentrate, or fresh frozen plasma
- Replacement is given when there is active acute bleeding just before surgical procedures, or as a preventative measure during pregnancy
- The likelihood of contracting hepatitis is increased with replacement therapy. Hence, it is recommended that these individuals receive hepatitis B vaccination, before receiving fibrinogen replacement
How can Congenital Afibrinogenemia be Prevented?
- Currently, there are no specific methods or guidelines to prevent Congenital Afibrinogenemia, since it is a genetic condition
- Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) 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
- Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
What is the Prognosis of Congenital Afibrinogenemia? (Outcomes/Resolutions)
- Excessive bleeding is common in individuals with Congenital Afibrinogenemia. If bleeding episodes remain untreated, it may result in fatalities
- Bleeding in the brain is the main cause of death in individuals diagnosed with Congenital Afibrinogenemia
- With early detection and appropriate treatment of the condition, bleeding episodes can be controlled and fatal complications potentially avoided
Additional and Relevant Useful Information for Congenital Afibrinogenemia:
- A fibrinogen blood test is performed if there are symptoms suggestive of a coagulation disorder - either bleeding (from body sites, or from bleeding spots on skin, or easy bruising), or formation of blood clots
The following article link will help you understand fibrinogen blood test: