Congenital dysfibrinogenemia is a genetic disorder characterized by structural abnormalities of the fibrinogen that commonly result in alterations in the clotting cascade.
Fibrinogen is produced in the liver with a primary role in the formation of a blood clot. Clotting (coagulation) is necessary to stop bleeding (hemorrhages) in case of injuries.
Fibrinogen, also called coagulation factor I, is a protein present in the blood. Fibrinogen is converted to fibrin, a protein required for blood clotting.
In case of dysfibrinogenemia, the dysfunctional fibrinogen molecule alters the correct formation of fibrin, that it is essential to complete the coagulation process.
Dysfibrinogenemia is a genetic disorder due to mutations in the genes FGA (4q31.3), FGB (4q31.3) or FGG (4q32.1) located in chromosome 4, related to fibrinogen protein.
Transmission of most dysfibrinogenemias is autosomal dominant. It means that just one defective copy of a gene (from the father or the mother) is required to cause the disorder.
Congenital dysfibrinogenemia is a rare disorder with only 400 families reported worldwide.
Many individuals with dysfibrinogenemia are asymptomatic (55%) or have prolonged bleeding (25%) that can be noted with the following symptoms:
Paradoxically, certain patients of dysfibrinogenemia are associated with a thrombotic tendency (25%).
In 2% of the cases, there are prolonged bleeding and thrombosis simultaneously.
The symptoms, in any case, depends on the clinical phenotype.
As dysfibrinogenemia is a qualitative defect, the fibrinogen level in the blood is usually in the normal range.
There is another alternative of the disorder called hypodysfibrinogenemia, where there is a combination of dysfunctional fibrinogen and low fibrinogen concentration in the blood (dysfibrinogenemia + hypofibrinogenemia).
However, because the clotting cascade is not properly functional, the screening tests for prothrombin time (PT) and activated partial thromboplastin time (aPTT) are prolonged. Reptilase time is also prolonged.
The definitive test should denote the discrepancy between functional and immunoreactive fibrinogen (for example, low functional activity level with normal or elevated immunological level).
In most cases, there is no need for treatment.
If prolonged bleeding is common, it may be treated with fibrinogen replacement, especially before surgery or childbirth.
Thrombosis associated with dysfibrinogenemia may require anticoagulation therapy (warfarin or heparin) and long-term prophylaxis.
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