Congenital fibrinogen deficiency

Congenital fibrinogen deficiency (also known as congenital fibrinogen disorder) is a group of rare inherited bleeding disorders caused by mutations in the fibrinogen genes (FGA, FGB, or FGG), which encode the three polypeptide chains of fibrinogen, a key protein in blood clot formation. Fibrinogen (Factor I) is produced by the liver and plays a central role in the final step of the coagulation cascade, where it is converted to fibrin to form a stable blood clot. Congenital fibrinogen deficiency encompasses several subtypes: afibrinogenemia (complete absence of fibrinogen), hypofibrinogenemia (reduced levels of fibrinogen), dysfibrinogenemia (normal levels but abnormal function of fibrinogen), and hypodysfibrinogenemia (both reduced levels and abnormal function). The clinical presentation varies widely depending on the subtype and severity. Afibrinogenemia, the most severe form, typically presents in the neonatal period with umbilical cord bleeding, and affected individuals experience recurrent and potentially life-threatening bleeding episodes including mucocutaneous bleeding, hemarthrosis (joint bleeding), muscle hematomas, gastrointestinal hemorrhage, and intracranial hemorrhage. Women may experience menorrhagia and recurrent pregnancy loss. Paradoxically, some patients—particularly those with dysfibrinogenemia—may also be at risk for thromboembolic events. Hypofibrinogenemia generally causes milder bleeding symptoms, while dysfibrinogenemia can be asymptomatic, associated with bleeding, or associated with thrombosis. Treatment is primarily based on fibrinogen replacement therapy using fibrinogen concentrate (such as human fibrinogen concentrate) or cryoprecipitate to restore adequate fibrinogen levels during bleeding episodes or as prophylaxis before surgical procedures. Long-term prophylactic replacement therapy may be considered for patients with afibrinogenemia who experience frequent or severe bleeding. Antifibrinolytic agents such as tranexamic acid may be used as adjunctive therapy. For patients with thrombotic complications, anticoagulation therapy may be necessary. Genetic counseling is recommended for affected families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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