Familial hypodysfibrinogenemia

Familial hypodysfibrinogenemia is a rare inherited disorder of fibrinogen, the blood clotting protein produced by the liver that plays a central role in the coagulation cascade. This condition represents a combined quantitative and qualitative fibrinogen defect — patients have both reduced levels of fibrinogen in the blood (hypofibrinogenemia) and a fibrinogen molecule that does not function properly (dysfibrinogenemia). It is caused by heterozygous or compound heterozygous mutations in the fibrinogen genes (FGA, FGB, or FGG), resulting in decreased production and/or secretion of an abnormally functioning fibrinogen protein. The clinical presentation of familial hypodysfibrinogenemia is variable. Some individuals may be asymptomatic, while others experience bleeding symptoms ranging from mild to moderate, including easy bruising, prolonged bleeding after surgery or trauma, mucosal bleeding, menorrhagia, and, in some cases, postpartum hemorrhage. Paradoxically, some patients may also be at risk for thrombotic events (abnormal blood clot formation), reflecting the complex role that dysfunctional fibrinogen can play in both bleeding and clotting pathways. The hemostatic system — encompassing blood vessels, platelets, and coagulation factors — is the primary body system affected. Diagnosis is typically established through coagulation studies showing discrepant results between functional (Clauss method) and immunological fibrinogen assays, along with reduced overall fibrinogen antigen levels. Genetic testing of the fibrinogen genes can confirm the diagnosis. Treatment is guided by clinical symptoms and may include fibrinogen replacement therapy (fibrinogen concentrate or cryoprecipitate) for significant bleeding episodes or as prophylaxis before surgical procedures. Antithrombotic therapy may be considered in patients with thrombotic complications. Long-term management requires individualized care with regular monitoring by a hematologist experienced in coagulation disorders.

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