dysfibrinogenemia

Dysfibrinogenemia is a qualitative fibrinogen disorder in which the fibrinogen molecules present in the blood are structurally abnormal and functionally defective, leading to impaired clot formation despite normal or near-normal fibrinogen antigen levels. The condition can be congenital, usually due to mutations in the FGA, FGB, or FGG genes, and most forms are inherited in an autosomal dominant pattern. Acquired cases occur in association with liver disease, autoimmune disorders, pregnancy-related conditions, or certain medications and illnesses that affect fibrinogen synthesis or function.

Clinically, dysfibrinogenemia shows considerable variability. Some individuals are asymptomatic, while others may experience bleeding symptoms such as mucosal bleeding, easy bruising, or menorrhagia. There is also an associated risk of thrombosis in some patients, including deep vein thrombosis or pulmonary embolism. Pregnancy can complicate the condition, increasing the risk of miscarriage or placental problems in certain cases. Because the condition affects the functional quality of fibrinogen rather than its amount, patients often have normal or near-normal fibrinogen antigen levels.

Diagnosis relies on discordant laboratory results: a functional fibrinogen assay (such as the Clauss method) shows reduced activity, while quantitative antigen measurements may be normal or only mildly reduced. Additional tests, including thrombin time and reptilase time, can be prolonged. Genetic testing can identify specific fibrinogen gene mutations. Management is individualized and depends on symptoms, focusing on treating bleeding with fibrinogen concentrates or cryoprecipitate during procedures or major bleeding, and using anticoagulation for thrombosis when indicated. Regular follow-up and counseling are recommended.