hypofibrinogenemia

Hypofibrinogenemia is a medical condition characterized by abnormally low levels of fibrinogen in the blood. Fibrinogen, a soluble plasma glycoprotein produced by the liver, is converted by thrombin into fibrin, forming a stable clot. Normal plasma fibrinogen levels range roughly from 200 to 400 mg/dL; hypofibrinogenemia is typically defined as a fibrinogen level below 150 mg/dL (1.5 g/L).

Causes include congenital forms due to mutations in FGA, FGB, or FGG genes, often inherited in autosomal patterns; these tend to present with lifelong bleeding tendencies and can vary in severity. Acquired hypofibrinogenemia occurs with liver disease, severe malnutrition, disseminated intravascular coagulation, massive transfusion, obstetric hemorrhage, or consumption of fibrinogen during prolonged bleeding or plasminogen activation. Certain drugs or procedures that induce fibrinolysis can contribute.

Clinical presentation ranges from mild mucocutaneous bleeding to life-threatening hemorrhage, particularly during surgery or childbirth. Laboratory evaluation shows low fibrinogen levels by quantitative assays; functional activity measured by Clauss method is likewise reduced. Coagulation screens (PT, aPTT) may be prolonged, and thrombin time is often prolonged as fibrinogen is required for clot formation. Platelet count is typically normal; D-dimer may be elevated if consumption is ongoing.

Management focuses on preventing and treating bleeding by replacing fibrinogen. Treatment options include fibrinogen concentrates or cryoprecipitate to raise plasma fibrinogen to hemostatic levels; fresh frozen plasma is an alternative when concentrates are unavailable. Dosing is guided by the desired fibrinogen level and clinical context, with monitoring of fibrinogen concentration and coagulation tests. Management of any underlying cause is important, especially in acquired cases.

Prognosis depends on the underlying cause and prompt restoration of fibrinogen in bleeding or perioperative settings. Hypofibrinogenemia is rare, and congenital forms require lifelong management and genetic counseling.