Afibrinogenaemia

Afibrinogenaemia

Afibrinogenaemia is a rare genetic disorder characterized by the complete absence of fibrinogen, a protein essential for blood clotting. This condition leads to severe bleeding tendencies, as fibrinogen is crucial for the formation of a stable blood clot. Afibrinogenaemia is classified as a type of congenital fibrinogen disorder.

Pathophysiology

Fibrinogen, also known as Factor I, is a glycoprotein that is synthesized in the liver and circulates in the blood plasma. It plays a critical role in hemostasis, the process that stops bleeding at the site of an injury. In individuals with afibrinogenaemia, mutations in the genes responsible for fibrinogen production (FGA, FGB, and FGG) lead to the absence of this protein in the blood.

Without fibrinogen, the blood clotting cascade is disrupted. Normally, fibrinogen is converted to fibrin by the action of thrombin, forming a mesh that stabilizes the platelet plug at the site of vascular injury. In afibrinogenaemia, this process cannot occur, resulting in a failure to form effective blood clots.

Clinical Presentation

Patients with afibrinogenaemia typically present with symptoms shortly after birth. Common clinical manifestations include:

- Umbilical cord bleeding: Excessive bleeding from the umbilical stump is often one of the first signs. - Mucosal bleeding: Frequent nosebleeds (epistaxis), gum bleeding, and gastrointestinal bleeding. - Menorrhagia: Women may experience heavy menstrual bleeding. - Hemarthrosis: Bleeding into joints, which can lead to joint damage if not managed properly. - Intracranial hemorrhage: A serious complication that can occur spontaneously or after minor trauma.

Diagnosis

The diagnosis of afibrinogenaemia is based on clinical evaluation and laboratory tests. Key diagnostic tests include:

- Prothrombin time (PT) and activated partial thromboplastin time (aPTT): Both are prolonged due to the absence of fibrinogen. - Fibrinogen assay: This test directly measures the level of fibrinogen in the blood, which is undetectable in afibrinogenaemia. - Genetic testing: Identifies mutations in the FGA, FGB, or FGG genes.

Treatment

Management of afibrinogenaemia focuses on preventing and controlling bleeding episodes. Treatment options include:

- Fibrinogen replacement therapy: Administered during bleeding episodes or prophylactically before surgical procedures. This can be done using cryoprecipitate or fibrinogen concentrate. - Antifibrinolytic agents: Such as tranexamic acid, to help stabilize clots. - Regular monitoring: Patients require regular follow-up with a hematologist to manage their condition effectively.

Prognosis

With appropriate management, individuals with afibrinogenaemia can lead relatively normal lives. However, they must be vigilant about avoiding situations that could lead to bleeding and adhere to their treatment regimen.

Also see

- Hypofibrinogenaemia - Dysfibrinogenaemia - Coagulation disorders - Hemophilia