Antithrombin III deficiency

A genetic disorder affecting blood clotting

Antithrombin III deficiency is a genetic disorder that affects the body's ability to regulate blood clotting. It is characterized by a deficiency in antithrombin, a protein that helps prevent abnormal blood clot formation. This condition can lead to an increased risk of thrombosis, which is the formation of blood clots within blood vessels.

Pathophysiology

Antithrombin is a serine protease inhibitor (serpin) that plays a crucial role in the regulation of the coagulation cascade. It primarily inhibits thrombin and factor Xa, which are key enzymes in the clotting process. In individuals with antithrombin III deficiency, the reduced levels or activity of antithrombin lead to an increased tendency for blood clot formation, as the inhibitory effect on thrombin and factor Xa is diminished.

Types

Antithrombin III deficiency can be classified into two main types:

• Type I deficiency: This is a quantitative deficiency where there is a reduced level of antithrombin in the blood.
• Type II deficiency: This is a qualitative deficiency where the level of antithrombin is normal, but its function is impaired.

Genetics

Antithrombin III deficiency is usually inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene can cause the disorder. The gene responsible for antithrombin production is the SERPINC1 gene, located on chromosome 1. Mutations in this gene can lead to either type I or type II deficiency.

Clinical Manifestations

Individuals with antithrombin III deficiency may experience recurrent episodes of venous thromboembolism (VTE), which includes conditions such as deep vein thrombosis (DVT) and pulmonary embolism (PE). Symptoms of DVT may include swelling, pain, and redness in the affected limb, while PE may present with shortness of breath, chest pain, and coughing up blood.

Diagnosis

Diagnosis of antithrombin III deficiency involves measuring the level and activity of antithrombin in the blood. A reduced level or activity suggests the presence of the deficiency. Genetic testing can also be performed to identify mutations in the SERPINC1 gene.

Management

Management of antithrombin III deficiency focuses on preventing thrombotic events. This may include the use of anticoagulant medications such as heparin or warfarin. In some cases, antithrombin concentrates may be administered, especially during high-risk situations such as surgery or pregnancy.

Prognosis

With appropriate management, individuals with antithrombin III deficiency can lead normal lives. However, they remain at an increased risk for thrombotic events, and lifelong anticoagulation therapy may be necessary.

Related pages

• Thrombophilia
• Coagulation
• Deep vein thrombosis
• Pulmonary embolism