Antithrombin iii deficiency

A rare disorder characterized by the presence of low levels of antithrombin iii which prohibits the formation of blood clots.

Clinical features

It may lead to venous thrombosis and pulmonary embolism.

Antithrombin-gene-strand-switch

Types

Acquired and genetic types.

Congenital AT-III deficiency

• Also known as antithrombin III Deficiency;
• Congenital Antithrombin III Deficiency;
• Thrombophilia due to antithrombin III deficiency;
• Inherited antithrombin deficiency;
• Hereditary thrombophilia due to congenital antithrombin deficiency;
• Hereditary thrombophilia due to congenital antithrombin 3 deficiency

Inheritance

It may be inherited, usually in an autosomal dominant pattern, or acquired.

Autosomal Dominant Inheritance

Clinical features

• Hereditary antithrombin deficiency, is a disorder in which individuals are at increased risk for developing blood clots.
• The type of blood clots seen in individuals with this condition are typically clots that form in the deep veins of the leg, DVT, leading to risk of PE.
• Approximately 50% of individuals with hereditary antithrombin deficiency will develop one or more clots in their lifetime, usually after adolescence.
• Factors that may increase the likelihood of clotting include pregnancy, the use of oral contraceptives, surgery, increasing age, and a lack of movement.
• Hereditary antithrombin deficiency is caused by mutations in the SERPINC1 gene and is typically inherited in an autosomal dominant manner.

Symptoms

Symptoms vary - most common symptoms are DVT, PE, which happens on a recurrent basis

80%-99% of people have these symptoms

• Reduced antithrombin antigen
• Reduced antithrombin III activity

30%-79% of people have these symptoms

• Deep venous thrombosis
• Loss of pregnancy]]
• Pulmonary embolism
• Recurrent thromboembolism
• Superficial thrombophlebitis

5%-29% of people have these symptoms

• Arterial thrombosis
• Hepatic vein thrombosis
• Mesenteric venous thrombosis
• Portal vein thrombosis
• Recurrent spontaneous abortion
• Retinal vein occlusion

1%-4% of people have these symptoms

• Cerebral venous thrombosis

Less common symptoms

• Arterial occlusion
• Recurrent thrombophlebitis

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis.

Genetic testing

The Genetic Testing Registry (GTR) is a useful resource

Treatment

• Once a patient with hereditary antithrombin deficiency develops a clot, anticoagulation therapy (usually Warfarin) is often indicated.
• The duration of therapy after a first clot, especially in children, is a matter of some controversy, but therapy is generally continued for 3-6 months.
• Individuals who experience a second clot are at a significant risk for future clotting and are candidates for long-term Warfarin therapy. Asymptomatic individuals are often not treated with anticoagulation therapy.
• Should surgery be necessary, individuals with hereditary antithrombin deficiency may receive antithrombin III concentrate or fresh frozen plasma to boost antithrombin levels.

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

Recombinant human antithrombin (Brand name: Atryn®) - Manufactured by GTC Biotherapeutics, Inc.

FDA-approved indication: Prevention of peri-operative and peri-partum thromboembolic events, in hereditary antithrombin deficient patients.

Antithrombin III (human) (Brand name: Thrombate III) - Manufactured by Grifols United States

FDA-approved indication: For replacement therapy in congenital deficiency of AT-III for prevention and treatment of thrombosis and pulmonary emboli.

Prognosis

The prognosis depends on the degree of antithrombin deficiency, the nature of the clots formed, and the number of clots formed.

Anticoagulation

Patients with recurring clots are more likely to suffer a life-threatening clotting event in the future and are best treated with indefinite Warfarin therapy after careful evaluation of the potential risks and benefits.

Also see

• Blood clots
• DVT
• Pulmonary embolism
• Antithrombin

Antithrombin iii deficiency Resources
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