Hereditary antithrombin deficiency

Other Names:

Congenital AT-III deficiency; 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.

Hereditary antithrombin deficiency, also known as antithrombin III deficiency or AT III 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 (deep vein thrombosis or DVT) and clots that lodge in the lungs (pulmonary embolism or PE).

Risk factors

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.

Cause

Hereditary antithrombin deficiency is caused by mutations in the SERPINC1 gene.

This gene provides instructions for producing a protein called antithrombin (previously known as antithrombin III). This protein is found in the bloodstream and is important for controlling blood clotting. Antithrombin blocks the activity of proteins that promote blood clotting, especially a protein called thrombin.

Most of the mutations that cause hereditary antithrombin deficiency change single protein building blocks (amino acids) in antithrombin, which disrupts its ability to control blood clotting. Individuals with this condition do not have enough functional antithrombin to inactivate clotting proteins, which results in the increased risk of developing abnormal blood clots.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Antithrombin III Deficiency is inherited in an autosomal dominant manner.

This disease is affecting one in thousand people annually. It is type of multifactorial disease where both genetics and environment affect the procoagulant and anticoagulant forces, finally leading the ATIII deficiency. Various mutations in genes, such as deletion or addition of genes, for anticoagulant proteins such as protein C, antithrombin or protein S are one of the risk factors.

Symptoms

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Reduced antithrombin antigen
• Reduced antithrombin III activity

30%-79% of people have these symptoms Deep venous thrombosis(Blood clot in a deep vein) Pregnancy exposure Pulmonary embolism(Blood clot in artery of lung) Recurrent thromboembolism Superficial thrombophlebitis

5%-29% of people have these symptoms

• Arterial thrombosis(Blood clot in artery)
• Hepatic vein thrombosis(Blood clot in liver vein)
• Mesenteric venous thrombosis
• Portal vein thrombosis(Blood clot in portal vein)
• Recurrent spontaneous abortion
• Retinal vein occlusion

1%-4% of people have these symptoms Cerebral venous thrombosis(Blood clot in cerebral vein)

Diagnosis

Different laboratory tests can be performed to investigate for antithrombin III deficiency. First, numerical analysis for antithrombin can be performed. A lower antithrombin III level increases the risk of venous thrombosis and pulmonary embolism. Second, Anticardiolipin antibodies (immunoglobulin G [IgG] and IgM class) can be injected. Third, antigen activity and total tests for Protein C and Protein S can be checked to see if the genes of their proteins have been mutated.

Fourth, Prothrombin time (PT) and activated partial thromboplastin time (aPTT) can be calculated. Finally, Factor V Leiden test can also be performed in order to check blood clotting and adhesion of platelets

First of all, echocardiography is performed to all patients suffering from antithrombin III deficiency. These patients will be first go through the blood test to find a sign go arterial thrombus, then echocardiography can be tested. Second, doppler ultrasonography is usually performed at the earlier stage than echocardiography to compress. It is used to find the resolution of an acute thrombus. Finally, ventilation-perfusion scanning is test to check for images of pulmonary thrombosis.

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. surgery be necessary, individuals with hereditary antithrombin deficiency may receive antithrombin III concentrate or fresh frozen plasma to boost antithrombin levels.

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®)Prevention of peri-operative and peri-partum thromboembolic events, in hereditary antithrombin deficient patients.
• Antithrombin III (human) (Brand name: Thrombate III)Antithrombin III (human) (Brand name: Thrombate III)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. 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.