Antithrombin

Antithrombin testing is primarily requested to investigate the cause of recurrent venous thrombosis and is normally part of a wider ‘thrombophilia screen’. The antithrombin activity test is performed before the antigen test, to evaluate whether the total amount of functional antithrombin is normal. Activity will be decreased with both Type 1 and Type 2 antithrombin deficiencies, so this test can be used as an initial screen for both. If the antithrombin activity is low, then the antithrombin antigen test is performed to determine the quantity of antithrombin present. If a deficiency is detected, both antithrombin tests are repeated at a later date to confirm test findings. Antithrombin testing may be used to evaluate patients not responding as expected to heparin.

Antithrombin activity testing is requested, along with other proteins involved in clotting regulation (such as Protein S and Protein C), when a patient has been experiencing recurrent venous thrombosis. Antithrombin should be measured after a blood clot has been treated and resolved as both the presence of the clot, and the therapy used to treat it, will affect antithrombin results.

Antithrombin testing may be requested in the close blood relatives of someone with low levels of antithrombin to see if they share the problem.

Antithrombin testing may be used when a patient is not responding as expected to heparin anticoagulation - when unusually high doses of heparin are necessary to achieve the desired level of anticoagulation.

Decreased antithrombin activity and decreased quantities of antithrombin antigen suggest a Type 1 antithrombin deficiency. In this case, the activity is decreased because there is less antithrombin available to participate in clotting regulation. Reduced antithrombin activity and normal levels of antithrombin antigen suggest a Type 2 antithrombin deficiency. This means that there is sufficient antithrombin, but it is not functioning as it should.

If the antithrombin activity is normal, then the antithrombin antigen test is usually not performed. In this case, the antithrombin is functioning adequately and the recurrent thrombotic episodes being investigated are likely due to another cause.

Increased levels of antithrombin are not usually considered a problem.  They may be seen with:

• Acute cholestasis
• Kidney transplant
• Vitamin K deficiency
• Warfarin (coumadin) anticoagulation therapy (sometimes)

Testing for antithrombin deficiency is not recommended unless the patient’s condition is stable. Temporarily or chronically decreased antithrombin levels may be seen with conditions that affect its consumption or production, such as:

• an acute or chronic condition characterised by the consumption of clotting factors. An affected patient may bleed and/or thrombose. 
• DVT (deep vein thrombosis – a blood clot usually in a deep leg vein)
• Pulmonary embolism (a clot which travels in the circulation to the lung from another part of the body)
• Pregnancy
• Liver disease
• Nephrotic syndrome
• Protein-losing condition
• Neonates during the first few days of life
• Oestrogen therapy
• Metastatic tumours
• Chemotherapy with asparaginase

If a patient with an antithrombin deficiency also has other coagulation risks, such as a Protein C or S deficiency, a Factor V Leiden mutation, or oral contraceptive use, then they may be at a significantly elevated risk of developing a blood clot.

Antithrombin deficiency can increase the risk of recurrent miscarriage.

Patients with antithrombin deficiency may need to take preventative anticoagulation prior to medical or surgical procedures.

Antithrombin concentrates may be used to temporarily correct acute or chronic antithrombin deficiencies.

Genetic testing of the antithrombin gene (SERPINC1) may be performed in select cases to identify the mutation causing the faulty gene. This can determine whether the patient has one defective gene (heterozygous) or two defective genes (homozygous) and can confirm the type of antithrombin deficiency (Type 1 or 2). Some mutation types may be associated with a higher or lower risk of thrombosis.

If you have a personal or strong family history of recurrent blood clots, your doctor may do a physical to determine your general state of health and request a series of tests to determine your risk of having a hypercoagulable disorder. The more inherited or acquired risk factors you have (such as a Factor V Leiden or PT 20210 mutation, or a Protein C or S deficiency), the higher your relative risk of clotting. This risk can be further increased if you are overweight, sedentary, smoke, and/or take oral contraceptives. It is important to remember, however, that any overall relative risk that is determined is still a statistical risk. No one can predict whether a particular patient will actually experience recurrent clotting.