To help investigate the cause of recurrent inappropriate blood clotting; to help diagnose an antithrombin deficiency
A couple of months after getting a blood clot (thrombotic episode) or when you are not responding as expected to heparin anticoagulation therapy
A blood sample drawn from a vein in your arm
Typically, no test preparation is needed. Note that testing for antithrombin deficiency is not recommended if a person's condition may affect the antithrombin level (e.g., DIC) and/or after the person has been treated with heparin for a blood clot.
Antithrombin is a protein produced by the liver that helps regulate blood clot formation (i.e., a naturally-occurring mild blood thinner). Antithrombin testing measures the activity (function) and the amount (quantity) of antithrombin in an individual's blood and is used to evaluate the person for excessive blood clotting.
Normally, when a blood vessel is injured, the body initiates a complex process called hemostasis to form a blood clot and prevent further blood loss. Part of this complex process involves the activation of several proteins called coagulation factors in a series of steps referred to as the coagulation cascade. Antithrombin helps to regulate this process by inhibiting the action of several activated coagulation factors, including thrombin and factors Xa, IXa, and XIa, to slow down the process and prevent excessive or inappropriate clotting (thrombosis).
People with an excessive clotting disorder due to an inherited or acquired antithrombin deficiency are at increased risk of developing blood clots, especially in deep veins such as in the legs (known as deep venous thrombosis or DVT). Inherited deficiencies are rare, affecting about 1 in 5,000 people. For people who inherit one defective gene and one normal gene (heterozygous), episodes of inappropriate blood clot formation typically start at about 20 to 30 years of age. Very rarely, a person may inherit two defective antithrombin genes, resulting in severe clotting problems soon after birth.
Acquired antithrombin deficiencies may occur at any age. They are associated with a variety of conditions that cause decreased production, excessive consumption, or loss of antithrombin. These conditions include liver disease, extensive thrombosis, disseminated intravascular coagulation (DIC), blood loss, cancer, and nephrotic syndrome – a form of kidney disease.
There are two types of antithrombin deficiency. With type 1, antithrombin functions normally, but the quantity is insufficient. With type 2, there is a sufficient quantity of antithrombin produced, but it is dysfunctional. These types can be differentiated and assessed by testing:
- Antithrombin activity, which evaluates the function of antithrombin
- Antithrombin antigen, which measures the quantity of antithrombin present
- How is the test used?
Antithrombin testing is primarily ordered, along with other tests for excessive clotting disorders, to investigate the cause of recurrent blood clot formation (thrombosis). Testing evaluates the activity (function) and the amount (quantity) of antithrombin and helps identify antithrombin deficiency.
The activity test is performed first, to evaluate whether the total amount of functional antithrombin is normal. If the antithrombin activity is low, then the antithrombin antigen test is performed to determine the quantity of antithrombin present. These two tests can be used to differentiate between type 1 and type 2 antithrombin deficiencies. If a deficiency is detected, both antithrombin tests are typically repeated at a later date to confirm test findings.
Antithrombin testing may sometimes be used to evaluate people who are not responding as expected to heparin. Heparin is an anticoagulant drug that is given to people who have a blood clot or are at an increased risk of forming inappropriate blood clots. The effects of heparin are mediated by antithrombin. Heparin can greatly increase antithrombin activity, thus inhibiting formation of blood clots, but those who are antithrombin-deficient are resistant to heparin treatment.
- When is it ordered?
Antithrombin activity testing is ordered, along with other tests for excessive clotting disorders (such as protein C and protein S and lupus anticoagulant), when a person has been experiencing recurrent blood clots. Antithrombin testing should be performed to evaluate an individual for an excessive clotting disorder only 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 also be ordered when a person is not responding as expected to heparin anticoagulation, when unusually high doses of heparin are necessary to achieve the desired level of anticoagulation.
- What does the test result mean?
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 protein, but it is not functioning as it should. In either case, a deficiency increases the affected person's risk of developing an inappropriate blood clot.
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 a cause other than an antithrombin deficiency.
Temporarily or chronically decreased antithrombin levels may be seen with conditions that affect its consumption or production, such as:
- DIC (disseminated intravascular coagulation), an acute or chronic condition characterized by the consumption of clotting factors; an affected person may bleed and/or clot.
- DVT (deep vein thrombosis – a blood clot usually in a deep leg vein)
- Liver disease
- Nephrotic syndrome
- Protein-losing condition
- Pulmonary embolism
- Heparin therapy (temporary lower antithrombin level)
- Infants during the first few days of life (about 50% of healthy adult level)
- Estrogen therapy
Increased levels of antithrombin are not usually considered a problem.
- Is there anything else I should know?
If a person 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 the person may be at a significantly elevated risk of developing a blood clot.
Antithrombin deficiency can increase the risk of recurrent miscarriage.
People with antithrombin deficiency may need preventive anticoagulation therapy prior to medical or surgical procedures.
Antithrombin concentrates and recombinant antithrombin are now available as a medication to temporarily correct acute or chronic antithrombin deficiencies.
- How can I determine my risk of developing a blood clot?
If you have a personal or strong family history of recurrent blood clots, your healthcare provider may perform an examination to determine your general state of health and order a series of tests to determine your risk of having an excessive clotting 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, have hypertension, 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 person will actually experience recurrent clotting.
- Should I tell my dentist or other healthcare providers about my antithrombin deficiency?
Yes. This is important information that your healthcare providers should know about as it affects your body's ability to clot appropriately during and after a medical procedure.
- Can I do anything to change my antithrombin activity or quantity?
In general, no. If you have an acquired deficiency that is related to an underlying condition, such as liver disease, then treating the condition may ease or eliminate the deficiency. If needed, your healthcare provider may treat you with antithrombin (as a medication) to temporarily correct the deficiency.