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Lupus Anticoagulant Testing


At a Glance

Why Get Tested?

To help investigate the cause of a blood clot (thrombotic episode); to evaluate a prolonged partial thromboplastin time (PTT); to help determine the cause of recurrent miscarriages, or as part of an evaluation for antiphospholipid syndrome; the tests are not used to diagnose the chronic autoimmune disorder systemic lupus erythematosus (SLE), commonly known as lupus.

When to Get Tested?

When you have had signs and symptoms of a blood clot in a vein or artery (known as thrombosis or thromboembolism); when you have a prolonged PTT test; when you have had recurrent miscarriages

Sample Required?

A blood sample obtained by inserting a needle into a vein in your arm

Test Preparation Needed?

None

The Test Sample

What is being tested?

Lupus anticoagulants (LA) are autoantibodies produced by the immune system that mistakenly attack certain components of the body's own cells. They specifically target phospholipids as well as the proteins associated with phospholipids that are found in the outer-most layer of cells (cell membranes). These autoantibodies interfere with the blood clotting process in a way that is not fully understood and increase a person's risk of developing a blood clot. Lupus anticoagulant testing is a series of tests that detect the presence of LA in the blood.

The lupus anticoagulant test's name may seem odd or confusing for two reasons:

  • Lupus anticoagulants were so-named because they were first found among patients with lupus, but LA testing is not used to diagnose the autoimmune disorder and LA are frequently absent in people with lupus. LA may also occur in individuals with other conditions and in people who take certain medications. The antibodies are present in about 2-4% of the general population and may develop in people with no known risk factors.
  • The term "anticoagulant" is part of the name because LA actually reduce clotting in laboratory tests that are used to evaluate coagulation. For example, they inhibit the chemical reactions that lead to clotting in the partial thromboplastin time (PTT), a test routinely used to evaluate clotting. However, the presence of LA in the human body is associated with an increased risk of developing inappropriate blood clots. Importantly, lupus anticoagulant itself does not cause bleeding in the body.

There is no single test for the detection of lupus anticoagulant and it cannot be measured directly. The presence of LA is usually determined by using a panel of sequential tests for which there is no standardization.

  • Initial testing typically involves one or more tests that depend on phospholipid reagents, usually PTT, the LA-sensitive PTT (PTT-LA) or dilute Russell viper venom test (DRVVT). All of these tests measure the time it takes (in seconds) for a sample to clot; LA prolongs that time.
  • Depending on the results of these initial tests, certain follow-up tests are performed to either confirm or exclude the presence of lupus anticoagulant. For more on this, see the section titled "How is it used?".

LA may increase the risk of developing blood clots in both the veins and arteries, often in the veins in the legs (deep vein thrombosis, DVT). These clots may block blood flow in any part of the body, leading to stroke, heart attack, or pulmonary embolism. LA is also associated with recurrent miscarriages. It has been suggested that LA causes clots to form that block blood vessels of the placenta, affecting growth of the developing baby, and that LA may also directly attack the tissue of the placenta, affecting its development.

The lupus anticoagulant is one of three primary antiphospholipid antibodies that are associated with an increased risk of thrombosis and antiphospholipid antibody syndrome (APS), an autoimmune disorder characterized by excess blood clot formation and pregnancy complications. The other two are cardiolipin antibodies and beta-2 glycoprotein 1 antibody. Individually and together, they increase a person's tendency to clot inappropriately. People with APS are at greater risk for clotting if they test positive for all three antibodies. However, thrombosis appears more common in people with LA.

Not everyone with antiphospholipid antibodies will develop symptoms. Antiphospholipid antibodies are present in about 5% of healthy individuals.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

The Test

How is it used?

Lupus anticoagulant testing is a series of tests used to detect lupus anticoagulant (LA) in the blood. LA is an autoantibody associated with excess blood clot formation. LA testing may be used to help determine the cause of:

  • An unexplained blood clot (thrombosis) in a vein or artery
  • Recurrent miscarriages
  • An unexplained prolonged PTT test (PTT measures the time it takes in seconds for a person's blood sample to clot in a test tube after reagents are added.) LA testing helps determine whether a prolonged PTT is due to a specific inhibitor, such as an antibody against a specific coagulation factor, or to a nonspecific inhibitor like the lupus anticoagulant.

LA testing may also be used:

  • Along with tests for cardiolipin antibody and anti-beta2-glycoprotein I to diagnose antiphospholipid syndrome (APS)
  • Along with tests such as factor V Leiden or proteins C and S to help diagnose an excessive clotting disorder (thrombophilia)
  • To determine whether the lupus anticoagulant is temporary (transient) or persistent

LA cannot be measured directly and there is no single test or standardized procedure to detect the presence of LA in the blood. A series of tests is used to confirm or rule out the autoantibody:

  • It is recommended that two tests be used to detect lupus anticoagulant. The most sensitive tests are dilute Russell viper venom test (DRVVT) and a LA-sensitive PTT (PTT-LA), one that uses low levels of phospholipid reagents. Follow-up testing is performed to confirm or exclude the presence of lupus anticoagulant. These may include:
  • Mixing study: an equal volume of patient plasma is mixed with "normal" pooled plasma and a PTT or DRVVT is performed on this mixture.
  • Correction/neutralization: an excess of phospholipids is added to the patient sample and a PTT-LA or DRVVT is performed. (When PTT-LA is measured, the assay is called a hexagonal phase phospholipid neutralization assay).

When is it ordered?

Lupus anticoagulant testing is ordered along with other tests when:

  • Someone has had an unexplained blood clot in a vein or artery; signs and symptoms can range from pain, swelling, and discoloration in the leg in the case of deep vein thrombosis (DVT) to fatigue, sweating, and rapid breathing with a pulmonary embolism (PE).
  • An individual has signs and symptoms of APS; these may be similar to the ones mentioned above.
  • A woman experiences recurrent miscarriages
  • A person has a prolonged PTT test

If results indicate the presence of lupus anticoagulant, testing is usually repeated about 12 weeks later to confirm that it is still present, especially for individuals being tested for APS.

When a person is initially negative for lupus anticoagulant but has an autoimmune disease such as lupus, a health practitioner may occasionally repeat one or more of the lupus anticoagulant screening tests, usually the PTT, to determine whether the antibody has developed since the last time the test was performed. This is done because the person has the potential to develop the lupus anticoagulant at any time.

What does the test result mean?

The results of the series of LA tests either lead toward or away from the likelihood of having LA. The laboratory report may be somewhat complicated, but it usually provides an interpretation of the results and states whether LA is present or absent. LA testing results, like those of other tests for clotting disorders, are difficult to interpret and are best evaluated by physicians with experience with excessive clotting disorders.

Although the initial tests performed for LA may vary, they usually begin with a PTT that is prolonged. A PTT that is normal (not prolonged) may mean that there is no LA present. However, the test may not be sensitive enough to detect LA and the LA-sensitive PTT (PTT-LA) may need to be done.

Additional details on LA testing results

Lupus anticoagulant testing is often done in conjunction with tests for cardiolipin antibody and anti-beta2-glycoprotein I antibodies to help diagnose antiphospholipid syndrome. The results are interpreted together, along with clinical criteria, in order to make a diagnosis.

Results of other tests that may be performed to help rule out other causes of a prolonged PTT include:

  • If a thrombin time test is normal, then heparin contamination is excluded as a cause of prolonged PTT.
  • If a fibrinogen test is normal, then it is likely that there is sufficient fibrinogen for clot formation.

Other tests that may be done to help confirm the diagnosis of a lupus anticoagulant include:

  • Coagulation factor assays – these may be ordered to rule out factor deficiencies that may cause a prolonged PTT and bleeding episodes; a panel of factor assays may also help in detecting lupus anticoagulant.
  • Complete blood count (CBC) – the CBC test includes a platelet count; mild to moderate thrombocytopenia (low platelet count) is often seen along with the lupus anticoagulant; moderate to severe thrombocytopenia may develop in patients receiving anticoagulant (heparin) therapy for lupus anticoagulant-associated thrombosis.
  • Tissue thromboplastin inhibition test (rarely performed nowadays)

Is there anything else I should know?

After heparin contamination, a lupus anticoagulant is the most common reason for a prolonged PTT.

Occasionally, testing may be ordered to help determine the cause of a positive VDRL/RPR test for syphilis because cardiolipin antibodies may produce a false-positive result with these tests.

Lupus anticoagulants may also occur in individuals with autoimmune diseases, infections such as HIV/AIDS, inflammation, cancers, and in people who take certain medications, such as phenothiazines, penicillin, quinidine, hydralazine, procainamide, and fansidar.

Patients on heparin or heparin substitute (such as hirudin, danaparoid, or argatroban) anticoagulation therapy may have false-positive results for lupus anticoagulant. Warfarin (COUMADIN®) anticoagulant therapy may also cause false test results if levels of coagulation factor II, VII, IX and X are significantly decreased. If possible, lupus anticoagulant testing should be done prior to the start of anticoagulation therapy.

If someone with a thrombosis has a lupus anticoagulant, it is usually necessary to prolong and possibly increase the intensity of the person's anticoagulation therapy.

For someone with a confirmed lupus anticoagulant, the usual anticoagulation monitoring test (e.g., PTT for heparin, PT/INR for warfarin) is unreliable, so alternative testing should be used for therapy monitoring. For example, chromogenic anti-Xa and chromogenic Xa assays should be used for heparin and warfarin monitoring, respectively.



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