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 prolong clotting time 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-containing reagents, usually PTT, the LA-sensitive PTT (known as PTT-LA) or dilute Russell viper venom test (DRVVT). All of these tests measure the time it takes (in seconds) for a plasma 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.
LA may increase the risk of developing blood clots in both the veins and arteries, often in the veins in the legs (known as deep vein thrombosis or 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, organ failures, 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 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 in a woman
- An unexplained prolonged partial thromboplastin time (PTT, aPTT 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, or is due to deficiency in coagulation factor(s).
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, antithrombin, 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 initially (known as LA-Screen). The most sensitive tests are dilute Russell viper venom test (DRVVT) and a LA-sensitive PTT (PTT-LA), one that uses reagents containing low levels of phospholipid. 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 (known as LA-Confirm): 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). The results are then compared to that of the LA-Screen, and an interpretation is made by a laboratory technologist or pathologist.
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 that is unexplained
If results indicate the presence of lupus anticoagulant (LA), 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 care 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 laboratory technologists and/or physicians with experience with excessive clotting disorders testing.
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.
Results that indicate the presence of LA may mean that a person’s signs and symptoms are due, at least in part, to LA. Results that indicate that LA is NOT present may mean that signs and symptoms, such as a prolonged PTT, are due to some other cause such as deficiency on coagulation factor(s).
For example, if LA is positive on two or more occasions at least 12 weeks apart, the results may indicate antiphospholipid syndrome. 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.
Some other tests may be done to help confirm the diagnosis of a lupus anticoagulant and/or to help rule out other causes of a prolonged PTT. Examples include:
- Coagulation factor assays (e.g., fibrinogen) – 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 versus factor deficiency.
- 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.
- Thrombin time – if a thrombin time test is normal, then heparin contamination is excluded as a cause of prolonged PTT.
What are some additional details on LA testing results?
The following table summarizes some LA testing results that may be seen.
|Step 1||LA-sensitive PTT (PTT-LA) and/or dilute Russell viper venom test (DRVVT)||Normal||Usually no further testing is done. If there is a strong suspicion of the presence of an inhibitor, then testing may be repeated.|
|Prolonged||Possible inhibitor present; see Step 2|
|Step 2||Mixing study: Mix equal parts patient plasma with normal pooled plasma and perform PTT-LA or DRVVT||Normal||The initial test results were prolonged due to a cause other than an inhibitor, i.e., deficiency in coagulation factor(s).|
|Prolonged||If mixing patient plasma with normal pooled plasma does not “correct” the result, then it is likely that lupus anticoagulant is present; see Step 3|
|Step 3||Confirmation (correction or neutralization test): perform PTT-LA or DRVVT again but add excess phospholipids (e.g., hexagonal phase phospholipid neutralization assay). A normalized ratio is calculated by dividing this result into the result of PTT-LA or DRVVT without excess phospholipids.||Positive (high ratio)||If the ratio is above a specified cutoff, then presence of lupus anticoagulant is suggested.|
|Negative (low ratio)||A specific inhibitor rather than lupus anticoagulant may be present. Tests for antibodies directed against coagulation factors, specifically factor VIII, may be performed. Unlike LA that may cause clotting in the body, a factor specific inhibitor can cause severe bleeding.|
Based on the International Society of Thrombosis and Hemostasis (ISTH) recommendations, there are four criteria that must be met to confirm the presence of LA:
- Prolonged result on at least one of two coagulation tests that are dependent on phospholipids, such as PTT-LA or DRVVT
- Prolonged result on a mixing study (evidence of clotting inhibition)
- Shortened clotting time occurs after adding excess phospholipids (demonstrates dependence of the inhibitor on phospholipids)
- Ruling out coexisting specific coagulation factor inhibitor, such as factor VIII, which could result in catastrophic bleeding if not identified
Is there anything else I should know?
After heparin contamination, a lupus anticoagulant is the most common reason for a prolonged PTT.
Occasionally, LA 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 syphilis tests.
Lupus anticoagulants may also be present 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 harmful blood clot (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.
Is sample collection critical for lupus anticoagulant (LA) testing?
Yes. Besides heparin contamination, other pretest variables may have a significant impact on detecting the lupus anticoagulant. The blood sample is collected in a special citrated tube and centrifuged to remove the plasma for testing. There must be the proper amount of blood in the tube and it cannot be clotted. When the blood is properly centrifuged, most of the platelets are removed from the test sample. If there are too many platelets in the plasma sample, test results may be compromised because platelets are a source of phospholipids. Also, if a person’s hematocrit is very high, test results may be affected.
Is there anything I can do to get rid of lupus anticoagulant?
No. You cannot get rid of this autoantibody through any actions on your part such as lifestyle changes. There is no cure, but if you experience signs and symptoms related to LA, there are treatments available that can help decrease your risk of excessive clotting.
How is a person with lupus anticoagulant treated?
No treatment is required if someone does not have any symptoms. If blood clots do occur, patients are usually treated with anticoagulants such as heparin (which is injected under the skin or given intravenously) followed by oral warfarin (COUMADIN®) therapy for several months. Higher than usual doses of warfarin may be required, and the treatment may need to be continued for a longer period of time. In someone with the lupus anticoagulant, the risk of recurrence of both arterial and venous thrombotic episodes is relatively high. Some people may need to be on long-term (even life-long) oral anticoagulation. New oral anticoagulation drug may also be prescribed by your health care provider if you need long-term therapy.
Who is at risk for antiphospholipid syndrome?
Antiphospholipid syndrome (APS) may affect anyone but is most frequently seen in women of child-bearing age and in those with another autoimmune disorder. According to the March of Dimes, APS is the most common acquired excessive clotting disorder (thrombophilia), affecting up to 5% of pregnant women.
If it is suspected that I have an excessive clotting disorder, what tests other than LA might my doctor use to evaluate my condition?
Other tests used to evaluate excessive clotting may include factor V Leiden mutation and prothrombin gene G20210A mutation, other antiphospholipid antibodies, homocysteine, protein C and protein S, and antithrombin.
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