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 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 of unknown cause; when you have had recurrent miscarriages
A blood sample obtained by inserting a needle into a vein in your arm
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:
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.
LA may increase the risk of developing blood clots in both the veins and arteries, often in the veins in the legs (knowns 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.
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:
LA testing may also be used:
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:
Lupus anticoagulant testing is ordered along with other tests when:
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 healthcare 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.
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.
(See below for additional details on LA testing results.)
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:
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)||
|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||
|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:
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.
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.
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 (see below).
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 healthcare provider if you need long-term therapy.
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.
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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