Also known as: lupus antibody, LA, lupus inhibitor
Name: Lupus anticoagulant
Related tests: Antiphospholipid antibodies>, aPTT, Anti-cardiolipin antibodies, PT, LA-aPTT
Why is the test done?
To help explain a prolonged partial thromboplastin time (PTT) and/or a thrombotic event, to help find the cause of repeated miscarriages, and as part of the assessment of antiphospholipid syndrome; it is not a diagnostic test for lupus.
When is the test done?
When you have a prolonged PTT; when you have venous or arterial thromboembolism; when you have recurrent miscarriages, especially in the second and third trimesters
What sample is required?
A blood sample taken from a vein in the arm
What is being tested?
Lupus anticoagulant is a protein that increases the risk of developing blood clots in both veins and arteries. These clots can block blood flow anywhere in the body, leading to strokes, heart attacks, pulmonary embolism, deep vein thrombosis (usually clots in the legs) and repeated miscarriages, especially in the second and third trimesters (thought to be linked to clots forming in the blood vessels of the placenta). Lupus anticoagulant is an acquired condition. Although it is found most often in people with autoimmune diseases such as systemic lupus erythematosus (SLE), lupus anticoagulant can be found in people with HIV/AIDS or cancer, or who are taking medicines such as phenothiazines, procainamide and Fansidar. Lupus anticoagulant is thought to be present in 1-2% of the population and can develop even in people with no known risk factors.
Lupus anticoagulant (LA) is not a diagnostic test for lupus. It owes its name to its association with SLE. It often prolongs the partial thromboplastin time (PTT), a clotting test that, when prolonged, usually indicates a bleeding tendency, not thrombosis. LA prolongs the PTT test, as well as other related tests, because it binds to the phospholipids in the reagents (chemicals) used for the PTT test. In the body, phospholipids play a key role in clot formation. They are found mainly on the surface of platelets and help activate several clotting factors, proteins that are activated in sequence in response to tissue or vessel damage in a process called the coagulation cascade. Lupus anticoagulant is one of the three main antiphospholipid antibodies associated with an increased risk of thrombosis. The others are anti-cardiolipin antibodies and antibodies against beta-2 glycoprotein 1 (less common); together they give rise to antiphospholipid antibody syndrome (also called Hughes syndrome). A person can have one or more of these phospholipid-binding antibodies. Each of them interferes with the clotting process in ways that are not yet fully understood and, alone or together, they increase a person’s tendency to form clots.
While anti-cardiolipin and anti-beta2 glycoprotein 1 antibodies can be measured directly, there is no single test for LA. It is usually diagnosed by carrying out a panel of tests in sequence. These tests work on the principle that LA is not a specific inhibitor: it does not affect a specific clotting factor but binds to the phospholipids in the test, inhibiting them and prolonging the test times. For more information, see the section entitled “What does the test result mean?”
How is it used?
When is it requested?
What does the result mean?
Is there anything else I should know?
How is it used?
The LA test is used to help find the cause of unexplained thrombosis, repeated miscarriages or a prolonged PTT. It is requested to try to determine whether the prolonged PTT is due to a specific inhibitor (an antibody against a specific clotting factor) or to a non-specific inhibitor such as LA. It may be requested together with anti-cardiolipin and anti-beta2 glycoprotein 1 antibodies to check for antiphospholipid syndrome. If a person is positive for lupus anticoagulant, the test is repeated a few weeks later to see whether the antibodies were temporary. Occasionally lupus anticoagulant testing may be requested to help find the cause of a positive VDRL/RPR test for syphilis (both anti-cardiolipin antibodies and lupus anticoagulant can cause false positives on this test).
Since other inhibitors and analytical variables can cause abnormal test results, several tests are carried out to confirm the presence of LA. These typically include: PTT, prothrombin time (PT), dilute or modified Russell’s viper venom time (dRVVT or MRVVT), a hexagonal phase (II) phospholipid test (Staclot-LA test) or the kaolin clotting time. A thrombin time test may also be done to rule out heparin contamination (a medicine used for anticoagulant treatment), and a fibrinogen test to rule out a significant fibrinogen deficiency. These two conditions can prolong test results and interfere with the detection of lupus anticoagulant.
When is it requested?
Lupus anticoagulant testing is requested when a patient has had an unexplained thrombotic episode, has had recurrent miscarriages and/or as a follow-up to a prolonged PTT. If the lupus anticoagulant panel is positive, the person’s doctor may decide to repeat one or more of the tests a few weeks later to determine whether the lupus inhibitor is temporary or chronic. The doctor may also test for lupus anticoagulant when a patient has a positive anti-cardiolipin antibody, to assess whether that person has antiphospholipid antibody syndrome.
What does the result mean?
The results of each of the lupus anticoagulant tests indicate a greater or lesser likelihood of lupus anticoagulant. Although the tests done may vary, they usually start with a prolonged PTT.
• If the PTT or LA-PTT is prolonged and mixing with pooled normal plasma does not correct the result, an inhibitor is probably present. If the prolonged test corrects when phospholipids are added, lupus anticoagulant is probably present. (After heparin contamination, lupus anticoagulant is the most common reason for a prolonged PTT.)
• If the PTT is not prolonged, there may be no lupus anticoagulant, the reagents used for the test may contain too many phospholipids, or the test may not be sensitive enough to detect lupus anticoagulant. The LA-PTT test may need to be done.
• If a dRVVT or MRVVT is prolonged and does not correct when pooled normal plasma is added, but does correct when phospholipids are added, an antiphospholipid antibody is probably present.
• If the thrombin time is normal, heparin contamination can be ruled out.
• If the fibrinogen test is normal, there is probably enough fibrinogen to form a normal clot.
Platelet neutralisation (platelets are used as a source of phospholipids)
• Hexagonal phase II phospholipid test (Staclot-LA test)
• Kaolin clotting time
• Tissue thromboplastin inhibition test
• VDRL or RPR: these are tests for syphilis. The reagents are made of cardiolipin and may give false positive results with both anti-cardiolipin antibodies and lupus anticoagulant
• Clotting factors: these may be requested to rule out factor deficiencies that can cause a prolonged PTT and bleeding episodes
• Prothrombin time (PT)
Other tests may be requested in addition to lupus anticoagulant:
• Anti-cardiolipin and anti-beta2 glycoprotein I to check for antiphospholipid syndrome
• Platelet count: mild to moderate thrombocytopenia is often seen with lupus anticoagulant and may be caused by anticoagulant treatment (heparin)
Is there anything else I should know?
Patients on heparin or heparin substitutes (such as hirudin, danaparoid or argatroban) may have false positive lupus anticoagulant results, but those on warfarin (Coumadin) should not. If possible, lupus anticoagulant testing should be carried out before anticoagulant treatment starts. If a patient with thrombosis is positive for lupus anticoagulant, anticoagulant treatment may need to be extended and possibly intensified.
In addition to lupus anticoagulant testing, in some cases clotting factor VIII may need to be tested. Factor VIII inhibitors (specific antibodies against factor VIII) can lower factor VIII levels and cause false positive lupus anticoagulant results. High factor VIII levels, as seen in acute infections or during replacement therapy in patients with haemophilia A, can shorten the PTT, leading to temporary false negative lupus anticoagulant results.
1. Is sample collection critical for the lupus anticoagulant test?
2. How is lupus anticoagulant treated?
3. Which is more common: anti-cardiolipin or LA?
1. Is sample collection critical for the lupus anticoagulant test?
Yes. As well as heparin contamination, other pre-analytical variables can have a significant impact on the detection of lupus anticoagulant. The blood sample is collected in a special citrate tube and centrifuged to separate the plasma for testing. There must be the right amount of blood in the tube, and it must not be clotted. When the blood is centrifuged correctly, most of the platelets are removed from the sample. If there are too many platelets in the plasma sample, the test may be compromised (because platelets are a source of phospholipids). In addition, if the patient’s haematocrit is very high, the test results can be affected.
2. How is lupus anticoagulant treated?
No treatment is needed if there are no symptoms. If blood clots occur, patients are usually anticoagulated with heparin (injected under the skin or given intravenously (IV)), followed by oral warfarin (Coumadin) for several months. A higher than usual dose of warfarin may be needed, and treatment may need to be continued for longer. In some people with lupus anticoagulant, the risk of recurrent arterial and venous thrombotic episodes is relatively high. Some patients may need to take oral anticoagulants long term (even for life).
3. Which is more common: anti-cardiolipin or LA?
In general, anti-cardiolipin antibodies are more common than lupus anticoagulant. In patients with antiphospholipid antibody syndrome, anti-cardiolipin antibodies occur about five times more often than lupus anticoagulant. About sixty per cent of those with lupus anticoagulant will also have anti-cardiolipin antibodies.