Lupus Anticoagulant

Lupus anticoagulant testing is used to help determine the cause of an unexplained thrombosis, patients that have had a stroke, recurrent foetal loss, or a prolonged aPTT test. It is used to help determine whether a prolonged aPTT is due to a specific inhibitor (an antibody against a specific coagulation factor), or to a non-specific inhibitor, like the lupus anticoagulant. It may be used with anticardiolipin antibody and anti-beta2-glycoprotein-1 assay to check for the presence of antiphospholipid syndrome. If someone tests positive for the lupus anticoagulant, the test may be done again in several weeks to see if the antibody was due to a temporary condition or is a chronic issue. Occasionally lupus anticoagulant testing may be ordered to help determine the cause of a positive VDRL/RPR test for syphilis (both anticardiolipin and lupus antibodies will test false positive with these tests).

Because there are other inhibitors and analytical variables that can cause abnormal test results, several different tests are used to confirm the presence of a lupus anticoagulant. Typically these may include: aPTT, prothrombin time (PT), dilute or modified Russell viper venom screen (dRVVT or MRVVT), and a hexagonal (II) phase phospholipid assay (Staclot-LA test) or kaolin clot time. A thrombin time test may also be done to rule out heparin contamination (this is a drug used for anticoagulant therapy), and a fibrinogen test may be done to rule out hypofibrinogenaemia. These two conditions can cause prolongations in the test results and interfere with lupus anticoagulant detection.

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 aPTT test. If a lupus anticoagulant panel is positive your doctor may want to repeat one or more of the tests several weeks later to determine whether the lupus inhibitor is transitory or chronic.

Your doctor may also want to test for the lupus anticoagulant when you have a positive anticardiolipin antibody, to evaluate whether you have antiphospholipid syndrome.

If you are negative for the lupus anticoagulant but have an autoimmune disease, such as SLE or a mixed connective tissue disorder, your doctor may occasionally request one or more of the lupus anticoagulant screening tests, usually the aPTT, to determine whether or not you may have developed the lupus anticoagulant. This is most likely if you have developed symptoms suggestive of blood clot formation, such as pain and swelling in the extremities, shortness of breath, headaches, etc.

The results of each of the lupus anticoagulant tests either lead towards or away from the likelihood of having a lupus anticoagulant. Although the tests done may vary, they usually begin with a prolonged aPTT.

• If the aPTT or LA-aPTT is prolonged, and mixing it with normal pooled plasma does not “correct” the result then it is likely that there is an inhibitor present. If the prolonged test corrects when phospholipid is added then it is likely that a lupus anticoagulant is present. (After heparin contamination, a lupus anticoagulant is the most common reason for a prolonged aPTT).
• If the aPTT is not prolonged, there may not be a lupus anticoagulant or the test reagents may contain too much phospholipid, the test may not be sensitive enough to pick up the lupus anticoagulant. The LA sensitive aPTT may need to be done.
• If a dRVVT or MRVVT test is prolonged and does not correct when mixed with normal pooled plasma, but does correct with the addition of phospholipids then it is likely that a phospholipid antibody is present.
• If a Thrombin Time test is normal then there is not significant heparin contamination in the blood sample.
• If a Fibrinogen test is normal then it is likely that there is sufficient fibrinogen for normal clot formation.

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

• Platelet Neutralisation (this uses platelets as a source of phospholipids)
• Hexagonal (II) Phase Phospholipid Assay (Staclot-LA test)
• Kaolin Clot Time
• Silica Clotting Time
• Tissue thromboplastin inhibition test
• VDRL or RPR – these are tests for syphilis. Their reagents are made of cardiolipin and they will give a false positive result for both anticardiolipin antibodies and for lupus antibodies
• Coagulation Factors (these may be ordered to rule out factor deficiencies that may cause a prolonged aPTT and bleeding episodes)
• Prothrombin Time (PT)

Other tests that may be run in addition to lupus anticoagulant testing:

• Anticardiolipin and anti-beta2-glycoprotein-1 antibodies to check for antiphospholipid syndrome.
• Platelet count. Mild to moderate thrombocytopaenia is often seen along with the lupus anticoagulant and may be caused by anticoagulant (heparin) therapy.

Patients on heparin or heparin substitute (such as hirudin, danaparoid, or argatroban) or Direct Oral Anticoagulants (DOAC's) anticoagulation therapy may give false-positive results for lupus antibodies but those on warfarin (coumadin) anticoagulant therapy should not. If possible, lupus anticoagulant testing should be done prior to the start of anticoagulation therapy. If a patient with a thrombosis has a lupus anticoagulant it may be necessary to prolong, and possibly increase the intensity of their anticoagulation therapy.

In addition to testing for lupus antibodies, it may sometimes be necessary to test for coagulation factor VIII levels. Coagulation factor VIII inhibitors (specific antibodies against factor VIII) can decrease factor VIII levels and cause false-positive lupus anticoagulant tests. Elevated factor VIII levels, as may be seen in an acute infection or with replacement therapy when someone has Haemophilia A, may shorten the aPTT time, leading to a temporary false negative test for lupus anticoagulant.

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 (liquid part) for testing. There must be the proper amount of blood in the tube and it cannot be clotted or haemolysed. When the blood is centrifuged most of the platelets are left behind. If there are too many in the plasma sample, it may be compromised (because platelets are a source of phospholipids). Also, if the patient's haematocrit (the amount of solid components in their blood) is elevated or decreased test results may be affected. If samples are not tested the same day as receipt the patient’s platelet poor plasma should be frozen within 4 hours and freeze thawing of samples should be avoided as spurious results can occur.