Antiphospholipid Antibodies: Anticardiolipin Antibodies, Anti-Beta2 Glycoprotein 1 and the Lupus Anticoagulant
What are antiphospholipid antibodies?
Antibodies are proteins in the blood that the body produces to fight off foreign agents. Antibodies do this by creating immunity against unfamiliar microorganisms. Autoantibodies are antibodies that are directed against one’s self.
Antiphospholipid antibodies interfere with the normal function of blood vessels, causing narrowing and irregularity of the vessel (vasculopathy), and by causing blood clots in the vessel (thrombosis). These blood vessel problems can then lead to complications such as stroke, heart attack, and miscarriage.
There are several kinds of antiphospholipid antibodies. The three most widely measured are lupus anticoagulant, anticardiolipin antibody, and anti-β2 (beta-2) glycoprotein I (one). These antibodies react with proteins in the blood that are bound to phospholipid, a type of fat molecule that is part of the normal cell membrane. Lupus anticoagulant, anticardiolipin antibody and anti-β2 glycoprotein I are closely related, but are not the same antibody. This means that a person can have one and not the others.
There are other antiphospholipid antibodies, but they are not routinely measured. These include anti-prothrombin, anti-phosphatidylserine, and anti-annexin.
How common are antiphospholipid antibodies?
Like other autoantibodies in lupus, the antiphospholipid antibodies can come and go in an individual. There are many ways to measure these antibodies, and different methods may not always give the same result. For example, in various studies, 8-65 percent of people with lupus have lupus anticoagulant, and 25-61 percent have anticardiolipin antibody.
These antibodies can also be found in people who do not have lupus. For example, 2 percent of young women have anticardiolipin antibody. These antibodies were first discovered in people who have lupus, but it is not necessary to have lupus to have these antibodies. In fact, in most studies, more than 50 percent of people with these antibodies do not have lupus. We do not yet understand why a person’s immune system begins to manufacture these antibodies.
Why are antiphospholipid antibodies important?
The presence of lupus anticoagulant, anticardiolipin antibody, and anti-β2 glycoprotein I is increased in people with lupus who have had thrombotic (blood clotting) complications, such as deep venous thrombosis (thrombophlebitis), stroke, gangrene, and heart attack. Studies suggest that the presence of these antibodies may also increase the future risk of such problems.
Antiphospholipid antibodies have been found to be increased in pregnant women with or without lupus who have had miscarriages. The combination of thrombotic problems, miscarriages, and/or a low platelet count has been called the “antiphospholipid antibody syndrome (APS).” It is not necessary to have lupus to have the antiphospholipid antibody syndrome. It is important for doctors to realize this and to check people who have had a stroke, heart attack, or miscarriage for no known reason, to see if they have these antibodies.
How do doctors test for antiphospholipid antibodies?
Specialized blood tests which measure blood clotting (coagulation tests) are used to find lupus anticoagulant. The activated partial thromboplastin time (aPTT) is a widely available blood clotting test that is often used. If the aPTT is normal, more sensitive coagulation tests should be done, which include modified Russell viper venom time (RVVT), platelet neutralization procedure (PNP), and kaolin clotting time (KCT). If the number of seconds that it takes the blood to clot is prolonged, the physician will suspect that lupus anticoagulant is present. This can be confusing, because even though the blood takes longer to clot in the test tube, the blood actually clots more easily in the person’s body.
Anticardiolipin Antibody and Anti-Β2 Glycoprotein I
Anticardiolipin antibody and anti-β2 glycoprotein I are measured in an ELISA test. There are several classes of anticardiolipin antibody—IgG, IgM, and IgA. It is possible to test for all of these antibody classes at once, or the physician may wish to test for each one separately. The IgG and IgA types of anticardiolipin antibody and anti-beta2 glycoprotein are most often associated with thrombotic complications. Some people with lupus who have very high levels of IgM anticardiolipin antibody will develop "hemolytic anemia," in which their immune system attacks their red blood cells.
Since antiphospholipid antibodies can come and go, how often should doctors check for them in people with lupus?
There are no current recommendations on the timing of repeat tests. Certainly the antiphospholipid antibodies should be checked in people who have had thrombotic problems, miscarriages, or low platelet counts.
What is the treatment for a person who has antiphospholipid antibodies or anti-β2 glycoprotein I?
If a person has lupus anticoagulant, anticardiolipin antibody, or anti-β2 glycoprotein I but has never had a thrombotic complication, some doctors will prescribe a daily baby (81 mg) aspirin tablet. However, it is always a good idea to reduce other risk factors for clotting, such as being overweight or smoking. Oral contraceptives and hormone replacement therapy should be avoided. Also, research studies suggest that the antimalarial drug hydroxychloroquine (Plaquenil®) may play a protective role against thrombosis.
If a person has had a thrombotic complication and has these antibodies, treatment may depend on where the clot occurred. In general, after a blood clot (thrombus) has occurred, treatment consists of “thinning” the blood to prevent future clots. This is usually done using warfarin (Coumadin), with aspirin sometimes added.
How successful is treatment for people who have had a thrombus (clot) in association with these antibodies?
Some individuals who had initially been treated with aspirin have had a second episode of thrombosis and have then been treated with warfarin. A few have had a second episode of thrombosis even while on warfarin; however, treatment with warfarin appears to be successful overall. The length of time that this treatment is necessary is unclear. Many physicians recommend long-term or even lifelong treatment to prevent future blood-clotting episodes.
If a woman has antiphospholipid antibodies and is pregnant, what is her treatment?
If the woman has antiphospholipid antibodies and is pregnant for the first time, or has had normal pregnancies in the past, no treatment or a daily baby (81 mg) aspirin may be advised. However, if the woman has had miscarriages in the past, several different treatment regimens are available, including adult-strength aspirin and/or subcutaneous shots of a blood thinner called Heparin. The most commonly used regimen combines Heparin injections and low-dose aspirin. Pregnancies in women with antiphospholipid antibodies are considered to be “high risk pregnancies.”
It is necessary for the obstetrician/gynecologist to work closely with the rheumatologist or other physician who evaluates a woman with miscarriages for antiphospholipid antibodies. Miscarriages, especially early in pregnancy, are not rare, but women who have had multiple miscarriages should be checked for antiphospholipid antibodies as part of an overall obstetric evaluation for causes of miscarriage.
How successful is treatment in women with lupus who have had a miscarriage in association with these antibodies?
The best treatment for pregnant women with antiphospholipid antibodies to prevent a possible miscarriage is not completely understood. As stated above, some women are helped by combinations of aspirin and/or Heparin injections, whereas others continue to have miscarriages even with these medications. Treatment with a glucocorticoid, such as Prednisone, is more likely than subcutaneous Heparin to cause diabetes and an increase in blood pressure during pregnancy, and is usually avoided. Other treatments, including plasmapheresis or intravenous gammaglobulin, may be considered in individual cases.
Thanks to Michelle Petri, M.D., M.P.H., Professor of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, for this information.
Last medical review 3-25-2013