Antiphospholipid Antibodies

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Antiphospholipid Antibodies

What are antibodies?

Antibodies are proteins in the blood that the body produces to fight off foreign agents. Antibodies do this by creating an immunity against unfamiliar microorganisms.


What are autoantibodies?

Autoantibodies are antibodies that are directed against one's self.


What are antiphospholipid antibodies?

Antiphospholipid antibodies interfere with the normal function of blood vessels. They typically cause two kinds of problems:

narrowing and irregularity of the blood vessels (vasculopathy)
blood clots in the blood vessel (thrombosis).
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. These blood vessel problems can then lead to complications such as stroke, heart attack, and miscarriage.

There are several kinds of antiphospholipid antibodies. The two most commonly measured kinds are:

lupus anticoagulant
anticardiolipin antibody
Lupus anticoagulant and anticardiolipin antibody are closely related, but are not the same antibody. This means that a person can have one and not the other. For example, in various studies, 8 percent to 65 percent of people with lupus have the lupus anticoagulant, and 25 percent to 61 percent have anticardiolipin antibody. These antibodies can also be found in people who do not have lupus.

There are other antiphospholipid antibodies, but they are not routinely measured. These include:

anti-beta 2 glycoprotein 1
anti-prothrombin
the "false-positive" test for syphilis
How common are antiphospholipid antibodies?

Like other autoantibodies in systemic lupus, 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.

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 both the lupus anticoagulant and anticardiolipin antibody is increased in lupus patients who have had thrombotic (blood clotting) complications. In addition, studies suggest that the presence of these antibodies may also increase the future risk of such problems. These complications would be:

deep venous thrombosis (thrombophlebitis)
stroke
gangrene
heart attack
The Antiphospholipid Antibody Syndrome, or APLS

Anticardiolipin antibody has been found to be increased in pregnant women with lupus who have had miscarriages. The combination of thrombotic problems, miscarriages, and a low platelet count has been called the Antiphospholipid Antibody Syndrome. 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?


1. Lupus Anticoagulant

Specialized blood tests called coagulation tests measure blood clotting and are used to find the lupus anticoagulant. If the number of seconds that it takes the blood to clot is longer than usual, the physician will suspect that the 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.

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)
kaolin clotting time (KCT)
2. Anticardiolipin Antibody

There are many classes of anticardiolipin antibody, abbreviated as 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 anticardiolipin antibody is measured in an ELISA test. The IgG type of anticardiolipin antibody is the type most often associated with complications.


Sometimes, there are technical difficulties with the IgM test, which makes it more difficult to interpret the results. Some lupus patients with very high IgM anticardiolipin antibody have a problem called 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?

If a person has the lupus anticoagulant or anticardiolipin antibody, but has never had a thrombotic complication, treatment is not currently recommended. However, it is always a good idea to reduce other risk factors for clotting, such as being overweight or smoking.

Some physicians may ask people with antiphospholipid antibodies to take a drug that blocks platelet action, such as low-dose aspirin or ticlopidine. Also, research studies suggest that the antimalarial drug called 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, 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 thrombosis (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 of these people had a second episode of thrombosis 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 episodes of thrombosis.


~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 may be advised. However, if the woman has had miscarriages in the past, several different treatment regimens are available. These include:

aspirin
prednisone
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 treatment of pregnant women with antiphospholipid antibodies to prevent a possible miscarriage is not well understood. Some women are helped by combinations of aspirin, prednisone, and/or Heparin injections, whereas others continue to have miscarriages even with these medications. Prednisone is more likely than subcutaneous Heparin to cause diabetes and an increase in blood pressure during pregnancy. Other treatments, including plasmapheresis or intravenous gammaglobulin, may be considered in individual cases.