This is also known as anticardiolipin antibody syndrome or lupus anticoagulant syndrome. This syndrome is characterized by an increased risk of venous or arterial blood clots (thrombosis), recurrent mid- to late-pregnancy loss, and thrombocytopenia in individuals who have antibodies to phospholipids.

The antiphospholipid antibody syndrome may be primary, when it occurs alone, or secondary, when it is found in association with another autoimmune disease. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) is the most common cause of secondary antiphospholipid antibody syndrome, but less common causes are RHEUMATOID ARTHRITIS, SCLERODERMA,and SJÖGREN’S SYNDROME.

Antiphospholipid antibodies were first recognized as causing a false-positive test result in early blood tests for syphilis. These antibodies do not always result in complications. When complications such as thrombosis do occur in patients who have the antibodies, they are diagnosed with antiphospholipid antibody syndrome.

Approximately 3 percent of healthy people have antiphospholipid antibodies, but many never develop the antiphospholipid antibody syndrome. Treatment with some drugs, for example chlorpromazine, quinidine, and hydralazine, can induce antiphospholipid antibodies.

These drug-induced antiphospholipid antibodies, and those found in association with HIV infection, are seldom associated with thrombosis. The term lupus anticoagulant was coined when it was recognized that some patients with SLE had antibodies that acted as anticoagulants in the laboratory by prolonging tests of blood clotting such as the Russell viper venom time or activated partial thromboplastin time.

However, the term lupus anticoagulant turned out to be a misnomer. The anticoagulant effects occur only in the test tube. These patients in fact have an increased risk of blood clots, rather than excessive bleeding that would be expected if the antibody acted as an anticoagulant.

It was also a misnomer because many people who had a positive lupus anticoagulant test did not have lupus. The antiphospholipid antibody syndrome and the lupus anticoagulant syndrome are now known to be related, and some patients who have an antiphospholipid antibody also have a positive lupus anticoagulant test.

However, the overlap is not complete, and sometimes one test is positive and the other negative. Both tests are associated with an increased risk of thrombosis. In addition to antiphospholipid antibodies, it is now known that other antibodies, for example beta2- glycoprotein antibodies, play an important role in the development of the syndrome.

Cause - It is not clear how antiphospholipid antibodies that decrease blood clotting in laboratory tests increase clotting in people. Several theories have been proposed. Normal endothelium (the thin layer of cells lining the inside of blood vessels) has complex protective mechanisms to prevent thrombosis (i.e., has an anticoagulant effect).

Many of the antibodies found in this syndrome in fact bind to beta2-glycoprotein I and prothrombin. Beta2-glycoprotein I and prothrombin are proteins that bind to phospholipids on cell walls in the process of thrombus formation. One popular theory of how the antiphospholipid syndrome occurs is that the antibodies interfere with these mechanisms and thereby allow thrombosis to occur.

The underlying trigger that results in the formation of antiphospholipid antibodies is not known. Indeed, the presence of the antiphospholipid syndrome simply seems to tip the body’s normal balance between thrombosis and anticoagulation in favor of thrombosis. A relatively minor event can then cause damaging thrombosis.

Symptoms - Most individuals with antiphospholipid antibodies do not have symptoms unless a complication occurs. A thin, lacy, red-purple rash, LIVEDO RETICULARIS, is common but does not cause symptoms. Patients with associated diseases such as SLE will have the usual symptoms of that disease.

Pregnancy loss A common complication is repeated miscarriage, often occurring in the second half of pregnancy. Up to 50 percent of women with high levels of IgG antiphospholipid antibodies will have some pregnancy loss. Lower levels and IgM or IgA antibodies are associated with a lower rate of complications.

Overall, the antiphospholipid syndrome is not a common cause of pregnancy loss. Pregnancies that do not end in miscarriage have a greater chance of delivering prematurely, thereby placing the immature infant at risk. In pregnancies that carry on to term, fetal growth is often poor because the placenta does not function well and the supply of nutrients to the unborn baby is inadequate.

Thrombosis - The antiphospholipid antibody syndrome is often diagnosed when someone spontaneously develops blood clots in his or her arteries or veins. Deep vein thrombosis (DVT) most often occurs in the veins of the legs but can occur anywhere. This can be dangerous if the clot breaks off and lodges in the blood vessels of the lungs (pulmonary embolus) since this is sometimes fatal.

Arterial thrombosis reduces blood supply to the organ affected and can result in stroke, myocardial infarction (heart attack), or gangrene of a limb. As with other complications, the antiphospholipid syndrome is not a common cause of these vascular problems. It should be suspected when thromboses occur in young patients, nonsmokers, or in unusual sites.

Other complications - These include leg ulcers, heart valve irregularities known as vegetations, and nervous system complications such as stroke. Thrombocytopenia is common but is usually mild and seldom leads to complications such as bleeding. Catastrophic antiphospholipid antibody syndrome is rare but often fatal. It was given this name because in addition to clots occluding the blood supply to limbs, several organs such the lungs, kidneys, and brain are affected.

Diagnosis - The diagnosis of antiphospholipid antibody syndrome is difficult and requires a high index of suspicion. Recurrent thromboses, thrombosis in a person for no apparent reason, or recurrent midtrimester abortions usually trigger diagnostic testing. The tests performed include tests for both anticardiolipin antibodies and lupus anticoagulant.

Because the antiphospholipid syndrome is so common in patients with SLE, lupus patients are often screened to assess their risk of thrombosis. Antiphospholipid antibodies can cross-react with the antibodies detected by some blood tests for syphilis, resulting in a false-positive test for that disease.

Most patients with significant levels of antiphospholipid antibodies who have not had a complication take low-dose aspirin to decrease their chances of developing a clot. Patients who have had a thrombosis are very likely to have further problems. Most patients with the antiphospholipid antibody syndrome who have had one thrombosis are therefore treated with a drug to prevent blood clots forming (anticoagulant).

Warfarin is the usual drug used and this is taken for a long time, sometimes life. The dose of warfarin needs to be taken at the higher end of the usual dose range to be effective. If there is a contraindication to treatment with warfarin, then low-dose aspirin, which prevents platelets from aggregating, is used, but it is not as effective as full anticoagulation with warfarin.

In this situation an injectable anticoagulant (a heparin) can be used for short periods to protect the patient during high-risk periods such as surgery or long flights. Treatment to prevent recurrence of pregnancy loss is not standardized. However, good results are possible using the newer low-molecular weight heparins given as daily or twice daily subcutaneous injections, often with aspirin, during and after pregnancy.

The patient is taught to do this herself at home. Prolonged use of heparins can cause OSTEOPOROSIS, and some protection against this should also be used. High doses of corticosteroids during pregnancy have been tried and are effective, but the side effects outweigh the benefits.