Antiphospholipid Syndrome (APS) is a disorder characterized by elevated levels of multiple different antibodies that are associated with both arterial and venous thrombosis (clots in the arteries and veins).
What is antiphospholipid syndrome (APS)?
Antiphospholipid syndrome (APS), also known as antiphospholipid antibody syndrome and sometimes Hughes syndrome, is a disorder characterized by elevated levels of multiple different antibodies (proteins produced by the body to fight off foreign substances) that are associated with both arterial and venous thrombosis (clots in the arteries and veins).
There are two primary classes of antiphospholipid (aPL) antibodies, the antibodies associated with APS. These are called anticardiolipin antibodies and the lupus anticoagulant, and are directed against specific molecules. These aPL antibodies appear to be mainly directed against two particular molecules: beta-2-glycoprotein I (ß2GPI, a normal protein found in the blood whose function is unknown) and another molecule known as prothrombin (a normal blood protein that binds to phospholipids and plays a very important role in blood clotting).
These aPL antibodies were first noted in a group of people who had positive tests for syphilis without signs of infection. It was then noticed that some individuals who continued to have false-positive tests for syphilis went on to develop systemic lupus erythematosus (SLE) and other similar conditions. Later studies found a protein called the lupus anticoagulant in a number of individuals with SLE. A case report in 1956 described an individual with recurrent pregnancy loss, thrombophlebitis (inflammation of a vein related to a blood clot) and lupus anticoagulant. The work of Dr. Graham Hughes and his colleagues in the 1980s provided further understanding of APS, including the introduction of testing for anticardiolipin antibodies.
Up until the 1980s, it was thought that aPL antibodies were directed against a type of molecule known as anionoic phospholipids. However, in the early 1990s, several different groups discovered that this was not the case. Anticardiolipin antibodies were found to act against ß2GPI, while the lupus anticoagulant was first found to act against ß2GPI and, more recently, prothrombin.
There are two main classifications of APS. If the individual has no known underlying autoimmune disorder, the person is said to have primary APS. If the individual has SLE or another underlying autoimmune disorder, the person is said to have secondary APS. Although APS is divided into these two categories, research indicates that there is little essential difference between them.
Signs, complications and conditions
APS usually shows up for the first time as vascular thrombosis (a blood clot in an artery or vein) or embolism (the blockage of a blood vessel caused by a clot that has moved in the blood stream from the site where it formed to a different place in the body) or as recurrent pregnancy loss. Thrombocytopenia (a low platelet count), certain skin problems, neurological signs, heart valve disease and certain autoimmune diseases have also been noted in association with APS. Pulmonary hypertension (high blood pressure in the arteries that supply the lungs) and sensorineural hearing loss (hearing loss caused by damage to the inner ear or to the nerve pathways from the inner ear) have been noted in some individuals with APS as well.
A diagnosis of APS is made based on both clinical and laboratory findings. APS is diagnosed if an individual experiences one or more episodes of thrombosis or pregnancy loss and if aPL antibodies are detected through laboratory testing of the individual’s blood.
There are two main types of antiphospholipid antibody tests – immunological tests, like the anticardiolipin ELISA (enzyme-linked immunoassay), and coagulation-based tests for the lupus anticoagulant. ELISAs are immunologically-based tests, or immunoassays, in which an antigen-antibody reaction is used to detect the antibodies. In contrast, lupus anticoagulant tests detect antibodies based on their ability to slow down phospholipid-dependent clotting reactions. Most individuals with APS have antibodies that can be detected in both tests; however, a significant percentage of patients are positive in one test but not the other. Therefore, to diagnose APS, it is standard practice for both tests to be performed. The tests are then repeated six to eight weeks later to confirm the presence of aPL antibodies.
There are no hard and fast statistics about the number of people with aPL antibodies or APS. What we know is based on estimates from different studies over time. Research suggests that aPL antibodies may be found in around 1 to 5 percent of the healthy general population. Primary APS accounts for over 50% of cases. In individuals with SLE, approximately 30 percent have aPL antibodies, and around 30-50 percent of these individuals have symptoms and signs of APS. It is more difficult to measure the number of people with primary APS, but studies indicate that between 5-30 percent of individuals with thrombosis and no history of SLE have aPL antibodies. Additional studies suggest that aPL antibodies may play a role in approximately one-third of strokes in individuals under the age of 50.
A female predominance has been noted, especially for secondary APS. This parallels the association of APS with SLE and other connective-tissue diseases, which also have a female predominance.
If thrombosis occurs in an individual with APS, this usually happens between the ages of 35-45 years. After age 60, signs and symptoms of are APS rarely seen for the first time.
Treatment for APS must be individualized according to the person’s current health status and the types of problems that person has experienced due to their APS. In general, for a person who has aPL antibodies and has had a thrombotic event, a short-term course of heparin (an anticoagulant, which is a type of medication used to prevent blood clots from forming or getting bigger) is followed by long-term – sometimes life-long – treatment with warfarin (another type of anticoagulant).
In women with moderate to high levels of aPL antibodies and a history of pregnancy loss who wish to get pregnant again, treatment is again individualized. After consulting with and obstetrician and rheumatologist and/or hematologist, women generally begin treatment with heparin and low-dose aspirin.
For those individuals who have been found to have aPL antibodies but have not had any signs or symptoms of APS, low-dose aspirin is generally recommended by their doctors.
If you or someone you know has been diagnosed with APS, we recommend talking with a health care provider to determine a personalized course of management.
Although APS has been reported to occur in multiple members of the same family, no clear inheritance pattern has been identified and no gene has been found to be the sole cause of this condition. One report in 1999 studied families with more than one affected member, examined possible modes of inheritance, and examined links with certain genes. In seven families, 30 out of 101 family members met diagnostic criteria for the syndrome. The data were fitted best by either a dominant (one copy of the altered gene inherited from one parent causes the condition) or codominant (features related to the condition from both parents are observed) model.