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| DiseaseID |
HGD60 |
| Genetic
Disorder |
Antiphospholipid syndrome
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| Gene
Name |
coagulation factor V (proaccelerin, labile factor) |
| Description |
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.
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| Symptoms |
People with Hughes syndrome are at greater risk of:
Venous thrombosis in the legs (DVT), arms and internal organs (kidney, liver, lung, brain, eye)
Arterial thrombosis, which can lead to recurrent stroke and transient ischaemic attacks (TIAs), headaches and neurological problems, heart attacks
Mild thrombocytopenia (low platelet count in the blood)
Multiple sclerosis-like episodes
Chorea (abnormal movements)
Memory loss
Seizures
Heart valve disease
Skin rash known as livedo reticularis
Recurrent pregnancy loss
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| Causes |
The cause of antiphospholipid syndrome is not completely known. Antiphospholipid antibodies reduce the levels of annexin V, a protein that binds phospholipids and has potent clot-blocking (anticoagulant) activity. The reduction of annexin V levels is thought to be a possible mechanism underlying the increased tendency of blood to clot and the propensity to pregnancy loss characteristic of the antiphospholipid syndrome.
Antiphospholipid antibodies, such as anticardiolipin, have also been associated with decreased levels of prostacyclin, a chemical that prevents the clumping together of normal blood clotting elements called platelets. |
| Diagnosis |
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. For more about the tests used to diagnose APS, go to the Antiphospholipid Syndrome Collaborative Registry (APSCORE).
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| Treatment |
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 |
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