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The Antiphospholipid Syndrome in Children and Adolescents Kaleo Ede, M.D. Fellow in Pediatric Rheumatology Deborah Mccurdy, M.D. Associate Professor of Pediatrics, Mattel Children's Hospital at Ucla Los Angeles, CA WHAT IS THE ANTIPHOSPHOSPHOLID ANTIBODY SYNDROME? The antiphospholipid antibody syndrome (or APS) is a disease in which children and adolescents form blood clots because of abnormal antibodies in their blood. In adults, women with the antiphospholipid antibody syndrome may also have repeated miscarriages associated with the abnormal antibodies. The cause of the disease is unknown. The antiphospholipid antibody syndrome can occur without any other illnesses present in the same person, when it is referred to as primary antiphospholipid syndrome. This disease is rare in children and adolescents. It is more common for children to have other diseases such as systemic lupus erythematosus (or SLE), systemic vasculitis, or juvenile rheumatoid arthritis at the same time as having the antiphospholipid antibody syndrome. In this instance, it is called secondary antiphospholipid antibody syndrome. Antiphsopholipid antibody syndrome has also been seen in rare cases in newborn babies of mothers with antiphospholipid antibodies. WHAT ARE ANTIPHOSPHOLIPID ANTIBODIES? Antibodies are a normal part of our immune system and are usually very useful to recognize and protect us from infections. An antibody, which is an immunoglobulin, is a large protein that circulates in our blood and detects bacteria and viruses and clears them from the blood. What happens when these normally beneficial proteins recognize a part of our body instead of a germ? When this occurs, it is called autoimmune disease (the immune system is directed against one's self) and autoantibodies are produced that bind to normal tissue and cause inflammation and damage. Antiphospholipid antibodies are autoantibodies that bind phospholipids that are special fat molecules that are part of the normal cell membrane and found in the lining of the blood vessels. When the antiphospholipid antibodies bind to the phospholipids, they may cause damage to the blood vessels (vasculopathy) and cause a clot to form in the vessel (thrombosis). This can cause narrowing and irregularity to the blood vessel and if a clot forms the blood not longer flows to the organ. This can lead to problems such as blood clots in the veins of the legs, stroke, heart attacks, and miscarriage. Because there are many types of phospholipids in the various cell membranes of different organs, there are many antiphospholipid antibodies and they are measured in a variety of ways. The two most commonly measured kinds are the lupus anticoagulant and the anticardiolipin antibody. Both are directed against phospholipids, but the cardiolipin antibody was first detected using tissue from the heart and the lupus anticoagulant was found in patients with lupus whose blood took longer then usual to clot in the laboratory. The term lupus anticoagulant is considered a misnomer because, although in the laboratory it takes longer for blood to clot, in the patient it is associated with abnormal clots. A person may have both the lupus anticoagulant and anticardiolipin antibody or only one or the other. detect the antiphospholipid antibodies include the anti-beta 2 glycoprotein 1, anti-prothrombin, the "false-positive" test for syphilis, but these are not always measured. HOW COMMON ARE ANTIPHOSPHOLIPID ANTIBODIES? In various studies, 8 percent to 65 percent of people with lupus have the lupus anticoagulant, and 25 percent to 61 percent have anticardiolipin antibodies. These antibodies can also be found in people who do not have lupus. 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. WHAT ARE THE SYMPTOMS OF ANTIPHOSPHOLIPID ANTIBODY SYNDROME? The most common symptom of antiphospholipid antibody syndrome is blood clots in the legs, referred to as deep venous thrombosis. This can cause a variety of problems in kids including swelling and pain of the involved leg, as well as the potential for the blood clot to travel to the lung, where it is called pulmonary embolism. Blood clots can also form in the arteries, where it can cause problems such as strokes, heart attacks, and visual problems. Other symptoms of antiphospholipid syndrome can include a low platelet count (also known as thrombocytopenia), low red blood cells (or anemia), skin rash (ulcers and livedo reticularis), heart valve problems, and migraine headaches. WHAT ARE THE TESTS 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 the modified Russell viper venom time (RVVT), platelet neutralization procedure (PNP), and the kaolin clotting time (KCT) 2. Anticardiolipin Antibodies There are many classes of anticardiolipin antibody, abbreviated as IgG, IgM, and IgA. The anticardiolipin antibody is measured in an ELISA test. The IgG type of anticardiolipin antibody is the type most often associated with complications. 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. To make the diagnosis of APLS, the antibodies must be present at significant levels twice at least 12 weeks apart. This is because sometimes the antibodies may be positive after an infection, but they do not last for very long. WHAT IS THE TREATMENT FOR A PERSON WHO HAS ANTIPHOSPHOLIPID ANTIBODIES? The blood vessels of children and adolescents are at less risk of clots then adults who may also have hardening of the arteries. Therefore a child who has the lupus anticoagulant or anticardiolipin antibody, but has never had a thrombotic complication, does not require treatment and it is not currently recommended. Some physicians may ask people with antiphospholipid antibodies to take a drug that blocks platelet action, such as low-dose aspirin. 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 heparin initially and subsequently warfarin (Coumadin), with aspirin sometimes added. Occasionally, other forms of blood-thinning medications, including injectable medicines are used. 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. WHAT ABOUT APS AND PREGNANCY? Problems during pregnancy represent another potential complication for females with the antiphospholipid syndrome. There are specific instances in which females who have antiphospholipid antibodies can be diagnosed with APS based only on pregnancy problems. This includes: 1) Three or more consecutive miscarriages when the fetus is less than 10 weeks old; 2) One or more miscarriage(s) when the fetus is 10 weeks old or older; or 3) One or more premature births when the infant is 34 weeks old or younger due to conditions such as eclampsia, severe pre-eclampsia or placental insufficiency. Women who have antiphospholipid antibodies or the antiphospholipid syndrome should be followed during pregnancy by a OB/GYN doctor with high-risk pregnancy experience. HOW ARE FEMALES WITH APS TREATED DURING PREGNANCY? The treatment for pregnant females with antiphospholipid syndrome depends on three specific situations. For female patients who have antiphospholipid antibodies but have not previously had blood clots or problems during pregnancy, they are usually given a low-dose of aspirin throughout the pregnancy and to continue after pregnancy as well. For females who have been diagnosed with APS and have had blood clots in the past, they are treated during pregnancy with "therapeutic" (or high-doses) of blood thinners (either unfractionated heparin or low-molecular weight heparin) given by injection under the skin or through the veins, and then switched back to oral blood thinners (warfarin) after the baby is born. For females who have been diagnosed with APS and have only had problems during pregnancy (no history of blood clots), they are treated during pregnancy with low-dosage aspirin and "prophylactic" (or lower-doses) of blood thinner (either unfractionated heparin or low-molecular weight heparin) given by injection under the skin or through the veins, and then continued on low-dose aspirin for life as well as the injection blood thinner for six months after the baby is born.  |
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