NORD is very grateful to Robert A. S. Roubey, MD, Associate Professor of Medicine, Division of Rheumatology, Allergy and Immunology, Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, for assistance in the preparation of this report.
Synonyms of Antiphospholipid Syndrome
- antiphospholipid antibody syndrome
- Hughes syndrome
- lupus anticoagulant syndrome
- primary antiphospholipid syndrome
- catastrophic antiphospholipid syndrome (Asherson's syndrome)
Antiphospholipid syndrome (APS) is a rare autoimmune disorder characterized by recurring blood clots (thromboses). Blood clots can form in any blood vessel of the body. The specific symptoms and severity of APS vary greatly from case to case depending upon the exact location of a blood clot and the organ system affected. APS may occur as an isolated disorder (primary antiphospholipid syndrome) or may occur along with another autoimmune disorder such as systemic lupus erythematosus (secondary antiphospholipid syndrome).
APS is characterized by the presence of antiphospholipid antibodies in the body. Antibodies are specialized proteins produced by the body's immune system to fight infection. In individuals with APS, certain antibodies mistakenly attack healthy tissue. In APS, antibodies mistakenly attack certain proteins that bind to phospholipids, which are fat molecules that are involved in the proper function of cell membranes. Phospholipids are found throughout the body. The reason these antibodies attack these proteins and the process by which they cause blood clots to form is not known.
The specific symptoms associated with antiphospholipid syndrome are related to the presence and location of blood clots. Blood clots can form in any blood vessel of the body. Clots are twice as likely to form in vessels that carry blood to the heart (veins) as in vessels that carry blood away from the heart (arteries). Any organ system of the body can become involved. The lower limbs, lungs and brain are affected most often. APS also causes significant complications during pregnancy.
The severity of APS varies, ranging from minor blood clots that cause few problems to an extremely rare form (catastrophic APS) in which multiple clots form throughout the body. However, in most cases, blood clots will only develop at one site.
When blood clots affect the flow of blood to the brain a variety of issues can development including serious complications such as stroke or stroke-like episodes known as transient ischemic attacks. Less frequently, seizures or unusual shaking or involuntary muscle movements (chorea) may occur.
Blood clots in large, deep veins are referred to as deep vein thrombosis (DVT). The most common site of DVT is the legs, which can become painful and swollen. In some cases, a piece of the blood clot may break off, travel in the bloodstream, and become lodged in the lungs. This is referred to as pulmonary embolism. Pulmonary embolism may cause breathlessness, a sudden pain the chest, exhaustion, high blood pressure of the pulmonary arteries, or sudden death.
Skin rashes and other skin diseases may occur in people with APS. These include blotchy reddish patches of discolored skin, a condition known as livedo reticularis. In some cases, sores (ulcers) may form on the legs. Lack of blood flow to the extremities can cause loss of living tissue (necrotic gangrene), especially in the fingers or toes.
Additional abnormalities that may occur in individuals with APS include clot-like deposits on the valves of the heart (valvular heart disease) which can permanently damage the valves. For example, a potential complication is mitral valve regurgitation (MVR). In MVR, the mitral valve does not shut properly allowing blood to flow backward into the heart. Affected individuals may also experience chest pain (angina) and the possibility of a heart attack (myocardial infarction) at an early age but these problems are not thought to be related to valvular heart disease.
Some affected individuals can develop low levels of blood platelets (thrombocytopenia). Thrombocytopenia associated with antiphospholipid antibodies is usually mild and only rarely causes easy or excessive bruising and prolong bleeding episodes. Affected individuals are also at risk for autoimmune hemolytic anemia, a condition characterized by the premature destruction of red blood cells by the immune system.
Some individuals have reported symptoms that resemble multiple sclerosis including numbness or a sensation of pins and needles, vision abnormalities such as double vision, and difficulty walking, but it is not known if these problems are related to APS. Some data show an association of APS with cognitive dysfunction, but the mechanism is not known.
In women, APS can cause complications during pregnancy including repeated miscarriages, fetal growth delays (intrauterine growth retardation), and preeclampsia. Preeclampsia is a condition characterized by high blood pressure, swelling and protein in the urine. Symptoms associated with preeclampsia vary greatly, but may include headaches, changes in vision, abdominal pain, nausea and vomiting.
CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME (CAPS)
Catastrophic antiphospholipid syndrome is an extremely rare variant of APS in which multiple blood clots affect various organ systems of the body potentially causing life-threatening multiorgan failure. The specific presentation, progression and organs involved vary from case to case. CAPS may develop in a person with primary or secondary APS or in individuals without a previous diagnosis of APS. In some cases, infection, trauma, or surgery appears to trigger the condition.
Antiphospholipid syndrome is an autoimmune disorder of unknown cause. Autoimmune disorders are caused when the body natural defenses (antibodies, lymphocytes, etc.) against invading organisms suddenly begin to attack perfectly healthy tissue. Researchers believe that multiple factors including genetic and environmental factors play a role in the development of APS. In rare cases, APS has run in families suggesting that a genetic predisposition to developing the disorder may exist.
The antibodies that are present in APS are known as antiphospholipid antibodies. There are several different types of antiphospholipid antibodies. In APS, two types are most prevalent - lupus anticoagulant and anticardiolipin antibodies. These antibodies were originally thought to attack phospholipids, fatty molecules that are a normal part of cell membranes found throughout the body. However, researchers now know that these antibodies mostly target certain blood proteins that bind to phospholipids. The two most common proteins affected are beta-2-glycoprotein I and prothrombin. The exact mechanism by which these antiphospholipid antibodies eventually lead to the development of blood clots is not known.
APS may occur in patients with another autoimmune disorder, most commonly lupus. These cases are referred to as secondary APS.
APS affects males and females, but a large percentage of primary APS patients are women with recurrent pregnancy loss. Some estimates suggest that 1 in 5 cases of recurrent miscarriages or deep vein thromboses are due to APS. As many as one-third of cases of stroke in people under 50 years of age may be due to APS. Secondary APS occurs mainly in lupus, and about 90% of lupus patients are female.
Symptoms of the following disorders can be similar to those of antiphospholipid syndrome. Comparisons may be useful for a differential diagnosis.
Several rare genetic disorders are characterized by the formation of blood clots (thromboses). These disorders may be collectively referred as the thrombophilias and include protein C deficiency, protein S deficiency, antithrombin III deficiency, and factor V Leiden. (For more information on these disorders, contact the National Alliance for Thrombosis and Thrombophilia.)
Some individuals with APS may be misdiagnosed as having multiple sclerosis (MS) because of the development of similar neurological symptoms. Multiple sclerosis is a chronic disease of the brain and spinal cord (central nervous system) that may be progressive, relapsing and remitting, or stable. The pathology of MS consists of small lesions called plaques that may form randomly throughout the brain and spinal cord. These patches prevent proper transmission of nervous system signals and thus result in a variety of symptoms including eye abnormalities, impairment of speech, and numbness or tingling sensation in the limbs and difficulty walking. The exact cause of multiple sclerosis is unknown. (For more information on this disorder choose "Multiple Sclerosis" as your search term in the Rare Disease Database.)
Lupus (systemic lupus erythematosus) is a chronic, inflammatory autoimmune disorder that can affect various organ systems. In autoimmune disorders, the body's own immune system mistakenly attacks healthy cells and tissues causing inflammation and malfunction of various organ systems. In lupus, the organ systems most often involved include the skin, kidneys, blood and joints. Many different symptoms are associated with lupus, and most affected individuals do not experience all of the symptoms. The initial symptoms may include arthritis, skin rashes, fatigue, fever, pleurisy, and weight loss. In some cases, lupus may be a mild disorder affecting only a few organ systems. In other cases, it may result in serious complications. (For more information on this disorder, choose "Lupus" as your search term in the Rare Disease Database.)
A diagnosis of antiphospholipid syndrome is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic physical findings (at least one blood clot or clinical finding), and a variety of tests including simple blood tests.
Specialized blood tests called a coagulation tests are used to measure blood clotting and can indicate the presence of lupus anticoagulant in the blood. Enzyme-Linked ImmunoSorbent Assays (ELISAs) can detect the presence of anticardiolipin and anti-beta-2-glycoprotein I antibodies in the blood. Positive tests should be repeated because antiphospholipid antibodies can be present in short intervals (transiently) due to other reasons such as infection or drug use. Borderline negative tests may need to be repeated because individuals with APS have initially tested negative for the antiphospholipid antibodies.
Individuals with APS who do not have symptoms may not require treatment. Some individuals may undergo preventative (prophylaxis) therapy to avoid blood clots from forming. For many individuals, daily treatment with aspirin (which thin the bloods and prevents blood clots) may be all that is needed.
Affected individuals are also encouraged to avoid risk factors that increase the risk of a blood clot forming. Such risks include smoking, the use of oral contraceptives, high blood pressure (hypertension), or diabetes. Individuals with repeated thrombotic events may require lifelong anticoagulant therapy.
Individuals with a history of thrombosis may be treated with drugs that preventing clotting by thinning the blood. These drugs are often referred to as anticoagulants and may include heparin and warfarin (Coumadin).
During pregnancy, women at a high risk for pregnancy loss are treated with heparin, sometimes in combination with low dose aspirin.
In some cases, heart valve damage may be severe and require surgical replacement.
A national registry and tissue repository called the Antiphospholipid Syndrome Collaborative Registry (APSCORE) has been established by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Center on Minority Health and Health Disparities (NCMHD). Biomedical researchers at eight medical centers collected clinical, demographic and laboratory information from patients and make it available to researchers and medical practitioners. For information, contact:
Robert A. S. Roubey, MD
Associate Professor of Medicine
Division of Rheumatology and Immunology, CB #7280
Thurston Building, Room 3330
University of North Carolina
Chapel Hill, NC 27599-7280
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
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Antiphospholipid Syndrome Resources
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Lichtman MA, Beutler E, Kipps TJ, Selisohn U, et al. Eds. Williams Hematology. 7th ed. McGraw-Hill Companies. New York, NY; 2006:2009-29.
Hanly JG. Antiphospholipid Syndrome: an overview. CMAJ. 2003;168:1675-82.
Derkson RHWM, de Groot PG. Clinical consequences of antiphospholipid antibodies. Neth J Med. 2004;62:273-8.
Lim W, Crowther MA, Eikelboom JW. Management of antiphospholipid antibody syndrome. A systemic review. JAMA. 2006;295:1050-7.
Kamat AV, D'Cruz DP, Hunt BJ. Managing antiphospholipid syndrome in children. Haematologica. 2006;91:167-80.
Cervera R, Asherson RA, Acevedo ML, et al., Antiphospholipid syndrome associated with infections: clinical and microbiological characteristics of 100 patients. Ann Rheum Dis. 2004;63:1312-7.
Misita CP, Moll S. Antiphospholipid antibodies. Circulation. 2005;112:e39-44.
FROM THE INTERNET
Tektonidou M. Antiphospholipid Syndrome. Orphanet encyclopedia, Updated May 2004 Available at: http://www.orpha.net/data/patho/Pro/en/Antiphospholipid-FRenPro5517.pdf Accessed:November 29, 2011.
Belilos E and Carsons S . Antiphospholipid Syndrome. Emedicine Journal, August 3, 2009. Available at: http://www.emedicine.com/med/topic2923.htm Accessed: November 29, 2011.
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