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Last updated:
November 14, 2016
Years published: 1994, 1995, 1996, 2001, 2002, 2007, 2011, 2016
NORD gratefully acknowledges Robert A. S. Roubey, MD, Adjunct Professor of Medicine, Division of Rheumatology, Allergy and Immunology, Dept. of Medicine and Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, for assistance in the preparation of this report.
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 person to person 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, also known as CAPS or Asherson’s syndrome, is an extremely rare variant of APS in which multiple blood clots affect various organ systems of the body potentially causing life-threatening multi-organ failure. The specific presentation, progression and organs involved vary from person to person. 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 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. 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 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.
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.
The most common blood tests used to detect antiphospholipid antibodies are anticardiolipin antibody immunoassays (which, despite the name, detect mainly antibodies to beta-2-glycoprotein I), anti-beta-2-glycoprotein antibody immunoassays, and lupus anticoagulant tests (coagulation assays that detect subsets of anti-beta-2-glycoprotein I antibodies and anti-prothrombin antibodies). 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.
Treatment
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.
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). New oral blood thinners (dabigatran, rivaroxaban, and apixaban) have recently been approved to treat other blood clotting conditions. Studies are needed to determine whether these drugs are appropriate for preventing recurrent blood clots in patients with APS. Individuals with repeated thrombotic events may require lifelong anticoagulant therapy.
Importantly, affected individuals are strongly encouraged to avoid or reduce 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. 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.
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.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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For information about clinical trials sponsored by private sources, contact:
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TEXTBOOKS
Hogan WJ, Nichols WL. Antiphospholipid Syndrome. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:2.
Rand JH, Wolgast L. “The Antiphospholipid Syndrome” in Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri M. Eds. Williams Hematology. 9th ed. McGraw-Hill Companies. New York, NY; 2016:2233-2252.
JOURNAL ARTICLES
Andreoli L, Bertsias GK, Agmon-Levin N, et al. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2016 Jul 25. pii: annrheumdis-2016-209770. doi: 10.1136/annrheumdis-2016-209770. [Epub ahead of print]; https://www.ncbi.nlm.nih.gov/pubmed/27457513
Rodríguez-Pintó I, Moitinho M, Santacreu I, Shoenfeld Y, Erkan D, Espinosa G, Cervera R. CAPS Registry Project Group (European Forum on Antiphospholipid Antibodies). Catastrophic antiphospholipid syndrome (CAPS): Descriptive analysis of 500 patients from the International CAPS Registry. Autoimmun Rev. 2016 Sep 15. pii: S1568-9972(16)30205-1. doi: 10.1016/j.autrev.2016.09.010. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27639837
Chaturvedi S, McCrae KR. The antiphospholipid syndrome: still an enigma. Hematology Am Soc Hematol Educ Program. 2015;2015:53-60.
Chighizola CB, Raschi E, Borghi MO, Meroni PL. Update on the pathogenesis and treatment of the antiphospholipid syndrome. Curr Opin Rheumatol. 2015; 27:476-482.
Krilis SA, Giannakopoulos B. Laboratory methods to detect antiphospholipid antibodies. Hematology Am Soc Hematol Educ Program 2014:321-328.
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/