Asherson's Syndrome - Symptoms, Causes, Treatment | NORD (2024)

Disease Overview

Asherson’s syndrome is an extremely rare autoimmune disorder characterized by the development, over a period of hours, days or weeks, of rapidly progressive blood clots affecting multiple organ systems of the body. Conditions such as infections, immunizations, wounds caused due to physical trauma and failure in the anticoagulation mechanism of the body usually act as “triggers”.

The syndrome is particularly common among patients with antiphospholipid syndrome who experience a cessation of the anticoagulation mechanism rleated to recurrent bleeding in the body. It is usually seen in patients who have previously suffered from a simple/classic episode of antiphospholipid syndrome. It is not known why patients of antiphospholipid syndrome often have the tendency to be “catapulted” into a serious or fatal multiorgan failure, while the same triggers in other individuals may only result in recurrent large vessel thrombosis. The symptoms are also aptly observed in patients during pregnancy or in the weeks after childbirth (puerperium) and may follow the HELLP syndrome or be associated with malignancies. Symptoms vary from case to case depending upon the specific organ systems involved. Asherson’s syndrome can rapidly result in life-threatening multiorgan failure.

Asherson’s syndrome is a severe variant of antiphospholipid syndrome (APS), an autoimmune disorder in which blood clots occur in relation to the presence of antiphospholipid antibodies in the body. Antibodies are specialized proteins produced by the body’s immune system to fight infection. In autoimmune disorders, antibodies mistakenly attack healthy tissue. In APS and Asherson’s syndrome, 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.

Asherson’s syndrome may occur in individuals who have primary or secondary APS or in individuals with lupus or other autoimmune disorders. In some cases, no previous history of these disorders may be present. The exact cause of Asherson’s syndrome is unknown.

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Synonyms

• Catastrophic Antiphospholipid Syndrome

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Signs & Symptoms

The symptoms of Asherson’s syndrome are caused by complications resulting from the development of multiple blood clots (thromboses) in the body. Multiple blood clots may form in a matter of hours, days or weeks, potentially causing life-threatening multiorgan failure.

Specific symptoms vary depending upon what organ systems are involved. The kidneys, stomach, lungs, heart, skin and central nervous system are commonly affected. Involvement of the kidneys may result in kidney dysfunction and associated symptoms such as low urine production and high blood pressure (hypertension).

Involvement of the lungs (pulmonary system) may result in adult respiratory distress syndrome, a severe lung disorder characterized by difficulties (dyspnea), excessively deep and rapid breathing (hyperventilation) and insufficient levels of oxygen in the circulating blood (hypoxemia). Additional pulmonary symptoms may include (pulmonary embolism).

Blotchy reddish patches of discolored skin, a condition known as livedo reticularis, bruising, and the loss of living tissue (gangrene) may develop. Central nervous system symptoms may include stroke (cerebral infarction), seizures, and a condition characterized by altered brain structure and function (encephalopathy).

If the heart is involved, symptoms may include inflammation and thickening of the valves of the heart (valvar heart disease) potentially resulting in complication such as 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).

Additional organ systems may be involved including the gastrointestinal system, resulting in abdominal pain and cramping; the adrenal and pituitary glands resulting in hormone imbalances and low blood pressure; and the bone marrow resulting in low levels of red blood cells (anemia) and platelets (thrombocytopenia).

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Causes

Asherson’s syndrome is a rare autoimmune disorder. 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 autoimmune disorders.

Asherson’s syndrome is a variant of antiphospholipid syndrome, which is characterized by the presence of certain antibodies in the body and the development of blood clots. The antibodies that are present in both antiphospholipid syndrome and Asherson’s syndrome are known as antiphospholipid antibodies. There are several different types of antiphospholipid antibodies. 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 beta2-glycoprotein and prothrombin. The exact mechanism by which these antibodies eventually lead to the development of blood clots is not known.

Asherson’s syndrome may develop in individuals who already have primary or secondary antiphospholipid syndrome. It may also develop in individuals without a previous history of these disorders. The exact cause of Asherson’s is unknown. In some cases, researchers have identified a precipitating event or “trigger” that plays a role in the development of the multiple blood clots that characterize this disorder. The main trigger is infection. Additional triggers are trauma including trauma caused by invasive surgical procedures, withdrawal of anti-clotting medication, pregnancy, and certain underlying malignancies (cancers).

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Affected populations

Approximately 300 individuals have been identified with Asherson’s syndrome since the disorder was first defined in the medical literature in 1992. More women have been affected than men. The disorder can occur at any age, although most cases have been reported in young adults.

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Disorders with Similar Symptoms

Symptoms of the following disorders can be similar to those of Asherson’s syndrome. Comparisons may be useful for a differential diagnosis.

Thrombotic thrombocytopenia purpura (TTP) is a rare blood disorder characterized by the development of blood clots in small blood vessels (thrombotic microangiopathy). TTP appears to occur most often in females in the third or fourth decade of life. Findings may include low levels of platelets in the blood (thrombocytopenia), a diminished number of circulating red blood cells (microangiopathic hemolytic anemia), and/or neurological abnormalities. Thrombocytopenia is associated with a variety of symptoms including the development of purple bruises on the skin, hematuria, and/or small red or purple spots on the skin and/or mucous membranes (petechiae). Neurological abnormalities may include disorientation, headaches, visual abnormalities, seizures, paralysis (paresis), and/or, in severe cases, coma. In addition, affected individuals may also experience fever, fatigue, weakness, abdominal pain, and/or diarrhea. In some cases, individuals with TTP may experience acute renal failure, which may result in diminished excretion of urine; blood appearing in the urine (hematuria); high blood pressure (hypertension); an abnormal accumulation of fluid between layers of tissue under the skin (edema); and/or unusually low water content in the body (dehydration). In some cases, acute renal failure may lead to life-threatening complications. The exact cause of TTP is not known. (For more information on this disorder, choose “thrombotic thrombocytopenia purpura” as your search term in the Rare Disease Database.)

Hemolytic-Uremic syndrome (HUS) is a very rare disorder that primarily affects young children between the ages of one and 10 years, particularly those under the age of four years. In many cases, the onset of HUS is preceded by a flu-like illness (gastroenteritis) characterized by vomiting, abdominal pain, fever, and diarrhea, which, in some cases, may be bloody. Symptoms of HUS usually become apparent three to 10 days after the development of gastroenteritis and may include sudden paleness (pallor), irritability, weakness, lack of energy (lethargy), and/or excretion of abnormally diminished amounts of urine (oliguria). The disease typically progresses to include inability of the kidneys to process waste products from the blood and excrete them into the urine (acute renal failure), a decrease in circulating red blood cells (microangiopathic hemolytic anemia); a decrease in circulating blood platelets, which assist in blood clotting functions (thrombocytopenia); and the abnormal accumulation of platelets within certain blood vessels (microthrombi), reducing the blood flow to several organs (e.g., kidneys, pancreas, brain) potentially leading to multiple organ dysfunction or failure. In some cases, neurological problems may be present at the onset of HUS or may occur at any time during the disorder’s progression. Neurological symptoms may include dizziness, seizures (partial or generalized), disorientation or confusion, and/or loss of consciousness (coma). The onset of HUS is most frequently associated with infection by a particular strain (O157:H7) of Escherichia coli (E. coli) bacterium. (For more information on this disorder, choose “hemolytic uremic syndrome” as your search term in the Rare Disease Database.)

HELLP is a rare syndrome that affects some pregnant women. The acronym HELLP stands for Hemolysis, the premature destruction of red blood cells, Elevated Liver enzymes, and Low Platelet counts. Platelets are small blood cells that clump together to form a plug (clot) at the site of injury to a blood vessel. HELLP syndrome may occur as an isolated condition or in women who have preeclampsia. Affected women may experience nausea and vomiting, headaches, fatigue, upper abdominal pain and vision problems. The severity of HELLP syndrome varies; it can be a mild condition or can cause life-threatening complications. The exact cause of HELLP syndrome is unknown.

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Diagnosis

A diagnosis of Asherson's syndrome is made based upon a thorough clinical evaluation, identification of characteristic findings (e.g., multiple blood clots affecting at least three different organ systems that arise simultaneously within one week), and a variety of tests including simple blood tests that can detect antiphospholipid antibodies.

A specialized blood test called a coagulation test is used to measure blood clotting and can indicate the presence of lupus anticoagulant in the blood. An Enzyme-Linked ImmunoSorbent Assay (ELISA) test can detect the presence of anticardiolipin antibodies in the blood. Positive tests may often need to 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.

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Standard Therapies

Treatment

Because of the recent identification and limited number of cases of Asherson's syndrome, no standard therapy has been approved. Researchers who have studied the disease recommend a combination of therapeutic regimens including drugs that prevent clotting (anticoagulants), corticosteroids, specialized proteins known as immunoglobulins, and repeated plasma exchanges using a procedure called plasmapheresis.

Initial therapy for individuals is usually the anticoagulant, heparin, delivered intravenously. Corticosteroids may be given along with heparin. Steroids are given to minimize the effects of tissue loss (necrosis) that often accompanies Asherson's syndrome. Specialized proteins called immunoglobulins have also been used to treat affected individuals.

Repeated plasma exchanges using fresh frozen plasma may be given using a procedure known as plasmapheresis. Plasmapheresis is a method for removing unwanted substances (e.g., antiphospholipid antibodies) from the blood. Blood is removed from the patient and blood cells are separated from plasma. The patient's plasma is then replaced with other human plasma and the blood is transfused into the patient. This therapy is still under investigation to analyze side effects and effectiveness.

Intensive antibiotic therapy may be used to treat infection.

More research into the long-term effects of Asherson's syndrome is necessary, but researchers studying Asheron's have indicated that affected individuals who survive the initial onset of multiple blood clots have had an excellent prognosis so far.

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Clinical Trials and Studies

In 2000, the Catastrophic Antiphospholipid Syndrome (CAPS) Registry was created to document the clinical, laboratory and therapeutic information on affected individuals. The registry is overseen by the European Forum on Antiphospholipid Antibodies. For more information visit: www.med.ub.es/MIMMUN/FORUM/CAPS.HTM

The drug Rituximab has been used successfully to treat individuals with Asherson’s syndrome who experience severe thrombocytopenia. Additional drugs have been used to treat Asherson’s syndrome including drugs that suppress the immune system (e.g., cyclophosphamide) or drugs that break down blood clots or prevent platelets or clots from forming (fibrinolytic drug) such as prostacyclin. More research is necessary to determine the long-term and safety and effectiveness of these potential therapeutic agents for Asherson’s syndrome.

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:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: [emailprotected]

For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

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Resources

Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.

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References

TEXTBOOKS

Hogan WJ, Nichols WL. Antiphospholipid Syndrome. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:2.

Lichtman MA, Beutler E, Kipps TJ, Selisohn U, et al. Eds. Williams Hematology. 7th ed. McGraw-Hill Companies. New York, NY; 2006:2009-29.

JOURNAL ARTICLES

Baryraktar UD, Erkan D, Bucciarelli S, et al., The clinical spectrum of catastrophic antiphospholipid syndrome in the absence and presence of lupus. J Rheumatol. 2007;34:346-52.

Asherson RA. The catastrophic antiphospholipid (Asherson’s) syndrome. Autoimmun Rev. 2006;6:64-7.

Merrill JT, Asherson RA. Catastrophic antiphospholipid syndrome. Nat Clin Pract Rheumatol. 2006;2:81-9.

Cervera R, Espinosa G, Bucciarelli S, Gomez-Puerta AJ, Font J. Lessons from the catastrophic antiphospholipid syndrome (CAPS) registry. Autoimmun Rev. 2006;6:81-4.

Miesback W, Asherson RA, Cervera R, et al., The catastrophic antiphospholipid (Asherson’s) syndrome and malignancies. Autoimmun Rev. 2006;6:94-7.

Asherson RA. The catastrophic antiphospholipid (Asherson’s) syndrome. Autoimmun Rev. 2006;6:61-7.

Cervera R, Font J, Gomez-Puerta JA, et al., Validation of the preliminary criteria for the classification of catastrophic antiphospholipid syndrome. Ann Rheum Dis. 2005;64:1205-9.

Borba EF, Bonfa E, Asherson RA. Catastrophic antiphospholipid syndrome (Asherson’s syndrome) revealed. Rev Bras Reumatol. 2005;45:374-81.

Misita CP, Moll S. Antiphospholipid antibodies. Circulation. 2005;112:e39-44.

Erkan D, Asherson RA, Espinosa G, et al., Long term outcome of catastrophic antiphospholipid syndrome survivors. Ann Rheum Dis. 2003;62:530-3.

FROM THE INTERNET

Tektonidou M. Antiphospholipid Syndrome. Orphanet encyclopedia, September 2003. Available at: https://www.orpha.net/data/patho/Pro/en/Antiphospholipid-FRenPro5517.pdf Accessed on: March 9, 2007.

Carsons S. Antiphospholipid Syndrome. Emedicine Journal, December 5, 2004. Available at: https://www.emedicine.com/med/topic2923.htm Accessed on: March 9, 2007.

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