Related Terms

• Antibodies, APLA, APLS, APS, autoimmune disorder, blood clotting, catastrophic antiphospholipid syndrome, heart attack, Hughes syndrome, miscarriage, phospholipid antibody syndrome, sticky blood, stroke.

Background

• Antiphospholipid syndrome (APS), also called Hughes syndrome or phospholipid antibody syndrome, is a condition in which patients experience frequent incidences of blood clotting.

• A blood clot is a clump that results from the hardening of blood. Blood clots may cut off the circulation of blood to other parts of the body. About one to five percent of people are thought to be affected with APS. Women are affected more frequently than men. APS most frequently affects middle-aged adults, but it may also occur in infants and the elderly.

• The blood clots in patients with APS can be life threatening, as they may lead to a heart attack or stroke. Blood clots may appear in arteries or veins throughout the body in any organ system, and they appear frequently in blood vessels of the legs.

• APS is an autoimmune condition. Normally, the immune system attacks foreign invaders, such as bacteria. An autoimmune condition occurs when the immune system malfunctions and begins to attack normal components of the body in addition to foreign invaders. In the case of APS, the immune system attacks proteins normally found in the blood, causing clots to form. These include a protein called cardiolipin, a protein called β2 glycoprotein I, and a protein called annexin V.

• Currently, there is no known cure for APS. However, treatments exist to help manage the symptoms. If treated properly, most patients are able to live normal lives.

Risk Factors

• Antiphospholipid syndrome (APS) is an autoimmune condition (the immune system malfunctions and attacks normal components of the body). Individuals who have other autoimmune conditions (such as systemic lupus erythematosus, a condition leading to inflammation of body tissues) may be at greater risk of developing APS.

• Some evidence suggests that APS may be due to inheritance of a defective gene because it has been reported to occur within multiple members of a family. However, a clear inheritance pattern has not yet been identified. Also, a gene or mutation that causes APS has not been identified.

• It is possible to have antiphospholipid antibodies without having APA; approximately two percent of the population who does not have APS has antiphospholipid antibodies in their blood. In these people, the antibodies appear to be harmless.

Causes

• In antiphospholipid syndrome (APS), the immune system attacks proteins normally found in the blood or on the membrane of cells, causing clots to form. The exact cause of APS is not known. In patients with APS, some antibodies produced by the immune system don't function correctly. These malfunctioning antibodies are able to bind to specific proteins in patients with APS, including a protein called cardiolipin, a protein called β2 glycoprotein I, and a protein called annexin V. Annexin V has strong clot blocking activity, so the binding of antibodies to Annexin V may cause increased clotting in patients. Cardiolipin normally functions in the mitochondrion (a compartment of the cell that generates energy). The normal function of β2 glycoprotein I is unclear.

• The term antiphospholipid syndrome has been used because the malfunctioning antibodies were originally thought to bind to phospholipids, which are components of the cell membrane. Phospholipids have one region that has an affinity to water and one region that repulses water. They serve as a major structural component of the cell membrane. It is now known that the malfunctioning antibodies in APS do not attack phospholipids, but rather they attack proteins in the blood of APS patients. However, some of these proteins are able to bind to phospholipids, which likely led to some confusion during early research of the disease.

Signs and Symptoms

• Blood clotting: Patients with antiphospholipid syndrome (APS) have a high risk of developing blood clots. Patients with APS may develop blood clots in their veins or arteries. Depending on where in the body they form, blood clots may lead to muscle pain or spasm, numbness, shortness of breath, rapid breathing, sudden cough, heart attack, or stroke. They may also cause decreased blood flow to a certain region of the body.

• Cardiovascular problems: Patients with APS may also have decreased numbers of platelets (these are small cells that function in blood clotting) and they may experience problems with their heart valves (specifically, growths may break off from the heart valve and block a blood vessel).

• Neurological problems: Some patients with APS experience neurological symptoms, including loss of concentration, headaches, dizziness, or episodes of vision or memory loss. Also, some patients experience a rare form of inflammation of the nervous tissue of the brain or spinal cord called transverse myelitis.

• Rash: A net-like reddish blue rash called livedo reticularis may develop on the skin of some patients with APS.

Diagnosis

• A combination of symptoms and diagnostic tests is used to diagnose antiphospholipid syndrome (APS). Misdiagnosis frequently occurs in patients with APS because doctors do not always carry out diagnostic tests (which can more accurately diagnose the condition) after symptoms appear. This may be because some primary care doctors are uninformed about APS. APS may also be misdiagnosed because some individuals have antiphospholipid lipid antibodies in the blood, but don't develop the disease.

• Symptoms: Observation of symptoms associated with APS is used to help in the diagnosis of this disorder. Doctors may check for a history of blood clots, especially severe cases of clots that may have resulted in heart attack or stroke, as well as for the presence of a net-like reddish blue rash called livedo reticularis. Doctors may also check for the presence of neurological symptoms (such as headaches, dizziness, or memory loss) and they may ask women if they have ever experienced any miscarriages or other complications during pregnancy.

• Diagnostic tests: If APS is suspected, diagnostic tests may be performed to more accurately diagnose the condition. APS is known to be caused by the formation of abnormal antibodies (antibodies are a component in the immune system that normally function to fight foreign invaders in the body). Blood tests exist that can be used to check for the presence of some of these abnormal antibodies and help provide a diagnosis. One commonly used diagnostic test checks for the presence of anticardiolipin antibodies. Another test checks for the presence of antibodies to β2 glycoprotein I. Other blood tests exist that can be used to check for abnormal blood clotting in patients (such as the lupus anticoagulant test) or to check for abnormally low numbers of platelets.

Complications

• The blood clots that form in patients with antiphospholipid syndrome (APS) may lead to a variety of life-threatening complications. These include heart attack, stroke (a condition in which the blood supply to the brain is blocked), or pulmonary embolism (a condition in which the blood supply to the lungs is blocked). These conditions may result in death in patients with APS.

• Miscarriage: In pregnant women, APS may lead to an increased risk of having a miscarriage. This is because blood clots may form in the placenta, which can prevent nutrients from reaching the fetus. A miscarriage in a patient with APS is most common in the late first trimester or early second trimester. APS may lead to other problems in pregnant women, including premature delivery or delayed fetal growth.

• Catastrophic antiphospholipid syndrome: In rare cases, and for unknown reasons, patients with APS may experience sudden and severe formation of clots throughout the body, which affects many organ systems and usually leads to death. This condition progresses rapidly and is called catastrophic antiphospholipid syndrome.

Treatment

• There is no known cure for antiphospholipid syndrome (APS). However, treatments exist that may help patients manage some of the symptoms. If treated properly, most patients remain healthy and can live normal lives.

• Anticoagulants: The main treatment for APS is anticoagulant therapy. An anticoagulant is a medication that slows down the body's ability to make blood clots. Warfarin, aspirin, and heparin are commonly used anticoagulants in the treatment of APS. It is often recommended that patients with APS take anticoagulants indefinitely, as continued use of anticoagulants may reduce or prevent clots from forming in the future. Patients should consult with a qualified healthcare professional to determine the best treatment option.

• A side effect for patients taking anticoagulants is that injuries such as cuts may bleed longer and could be more serious, because the blood clots more slowly.

• Lifestyle: It is recommended that patients with APS make healthy lifestyle choices, including exercising regularly, maintaining a healthy weight, and not smoking. Making healthy lifestyle choices may reduce a patient's risk of developing clots.

Integrative Therapies

• Note: There is evidence that several integrative therapies, such as policosanol, aortic acid, garlic, ginger, Pycnogenol®, rutin, seaweed, kelp, and bladderwrack, may reduce the formation of blood clots or the aggregation of platelets. While the use of these therapies to treat antiphospholipid syndrome has not been well studied, these therapies may potentially be effective in treating the disease, based on the symptoms that the patients exhibit.

• The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider, and should not be used in replacement of other proven therapies or preventive measures.

• Strong scientific evidence:

• Policosanol: Policosanol is a natural product made from the waxy coating of sugar cane that helps lower cholesterol. Various studies have investigated the effect of policosanol on platelet aggregation. In general, studies suggest that policosanol inhibits platelet aggregation caused by collagen and arachidonic acid.

• Avoid if allergic or hypersensitive to policosanol. Use cautiously with nitrates, aspirin, or drugs that lower cholesterol or blood pressure. Avoid if pregnant or breastfeeding.

• Unclear or conflicting scientific evidence:

• Aortic acid: Aortic extract is usually made from the hearts of animals, usually sheep, cows, or pigs. There are many substances in this extract, including aortic acid, which is a broad term encompassing several constituents. Mesoglycan is the most studied of these constituents. Further research is needed to determine whether or not aortic acid may help treat patients with deep vein thrombosis (DVT).

• Reports of allergic reactions with use of aortic acid are currently unavailable. Due to the heparin sulfate content of mesoglycan, patients with an allergy to heparin or heparinoid derivatives should use aortic acid cautiously. Use cautiously with coagulation disorders or if taking anticoagulation therapy. Use cautiously with high blood pressure or if taking drugs that lower blood pressure. Avoid if pregnant or breastfeeding.

• Garlic: The garlic bulb is made of many garlic cloves that are wrapped in a paper-thin, white skin. Garlic, which is often used as a spice in food, has also been used to treat many medical conditions. Garlic has been studied in humans as a possible anticoagulant therapy. Because garlic has been associated with several cases of bleeding, therapy should be used cautiously, especially in patients who are taking other medications, herbs, or supplements that may increase the risk of bleeding.

• Avoid if allergic or hypersensitive to garlic or other members of the Lilaceae(lily) family (e.g. hyacinth, tulip, onion, leek, or chive). Avoid with a history of bleeding problems, asthma, diabetes, low blood pressure, or thyroid disorders. Stop using supplemental garlic two weeks before and immediately after dental/surgical/diagnostic procedures to avoid bleeding problems. Avoid supplemental doses if pregnant or breastfeeding.

• Ginger: The underground stems (rhizomes) and above ground stems of ginger have been used in Chinese, Japanese, and Indian medicine for hundreds of years. One study suggests that ginger may increase the effects of the anti-platelet medication nifedipine in patients who have high blood pressure. Further research is necessary to determine if ginger might be used as an anticoagulant therapy.

• Avoid if allergic to ginger or other members of the Zingiberaceaefamily, including red ginger, Alpinia purpurata, shell ginger, Alpinia zeru, green cardamom, or Balsam of Peru. Use cautiously if driving or operating machinery because ginger may cause drowsiness. Stop two weeks before and immediately after surgery/dental/diagnostic procedures due to risk of bleeding. Avoid with a history of irregular heartbeat (arrhythmia). Use cautiously with a history of ulcers, acid reflux, heart conditions, inflammatory bowel disease, blocked intestines, or bleeding disorders. Use cautiously if pregnant or breastfeeding.

• Pycnogenol: Pycnogenol® is the patented trade name for a water extract of the bark of the French maritime pine tree (Pinus pinaster ssp. atlantica), which is grown in coastal southwestern France. Pycnogenol® contains oligomeric proanthocyanidins (OPCs), as well as several other bioflavonoids: catechin, epicatechin, phenolic fruit acids (such as ferulic acid and caffeic acid), and taxifolin. According to the results of one human study, Pycnogenol® may reduce platelet aggregation in smokers. However, further research is needed before a firm conclusion can be made.

• Pycnogenol® treatment may effectively decrease the number of thrombotic events (deep vein thrombosis and superficial vein thrombosis) in moderate- to high-risk subjects, during long-haul flights. Edema (swelling) may also be reduced. Further research is needed to confirm these results.

• Avoid if allergic or hypersensitive to Pycnogenol®, its components, or members of the Pinaceae family. Use cautiously with diabetes, hypoglycemia, bleeding disorders. Use cautiously if taking hypolipidemic agents (drugs that lower cholesterol), medications that may increase the risk of bleeding, hypertensive medications, or immune stimulating or inhibiting drugs. Avoid if pregnant or breastfeeding.

• Rutin: Rutin is a yellow crystalline flavonol glycoside that occurs in various plants, especially the buckwheat plant, black tea, apple peels, onions, and citrus. Superficial vein thrombosis (SVT) is a common complication of varicose veins. One clinical trial suggests that a rutin-containing drug called Venoruton®, in combination with elastic compression or thrombectomy, offers benefit as compared to these treatments alone. Additional study is needed in this area.

• Avoid if allergic or hypersensitive to O-(beta-hydroxyethyl)-rutosides or plants that rutin is commonly found in, such as rue, tobacco, or buckwheat. Use cautiously in elderly patients. Use cautiously with skin conditions. Use cautiously if taking medications for edema, diuretics, or anticoagulation medications (e.g. heparin or warfarin). Use cautiously if pregnant or breastfeeding.

• Seaweed, kelp, bladderwrack: Bladderwrack (Fucus vesiculosus) is a brown seaweed found along the northern coasts of the Atlantic and Pacific oceans and North and Baltic seas. Another seaweed that grows alongside bladderwrack is Ascophyllum nodosum, andit is often combined with bladderwrack in kelp preparations. Laboratory study has found anticoagulant properties in fucans or fucoidans, which are components of brown algae such as bladderwrack. However, high quality human studies are currently unavailable to support this use.

• Avoid if allergic or hypersensitive to Fucus vesiculosus or iodine. Avoid with a history of thyroid disease, bleeding, acne, kidney disease, blood clots, nerve disorders, high blood pressure, stroke, or diabetes. Avoid if pregnant or breastfeeding.

Prevention

• There are currently no known ways to prevent antiphospholipid syndrome (APS). Some treatments, such as anticoagulant therapy and lifestyle modifications, are available for patients.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

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3. Hughes Syndrome Foundation. www.hughes-syndrome.org Accessed January 23, 2007

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5. National Institute of Neurological Disorders and Stroke. www.ninds.nih.gov Accessed January 23, 2007

6. Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com.

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