Patient education: The antiphospholipid syndrome (Beyond the Basics)
- Doruk Erkan, MD, MPH
Doruk Erkan, MD, MPH
- Associate Attending Rheumatologist, Hospital for Special Surgery
- Associate Professor of Medicine, Weill Cornell Medicine
ANTIPHOSPHOLIPID SYNDROME OVERVIEW
Phospholipids are present in the membranes that form the surface of cells, including blood cells and endothelial cells that line blood vessels. In some people, the immune system develops antibodies to proteins that are attached to phospholipids. The presence of these antiphospholipid antibodies may increase the risk of developing blood clots in the veins or arteries and may also cause an increased risk of miscarriage or stillbirth among pregnant women. However, some people have these antibodies and do not develop clots or have miscarriages.
People who have these antibodies and develop blood clots or pregnancy-related complications are said to have a syndrome called the antiphospholipid syndrome (APS). APS is an autoimmune disorder, meaning that it occurs when the body's immune system mistakenly attacks healthy tissues and organs.
APS is more common in patients with other autoimmune or rheumatic diseases, particularly systemic lupus erythematosus (SLE). APS is referred to as “primary” when it occurs alone. (See "Patient education: Systemic lupus erythematosus (SLE) (Beyond the Basics)".)
ANTIPHOSPHOLIPID SYNDROME SYMPTOMS
The symptoms of antiphospholipid syndrome (APS) are related primarily to abnormal blood clotting, miscarriage, or stillbirth.
Thrombosis (blood clot) — The presence of antiphospholipid antibodies can increase the risk of developing a thrombosis (blood clot) in a vein or artery. Without treatment, patients often experience repeated clots. Blood flow to and function of important organs can be affected, depending upon where the clot is located.
Many organs are susceptible to injury from blood clots. A clot that forms in or blocks an artery can impair blood flow to the brain, causing problems ranging from brief, reversible neurologic symptoms to a stroke that causes permanent brain damage. Impaired blood flow to the kidney can cause problems ranging from mild kidney dysfunction to kidney failure.
Clots in large veins can lead to pain and swelling of the affected limb. This is referred to as a deep venous thrombosis (DVT). Legs are most often affected, but the arms can occasionally be involved. In addition to the pain and swelling that such blood clots cause, there is also a risk that a large clot will break free and travel through the heart to the blood vessels of the lungs, where it can block blood flow. A clot that travels is called an embolus; an embolus in the lung is called a pulmonary embolism. (See "Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)".)
If a large vessel in the lung is blocked due to a pulmonary embolus, a person may feel chest pain, difficulty breathing, and sometimes coughs up of blood. Very large clots can lead to fainting or even death.
Miscarriages — In women with APS, antiphospholipid antibodies can increase the risk of miscarriage or stillbirth. (See 'Antiphospholipid syndrome and pregnancy' below.)
Thrombocytopenia — In some patients, APS leads to a decrease in the number of cells known as platelets. This condition is known as thrombocytopenia.
Platelets are essential to the normal blood clotting process. When the number of platelets is significantly lowered (to less than 30,000), there is a risk of bleeding, particularly from the nose and gums, into the skin (called petechiae), from the digestive tract, and from the uterus in women. In patients with APS, however, the reduced number of platelets may be associated with an increased risk of blood clots rather than bleeding problems.
Some of the other potential clinical problems that can occur in APS patients include anemia, heart valve disease, skin rashes and/or ulcers, and memory problems.
ANTIPHOSPHOLIPID SYNDROME DIAGNOSIS
A diagnosis of antiphospholipid syndrome (APS) is based upon a patient's history and laboratory findings. The diagnosis requires the following:
●An episode of blood clots, one or more miscarriages after the 10th week of pregnancy, three or more miscarriages prior to the 10th week of pregnancy, or one or more premature births prior to the 34th week of pregnancy due to eclampsia.
●Antiphospholipid antibodies detected with blood testing on at least two different occasions at least 12 weeks apart. Antiphospholipid antibody tests include the lupus anticoagulant, anti-cardiolipin antibodies, and anti-beta-2-glycoprotein I antibodies.
TREATMENT AND PREVENTION OF BLOOD CLOTS
Anticoagulants — Anticoagulants are medications that prevent an existing blood clot from enlarging and that prevent the formation of additional blood clots. Anticoagulants are commonly, but incorrectly, referred to as blood thinners.
Patients with antiphospholipid syndrome (APS) are often treated with an injectable anticoagulant called heparin or low molecular weight heparin (LMWH). In some cases, the heparin is given into a vein while the patient is in the hospital. In other cases, heparin is injected under the skin.
There are several types of LMWH, including enoxaparin (Lovenox), dalteparin (Fragmin), or tinzaparin (Innohep). These can be injected beneath the skin by the patient, a family member, or a home health nurse. This is usually continued for several days, along with another medication called warfarin (Coumadin). Warfarin is an anticoagulant medication that is taken by mouth, as a pill. Heparin can be stopped once warfarin levels are stable. (See "Patient education: Warfarin (Coumadin) (Beyond the Basics)".)
Monitoring of warfarin — Careful monitoring and periodic adjustments in the warfarin dose are typically needed to maintain a level that prevents clots but that does not cause significant bleeding. The blood test used to measure the effects of warfarin is called the prothrombin time (called pro time, or PT). The PT is a laboratory test that measures the time it takes for the clotting mechanism to progress. It is particularly sensitive to the clotting factors affected by warfarin. The PT is used to compute a value known as the International Normalized Ratio (INR). The INR is a way of expressing the PT in a standardized way; this ensures that results obtained by different laboratories can be reliably compared.
The longer it takes the blood to clot, the higher the PT and INR. The target INR range depends upon the clinical situation. In most cases, the target range is 2 to 3. If the INR is below the target range (ie, under-anticoagulated), there is a risk of clotting. If, on the other hand, the INR is above the target range (ie, over-anticoagulated), there is an increased risk of bleeding.
Antiplatelet treatments — Aspirin is another medication sometimes recommended for people with APS. Aspirin inhibits the clumping of platelets; platelets are tiny cell fragments in the blood that have a role in blood clotting. Under normal circumstances, platelets clump together and help form blood clots to stop bleeding when needed.
Aspirin is sometimes used in addition to warfarin. It is not usually used as a replacement for warfarin, especially in patients with a history of serious and recurrent blood clots.
Treatment before and during surgery — Anticoagulant and antiplatelet treatments may need to be adjusted before, during, and after surgery or other procedures that have a risk of bleeding. The goal of treatment adjustments is to minimize the risk of new blood clots as well as the risk of excessive bleeding. This usually involves stopping warfarin several days before surgery.
The patient may be given heparin before and after surgery, depending upon several factors (the patient's previous history of thrombosis, type of surgery, etc). Warfarin can usually be restarted within 12 hours after surgery. Patients should speak with the provider who prescribes their warfarin to determine the best treatment regimen before and after surgery.
TREATMENT OF LOW PLATELETS
Patients with mild thrombocytopenia (low platelet count) due to antiphospholipid syndrome (APS) usually require no treatment. In more severe cases, medications (including steroids or immune globulins) are used to help increase the platelet count.
ANTIPHOSPHOLIPID SYNDROME AND PREGNANCY
Pregnant women with antiphospholipid syndrome (APS) have an increased risk of developing a thrombosis (blood clot in a vein or artery) and of having a miscarriage compared with pregnant women without APS. They may also be at risk for other pregnancy-related complications, including preeclampsia and decreased blood flow to the fetus resulting in intrauterine growth restriction.
Several treatments are available to reduce these risks. Treatment depends upon the woman's previous history of blood clots, miscarriage, stillbirth, and preeclampsia and upon her current antibody levels. For women who have antiphospholipid antibodies but no history of blood clots or miscarriage, treatment may or may not be recommended.
The following is a general description of available treatments.
Aspirin — Low-dose aspirin may be used for pregnant women with APS in combination with other treatments, including heparin injections. Low-dose aspirin can be started before the woman attempts to become pregnant.
Heparin — Heparin must be given as an injection, either under the skin or into a vein. Most pregnant women who use heparin are taught to give their own injections into the skin.
There are two types of heparin: unfractionated and low molecular weight heparin (LMWH).
●Unfractionated heparin must be injected twice per day and has a risk of causing excessive bleeding, a low platelet count, and osteoporosis.
●LMWH is usually injected once per day and has a lower risk of excessive bleeding, low platelet count, and bone thinning (osteoporosis) compared with unfractionated heparin.
Heparin is usually started once pregnancy is confirmed and is usually stopped temporarily for planned procedures (eg, amniocentesis, cesarean section) and when labor begins. Either heparin or warfarin is recommended for six to eight weeks after delivery.
Warfarin — Warfarin is not usually recommended for pregnant women with APS because of the potential risks to the developing fetus. Warfarin must be stopped before six weeks of pregnancy.
Warfarin can be restarted after delivery and is often the preferred treatment for women with APS during the postpartum stage (the six to eight weeks following delivery). Warfarin is safe to take while breastfeeding.
Preventing pregnancy — Women with APS should not use birth control methods that contain estrogen because estrogen can increase the risk of developing a blood clot. A number of other methods of birth control are available, including progestin-only pills, an intrauterine device, condoms, a diaphragm, an injection (eg, Depo Provera), or a surgical procedure. These options are discussed separately. (See "Patient education: Birth control; which method is right for me? (Beyond the Basics)".)
WHERE TO GET MORE INFORMATION
Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
This topic currently has no corresponding Basic content.
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient education: Systemic lupus erythematosus (SLE) (Beyond the Basics)
Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)
Patient education: Warfarin (Coumadin) (Beyond the Basics)
Patient education: Birth control; which method is right for me? (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Antiphospholipid syndrome and the kidney
Clinical manifestations of antiphospholipid syndrome
Diagnosis of antiphospholipid syndrome
Pregnancy in women with antiphospholipid syndrome
Pathogenesis of antiphospholipid syndrome
Treatment of antiphospholipid syndrome
The following organizations also provide reliable health information.
●National Library of Medicine
●National Institute of Neurological Disorders and Stroke
●American Academy of Family Physicians
●American College of Rheumatology
●APS ACTION (APS Alliance for Clinical Trials & International Networking)
- Cervera R, Piette JC, Font J, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46:1019.
- Crowther MA, Ginsberg JS, Julian J, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003; 349:1133.
- Farquharson RG, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol 2002; 100:408.
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.