Patient information: The antiphospholipid syndrome

ANTIPHOSPHOLIPID SYNDROME OVERVIEW

Blood clotting is a normal process that helps to prevent excessive blood loss. Blood clotting involves a number of different steps and many different substances.

Phospholipids are a type of fat that are present on blood cells and the lining of blood vessels. In some people, the immune system develops antibodies to these phospholipids. Antibodies to the phospholipids increase the risk of developing blood clots in the veins or arteries and 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). Antiphospholipid syndrome 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 women and in patients with other autoimmune or rheumatic diseases, particularly systemic lupus erythematosus (SLE). APS is referred to as "primary" when it occurs alone, and as "secondary" when it occurs in association with another disorder. (See "Patient information: Systemic lupus erythematosus (SLE)".)

ANTIPHOSPHOLIPID SYNDROME SYMPTOMS

The symptoms of APS are related to abnormal blood clotting.

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 or 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 information: Deep vein thrombosis (DVT)".)

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.

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, 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.

Miscarriages — In women with APS, antiphospholipid antibodies can increase the risk of miscarriage or stillbirth. (See 'Antiphospholipid syndrome and pregnancy' below.)

ANTIPHOSPHOLIPID SYNDROME DIAGNOSIS

A diagnosis of 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, 3 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, 12 weeks apart. Antiphospholipid antibodies 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 prevent the formation of additional blood clots. Anticoagulants are commonly, but incorrectly, referred to as blood thinners.

Patients with APS are often treated with an injectable anticoagulant called heparin or low molecular weight heparin. In some cases, the heparin is given into a vein while the patient is in the hospital. In other cases, heparin is injected into the skin.

There are several types of low molecular weight heparin, including enoxaparin (Lovenox®), dalteparin (Fragmin®), or tinzaparin (Inohep®). These can be injected into 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 information: Warfarin (Coumadin®)".)

Monitoring of warfarin — Careful monitoring and periodic adjustments in the warfarin dose are typically needed to maintain a level that prevents clots but 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 INR (or International Normalized Ratio). 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 blood clots. Aspirin alone may be recommended for patients who have experienced a single, less severe, blood clot.

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 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 APS have an increased risk of developing a thrombosis (blood clot in a vein or artery) and having a miscarriage compared to pregnant women without APS. They may also be at risk for other pregnancy-related complications, including preeclampsia and decreased blood flow to the fetus.

Several treatments are available to reduce these risks. Treatment depends upon the woman's previous history of blood clots, miscarriage, stillbirth, preeclampsia, and 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, and is usually stopped sometime after 36 weeks of gestation. Aspirin can be restarted after delivery, and is usually taken for at least six to eight weeks postpartum.

Heparin — Heparin must be given as an injection, either into the skin or 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 to 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. If warfarin is used, it must be stopped before 6 weeks of pregnancy. It may be restarted after 14 weeks of pregnancy, but must be discontinued by 36 weeks of pregnancy. Another anticoagulant (eg, heparin) is usually recommended when warfarin is not used.

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 information: Birth control; which method is right for me?".)

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Systemic lupus erythematosus (SLE)
Patient information: Deep vein thrombosis (DVT)
Patient information: Warfarin (Coumadin®)
Patient information: Birth control; which method is right for me?

Professional Level Information:
Antiphospholipid syndrome and the kidney
Clinical manifestations of the antiphospholipid syndrome
Diagnosis of the antiphospholipid syndrome
Management of pregnant women with antiphospholipid antibodies or the antiphospholipid syndrome
Obstetrical manifestations of the antiphospholipid syndrome
Pathogenesis of the antiphospholipid syndrome
Treatment of the antiphospholipid syndrome

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• National Institute of Neurological Disorders and Stroke

      (www.ninds.nih.gov/disorders/antiphosphlipid/antiphospholipid.htm)

• American Academy of Family Physicians

      (www.familydoctor.org)

• American College of Rheumatology

      (www.rheumatology.org)

      phone: 404-633-3777

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