Pregnancy complications

• Pregnancy complications may need special medical care.
• Common problems include anemia, diabetes and bleeding.
• Ask your provider about the signs of serious complications.

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The thrombophilias are a group of disorders that promote blood clotting. Individuals with a thrombophilia tend to form blood clots too easily, because their bodies make:

• Too much of certain proteins, called blood clotting factors or
• Too little of anti-clotting proteins that limit clot formation

A thrombophilia can be inherited or acquired later in life. About 15 percent of people in the United States have an inherited thrombophilia (1, 2). Acquired thrombophilias are less common. Thrombophilias may pose special risks in pregnancy.

What are the symptoms of a thrombophilia?
Most people with a thrombophilia have no symptoms. However, some develop a thrombosis, a blood clot where it does not belong. Often, blood clots form in veins in the lower leg, causing swelling, redness and discomfort. This condition, called deep vein thrombosis, is often diagnosed with ultrasound or other imaging tests. Clots are generally treated with anticoagulant (blood-thinning) drugs.

Clots can become life-threatening if they break off and travel through the bloodstream to vital organs. This is called venous thromboembolism (VTE). When the VTE blocks blood vessels in the lungs, it is called a pulmonary embolus. It can cause serious breathing difficulties and sometimes death. VTEs that block blood vessels in the brain or heart can cause stroke or heart attack.

Clots are more likely to develop when a person with a thrombophilia has other risk factors, including:

• Having a family history of VTE in a parent, sibling or child
• Being pregnant or in the postpartum period (up to 6 weeks after delivery)
• Requiring immobilization (due to a bone fracture, for example) or surgery

What are the most common types of thrombophilias?
The inherited thrombophilias include:

• Factor V Leiden and prothrombin mutations: These are the most common inherited thrombophilias. They occur in 2 to 7 percent and 2 percent, respectively, of Caucasians, and are less common in African-Americans and Asians (2).
• Antithrombin, protein C and protein S deficiencies. Each affects less than 1 percent of people in the United States (2).

All of these are inherited in an autosomal dominant pattern, meaning that an affected person needs to inherit the gene from only one parent. Each child of an affected parent has a 50 percent chance of inheriting the thrombophilia.

The most common acquired thrombophilia is antiphospholipid syndrome (APS). APS occurs in up to 5 percent of pregnant women (3). In APS, the body makes antibodies that attack certain fats (phospholipids) that line the blood vessels, sometimes leading to blood clots. APS is an autoimmune disorder, like arthritis and systemic lupus erythematosus (SLE). Up to 40 percent of women with SLE have antiphospholipid antibodies in their blood, which may contribute to their increased risk of pregnancy complications (3).

What are the risks of a thrombophilia during pregnancy?
Most women with a tendency to develop clotting have healthy pregnancies. However, these pregnant women may be more likely than other pregnant women to develop deep vein clots and certain other pregnancy complications.

Even pregnant women without a clotting problem may be more likely than non-pregnant women to develop deep vein clots and emboli. This is due to normal pregnancy-related changes in blood clotting that limit blood loss during labor and delivery. However, studies suggest that at least 50 percent of pregnant women who develop a pulmonary embolus or other VTE have an underlying thrombophilia (1, 2). Pulmonary embolus is the leading cause of maternal death in the United States (2).

The thrombophilias also may contribute to pregnancy complications including (1):

• Repeated miscarriage, usually occurring after the tenth week of pregnancy
• Stillbirth in the second or third trimesters
• Placental abruption, a condition in which the placenta peels away from the uterine wall, partially or completely, before delivery. This can cause heavy bleeding that is dangerous for mother and baby.

APS contributes to 10 to 20 percent of repeated pregnancy losses (3, 4). APS also is associated with other pregnancy complications (4, 5):

• Preeclampsia. This pregnancy-associated form of high blood pressure can pose a number of risks for mother and baby.
• Poor fetal growth
• Premature delivery (before 37 completed weeks of pregnancy)

Health care providers believe that these problems may be caused by blood clots in placental vessels that reduce blood flow to the fetus. It is not yet known whether the inherited thrombophilias contribute to these pregnancy complications. To date, the risk, if any, appears low (1, 6).

How are the thrombophilias diagnosed?
Providers do blood tests to find out whether or not a person has a thrombophilia.

Which pregnant women should be tested for thrombophilias?
All pregnant women who have had a blood clot should be offered testing (1, 5). Health care providers also may recommend testing if a woman has:

• A family history of VTE before age 50
• A history of pregnancy complications, including two or more miscarriages after 10 weeks gestation, stillbirth, early or severe preeclampsia or severe unexplained fetal growth problems (1, 5)

How is a thrombophilia treated during pregnancy?
Treatment depends on the specific type of thrombophilia and whether or not a woman has had a blood clot in the past. Some women with a thrombophilia may not need treatment.

Women with a thrombophilia who have a history of blood clots are usually treated with an anticoagulant during pregnancy and the postpartum period. Women with certain severe, inherited thrombophilias (such as antithrombin deficiency) also are usually treated, even if they have not experienced blot clots (7). During pregnancy, these women are generally treated with an anticoagulant called heparin (given by injection one or more times daily) or a newer version of the drug called low-molecular weight heparin. These drugs do not cross the placenta and are safe for the baby. After delivery, some women with a thrombophilia may be treated for about 6 weeks with an oral anticoagulant called warfarin, in addition to, or instead of, heparin. Warfarin is safe to take during breastfeeding, but it is not recommended during pregnancy because it crosses the placenta and can cause birth defects.

Women with APS who have a history of blood clots and/or repeated pregnancy loss are usually treated with anticoagulants during pregnancy and the postpartum period. Low doses of aspirin may be recommended along with heparin for some women with APS. Studies suggest that the combination is more effective than either medication alone in preventing pregnancy loss (5, 7).

Not all women with a thrombophilia need treatment during pregnancy. A woman and her health care provider should discuss her individual risks of blood clots and pregnancy complications and the severity of her thrombophilia before deciding whether or not she needs treatment. Heparin treatment does pose some risk of side effects, including bone loss and potentially dangerous blood changes. The risks appear lower with low-molecular weight heparin.

Treatment may not be recommended for pregnant women with one of the less severe thrombophilias (such as factor V Leiden or prothrombin mutations) who have no personal or family history of blood clots (1, 7). The risk of VTE is less than 0.2 percent (1 in 500) in pregnant women with factor V Leiden with no personal or strong family history of VTE (1). In some cases, treatment may be recommended after a cesarean delivery.

Does the March of Dimes support research related to the thrombophilias?
Yes. March of Dimes grantees are studying the underlying genetic basis of various inherited blood diseases, some of which affect blood clotting. What they learn may lead to improved treatments for inherited blood diseases, possibly including the thrombophilias.

References

1. Lockwood, C.J. and Bauer, K.A. Inherited Thrombophilias in Pregnancy. UpToDate, January 30, 2009.
2. Marik. P.E. and Plante, L.A. Venous Thromboembolic Disease and Pregnancy. New England Journal of Medicine, volume 359, number 19, November 6, 2008, pages 2025-2033.
3. National Human Genome Research Institute. Learning About Antiphospholipid Syndrome (APS). Updated February 25, 2009.
4. Schur, P. The Antiphospholipid Syndrome. UptoDate, January 18, 2009.
5. American College of Obstetricians and Gynecologists (ACOG). Antiphospholipid Syndrome. ACOG Practice Bulletin, number 68, November 2005 (reaffirmed 2007).
6. Rodger, M.A., et al. Inherited Thrombophilias and Pregnancy Complications Revisited. Obstetrics and Gynecology, volume 112, number 2, August 2008, pages 320-324.
7. Bates, S.M., et al. Venous Thromboembolism, Thrombophilia, Antithrombotic Therapy, and Pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest, volume 133, number 6, June 2008 supplement, page 844S-886S.

July 2009