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Top 10 Series: Antiphospholipid Syndrome (APS) and Pregnancy

Top 10 Points to Optimize the Outcome

1. What is antiphospholipid syndrome?

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by production of antibodies – antiphospholipid antibodies (aPL) – that “attack” the person’s own body, resulting in blood clots and/or pregnancy complications. However, people who are aPL-positive, that is, those who produce aPL, may or may not develop clinical problems. A positive aPL test is not enough to diagnose APS.

The spectrum of aPL-positivity includes:

  • Asymptomatic aPL-positive patients - those with no history of  blood clots or pregnancy complications;
  • APS patients with pregnancy complications only;
  • APS patients with blood clots with or without pregnancy complications.


2. What is a “clinically significant antiphospholipid antibody profile?”

A clinically significant aPL profile means that the patient’s blood has tested positive multiple times (at least twice and 12 weeks apart) for one or more of the aPL tests below:

  • Lupus Anticoagulant (LA) Test;
  • Anticardiolipin Antibody (aCL)  IgG/M Moderate-to-High Levels; and/or
  • Anti-ß2-Glycoprotein-I Antibody (aß2GPI) IgG/M Moderate-to-High Levels.

Moderate-to-high levels of aCL and aß2GPI (especially higher than 40 units) correspond to an increased risk of an aPL-related event; lower levels are clinically less important (especially lower than 20 units). Patients who are positive for the LA test, especially in combination with a moderate to high level of aCL and/or aß2GPI, seem to have a higher likelihood of an aPL-related complication than those who are negative for the LA test.


3. Is it possible for antiphospholipid syndrome patients to have a successful pregnancy?

Although APS patients are more likely to develop pregnancy complications than are women in the general population, the current management approach allows the majority of women with APS to deliver healthy babies. (More than 80% will have live newborns and approximately 60% will not have any pregnancy complications). To increase the chance of a successful pregnancy, it is strongly advised that patients consult their rheumatologist and an obstetrician experienced in managing high-risk pregnancies prior to becoming pregnant. These specialists will review specific aPL-related pregnancy concerns and recommended treatments. Pregnant women with APS who have not sought this care in advance should arrange these appointments immediately.


4. What are the antiphospholipid antibody-related concerns during pregnancy?

Some of the aPL-related concerns in aPL-positive pregnant patients include:

  • Miscarriages, which can occur early (between conception and week nine of gestation) and recur early in subsequent pregnancies, or late in the pregnancy (between week ten of gestation and delivery).
  • Preterm delivery (before week thirty-seven of gestation) as a result of preeclampsia (high blood pressure and protein in the urine after week twenty of gestation), eclampsia (a severe form of preeclampsia that can also cause seizures and coma in the mother), or placental insufficiency (alternations in fetal well-being due to problems with the placenta)
  • Intrauterine growth restriction (fetuses that are smaller than expected).
  • Blood clots during pregnancy and up to six weeks following the birth of the baby (also referred to as the post-partum period).

It is important to note that:

  • aPL is not the only risk factor for the complications described above. Other causes, such as hormonal, anatomic, and genetic factors, should be investigated in all aPL-positive patients.
  • Some pregnancy complications are more specific for aPL: late miscarriages, recurrent early miscarriages, and early preeclampsia.


5. What are the medications commonly used for antiphospholipid syndrome patients during pregnancy?

Although controversial due to the limited number of well-designed controlled studies, the current standard of care for pregnant aPL-positive patients includes,

  • For APS patients with a history of pregnancy complications only: oral low-dose aspirin (LDA), which prevents clots by blocking platelet aggregation, and subcutaneous injections of prophylactic (low) dose heparin (an anticoagulant drug that prevents the clotting ability of the blood);
  • For APS patients with a history of a thrombotic vascular event regardless of pregnancy history: oral LDA and subcutaneous injections of therapeutic (high) doses of heparin;
  • For asymptomatic (no history of vascular or pregnancy events) patients with clinically significant aPL profiles: no treatment or oral LDA.

The risks and benefits, as well as the timing, of these general treatment recommendations should be discussed with an experienced physician. Treatment is usually started when the pregnancy is confirmed. In addition to the treatments described, calcium and vitamin D supplements can be prescribed to reduce the risk of heparin-induced osteoporosis (reduced bone strength). All these medications are safe for both the mother and the baby. An effective treatment for the minority of aPL-positive patients who fail LDA and heparin is still under investigation. Options should be discussed with an experienced physician.


6. What should antiphospholipid syndrome patients do during pregnancy?

After the pregnancy is confirmed, APS patients should be seen by their rheumatologist and obstetrician as soon as possible. The purpose of this visit is to assess the state of their health by means of a complete physical examination and blood tests. Throughout the pregnancy, regular visits (more frequently during the last third trimester), blood and urine tests, blood pressure measurements, and obstetrical ultrasound examinations are essential. Patients and their family members/caregivers should be familiar with the following symptoms which require immediate medical attention:

  • The early signs of a blood clot, including numbness, swelling, or sudden onset of pain in the legs and arms, as well as shortness of breath, chest pain, coughing blood or blood-streaked mucous, paralysis or weakness of the face or limbs, slurred speech, and visual changes.
  • The signs of increased protein in the urine, including foamy urine or swelling in hands, feet, or face.
  • The signs of thrombocytopenia (reduction of platelets–the component in blood that regulates clotting), which include bleeding from the mouth or the nose, bloody or dark stool, bloody urine, and bruising or red dots on the skin.
  • The signs of preeclampsia, which include high blood pressure, abdominal pain, nausea, vomiting, headache, and change in vision.

In addition to being ready to take prompt action should complications occur, APS patients should arrange to deliver their babies  at a hospital with a Neonatal Intensive Care Unit, and other advanced facilities to provide specialized care for APS patients and their babies as needed.


7. Is it possible for antiphospholipid syndrome patients to have a normal vaginal delivery?

If the mother and the baby are healthy at the time of labor, vaginal delivery is likely to be successful. However, if the mother and/or baby are under stress, or in the event of preterm labor, a caesarian section might be the safest and the fastest method of delivery. The management of medications, e.g., LDA and heparin, during the delivery should be discussed with the patient’s physician in advance.


8. What should mothers with antiphospholipid syndrome do after the delivery of the baby?

After the delivery, it is essential that APS patients follow up regularly with their rheumatologist to monitor their disease. Subcutaneous injections of heparin are recommended for 6-8 weeks after delivery to prevent blood clots (a prophylactic low dose for patients without history of blood clots; and a therapeutic high dose for patients with history of blood clots until warfarin is restarted). Special precautions, e.g. elastic compression stockings, and early mobilization, are critical for patients with a history of blood clots and for those who have had cesarean sections. Birth control options should be discussed with the gynecologist. Breastfeeding is not a reliable method of birth control and estrogen-containing birth control pills should not be used since they can heighten the chances of developing a clot.


9. Is it possible for a mother with antiphospholipid syndrome to breastfeed her baby?

Yes, most women with APS are able to breastfeed their babies. However, some medications can transfer through the breast milk into the baby. Non-steroidal anti-inflammatory medications (including LDA), acetaminophen, hydroxychloroquine, low-dose prednisone (less than 20 mg/day), warfarin, and heparin are safe during breastfeeding. If the daily dose of prednisone exceeds 20 mg, the mother should wait for about four hours after taking the medication before nursing the baby. Patients with APS and other autoimmune diseases may be on other immunosuppressive medications; they should avoid breastfeeding while on cyclophosphamide, methotrexate, or mycophenolate mofetil and discuss the risks and benefits with their physicians if they are on azathioprine or cyclosporine.


10. What effects can antiphospholipid syndrome have on the baby?

Most APS patients give birth to healthy babies; however these babies are prone to low birth weight. In some cases aPL may be detected in the baby’s blood at birth as a consequence of maternal transmission; however, the antibodies tend to disappear within the first six months and are usually do not result in blood clots.


Erkan D, Lally L, Lockshin MD. "What Should Patients Know About Antiphospholipid Antibodies and Antiphospholipid Syndrome?" In: Antiphospholipid Syndrome: Insights and Highlights from the 13th International Congress on Antiphospholipid Antibodies. Eds: Erkan and Pierangeli, Springer, 2012; 295-309.

Lockshin MD, Kim M, Laskin CA, Guerra M, Branch DW, Merrill J, Petri M, Porter TF, Sammaritano L, Stephenson MD, Buyon J, Salmon JE. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum. 2012;64:2311-2318

de Jesus GR, Agmon-Levin N, Andrade CA, Andreoli L, Chighizola CB, Flint Porter T, Salmon J, Silver RM, Tincani A, Ware Branch D. 14th International Congress on Antiphospholipid Antibodies Task Force Report on Obstetric Antiphospholipid Syndrome. Autoimmun Rev. 2014. pii:S1568-9972(14)00092-5.


Mara Taraborelli, MD

Visiting Rheumatology Fellow, Spedali Civili of Brescia, University of Brescia and Pavia, Brescia, Italy

Headshot of Doruk Erkan, MD, MPH
Doruk Erkan, MD, MPH
Associate Attending Rheumatologist, Hospital for Special Surgery
Associate Physician-Scientist, Barbara Volcker Center for Women and Rheumatic Disease

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