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:
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:
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.
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.
Some of the aPL-related concerns in aPL-positive pregnant patients include:
It is important to note that:
Although controversial due to the limited number of well-designed controlled studies, the current standard of care for pregnant aPL-positive patients includes,
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.
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:
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.
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.
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.
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.
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.