Lupus anticoagulant affects pregnancy outcomes

Lupus Foundation of America

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What is the topic?

Antiphospholipid syndrome (APS) is a blood clotting disorder in which antibodies are made against proteins that help to control how fast or slowly the blood clots. Many people with lupus have APS, although it can occur without other features of lupus or in patients with other autoimmune diseases.

APS antibodies currently evaluated in clinical practice include lupus anticoagulant, anti-cardiolipin antibodies, and antibodies to β2-glycoprotein I. APS antibodies are thought to increase the risk of pregnancy complications, but many women with APS antibodies have normal pregnancies. Whether specific factors, such as having lupus, can predict which women with APS antibodies are more likely to experience pregnancy complications has not been fully established or agreed upon. Identification of specific APS antibodies that could predict adverse pregnancy outcomes in women with lupus would be very useful in clinical settings.

What did the researchers hope to learn?

The researchers hoped to learn about which APS antibodies confer increased risk for adverse pregnancy outcomes in women with APS, lupus, or both.

Who was studied?

144 pregnant women with APS (57 of which also had systemic lupus) and 274 pregnant women with lupus (but not APS) were included in the “Predictors of Pregnancy Outcomes: Biomarkers in APS and systemic lupus erythematous” (PROMISSE) Study.

How was the study conducted?

Pregnant women with APS, lupus, or both (as well as healthy pregnancy women) were followed monthly by an obstetrician and during each trimester by a rheumatologist, and delivered between September 2003 and March 2011. Blood samples were taken in order to measure lupus anticoagulant, anti-cardiolipin antibodies, and antibodies to β2-glycoprotein I at different times throughout pregnancies.

For the pregnant women to be included in the study, gestation had to be 12 weeks or earlier in women with lupus or normal women, or 18 weeks or earlier in women with APS. Healthy pregnant women were included unless they had known mental illness, prior fetal loss, more than one embryonic loss, or no previous successful pregnancies.

Inclusion criteria included: a) confirmed positivity for APS at two or more separate time points; b) live intra-uterine pregnancy confirmed by ultrasound; c) age 18-45 years; d) ability to give informed consent; and e) no significant anemia.

Exclusion criteria included: a) treatment with prednisone > 20 mg/day or significant protein in urine; b) evidence of inflammation in the urine; c) serum creatinine > 1.2 mg/dL; d) type I or II diabetes mellitus prior to pregnancy; e) hypertension at the screening visit; and f) multi-fetal pregnancy.

Adverse pregnancy outcome was defined as an otherwise unexplained fetal demise after 12 weeks, neonatal death prior to discharge, associated with complications of prematurity, pre-term delivery prior to 34 weeks, and small for gestational age (birth weight <5th percentile).

What did the researchers find?

Most of the women included in the study were white, at least 30 years old, and had a prior episode of thrombosis (a blood clot). More women included than not had systemic lupus erythematosus, although this did not consistently influence the likelihood of having adverse pregnancy outcomes in women with APS. The women included were either being treated with heparin or not being treated with this drug in relatively equal proportions. More women included than not were taking hydroxychloroquine or steroids.

Significantly more patients with APS antibodies (19%) had adverse pregnancy outcomes than did healthy pregnant women (2%). In addition, of the women with APS, significantly more (44%) had lupus anticoagulant (of whom 39% had adverse pregnancy outcomes) than not (3%). Of the women with anti-cardiolipin antibodies meeting a certain threshold, 29% had adverse pregnancy outcomes, while significantly fewer (12%) of those having anti-cardiolipin antibodies below the threshold level had adverse pregnancy outcomes. However, all of the anti-cardiolipin positive patients having adverse pregnancy outcomes also had lupus anticoagulant. Among women with anti-cardiolipin antibodies above the threshold, 8% of women not having lupus anticoagulant had adverse pregnancy outcomes, while significantly more (43%) having lupus anticoagulant had adverse pregnancy outcomes.

About 52% of patients with prior thrombosis had adverse pregnancy outcomes, while significantly fewer (13%) did not have adverse pregnancy outcomes. The following did not significantly influence whether or not APS-positive women had adverse pregnancy outcomes in a consistent manner: prior fetal loss, non-white race, presence of systemic lupus erythematosus, and treatment with steroids or hydroxychloroquine.

What were the limitations of the study?

This study included a relatively small number of non-white women, which may have made it difficult to detect consistent statistical differences in adverse pregnancy outcomes by ethnicity. In addition, the role of having had a prior thrombosis (blood clot) or having lupus anticoagulant may need to be further explored since they both increased the likelihood of having adverse pregnancy outcomes.

What do the results mean for you?

The occurrence of adverse pregnancy outcomes is increased in women with APS that have lupus anticoagulant and a history of thrombosis (blood clot). In some analyses, however, being older, or non-white, or having systemic lupus erythematosus increased the risk of having adverse pregnancy outcomes among women with APS.

Lupus anticoagulant, but not anticardiolipin antibody, predicts adverse pregnancy outcome in patients with antiphospholipid antibodies.
Lockshin MD, Kim M, Laskin CA, Guerra M, Branch DW, Merrill J, Petri M, Porter F, Sammaritano L, Stephenson MD, Buyon J, and Salmon JE. 
Arthritis & Rheumatism. 2012 Jan 24. doi: 10.1002/art.34402.