New research identifies which women are at risk for pregnancy loss and, more importantly, which women are not at risk and, therefore, do not require treatment. Many women with antiphospholipid antibodies (aPLs) are being unnecessarily treated with anticoagulants, such as heparin, which can be costly and can cause bleeding and bone loss, according to researchers for the PROMISSE study, the nation’s largest ever study of pregnancy loss in lupus comparing the pregnancies of healthy controls and women with aPL, lupus, and aPL and lupus. (PROMISSE stands for Predictors of pRegnancy Outcome: bioMarkers In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus.)
Because phospholipids are highly exposed in the placenta, antiphospholipids, when present, concentrate there as well, explain the study authors. This can result in inflammation that leads to organ damage, which is a mechanism for pregnancy complications. Most women with repeat miscarriages are tested for aPLs, and up to 15% are positive. Almost all of these women are then treated with anticoagulants. There are no guidelines for which aPLs to test for to assess risk, and interlaboratory consistency of results is poor. Between 20% and 35% of women with lupus and aPL have pregnancy complications, according to the study authors.
There are 3 types of aPLs-lupus anticoagulant (LAC), anticardiolipin antibody (aCL), and antibody to Beta2-glycoprotein I (anti-Beta2GPI). Of the 144 patients with aPLs in this current analysis, 25 had adverse pregnancy outcomes.1 The strongest predictor of adverse pregnancy outcomes was LAC; 39% of patients for whom an LAC test was positive had adverse pregnancy outcomes, compared with 3% in patients who did not have LAC. Of those with aCLs but without LAC, 8% had an adverse pregnancy outcome. Neither aCL nor anti-Beta2GPI were associated with increased risk.
There are 3 screening assays able to detect LAC, but each test has considerable variability in specificity and sensitivity. Insurers rarely cover multiple tests for LAC, and laboratories generally only offer one type of test, explain the study authors. Therefore, clinicians must not rule out the presence of LAC even if the laboratory report shows a negative test result.
- Only women known to be positive for LAC should be treated with anticoagulants.
- After 12 weeks of gestation, the presence of lupus anticoagulant is the strongest predictor of adverse pregnancy outcomes.
- Despite a negative result on LAC testing, clinicians should retain a high level of concern if only 1 testing method was used. Any positive result for LAC is clear evidence of pregnancy risk.
1. Lockshin MD, Kim M, Laskin CA, et al. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but no anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum. 2012;64:2311-2318.