Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies
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OBJECTIVE: To investigate which serologic and clinical findings predict adverse pregnancy outcome in patients with antiphospholipid antibody (aPL) and to test the hypothesis that a pattern of clinical and serologic variables can identify women at highest risk of adverse pregnancy outcome. METHODS: Women enrolled in a multicenter prospective observational study of risk factors for adverse pregnancy outcome in patients with aPL (lupus anticoagulant [LAC], anticardiolipin antibody [aCL], and/or antibody to β2-glycoprotein I [anti-β2 GPI]) and/or systemic lupus erythematosus (SLE) were recruited for the present prospective study. Demographic, clinical, serologic, and treatment data were recorded at the time of the first study visit. The relationship between individual and combined variables and adverse pregnancy outcome was assessed by bivariate and multivariate analysis. RESULTS: Between 2003 and 2011 we enrolled 144 pregnant patients, of whom 28 had adverse pregnancy outcome. Thirty-nine percent of the patients with LAC had adverse pregnancy outcome, compared to 3% of those who did not have LAC (P<0.0001). Among women with IgG aCL at a level of ≥40 units/ml, only 8% of those who were LAC negative had adverse pregnancy outcome, compared to 43% of those who were LAC positive (P=0.002). IgM aCL, IgG anti-β2 GPI, and IgM anti-β2 GPI did not predict adverse pregnancy outcome. In bivariate analysis, adverse pregnancy outcome occurred in 52% of patients with and 13% of patients without prior thrombosis (P=0.00005), and in 23% with SLE versus 17% without SLE (not significant); SLE was a predictor in multivariate analysis. Prior pregnancy loss did not predict adverse pregnancy outcome. Simultaneous positivity for aCL, anti-β2 GPI, and LAC did not predict adverse pregnancy outcome better than did positivity for LAC alone. CONCLUSION: LAC is the primary predictor of adverse pregnancy outcome after 12 weeks' gestation in aPL-associated pregnancies. Anticardiolipin antibody and anti-β2 GPI, if LAC is not also present, do not predict adverse pregnancy outcome.
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LA is the best-established risk factor for clinical manifestations related to antiphospholipid syndrome.
“LA is the best-established risk factor for APS-related clinical manifestations.[5][6][7][8][9]”
From Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis (2020) · cites this paper as [7]
The Discussion identifies lupus anticoagulant (LAC) as the primary predictor of adverse pregnancy outcome among patients with antiphospholipid antibodies. The study addresses pregnancy outcomes, not APS-related clinical manifestations generally, so it does not establish LA as the best-established risk factor for the broader claim. Page numbers were not provided in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredaCL are generally regarded as less symptomatic than LA or aB2GPI.
“which implies that aCL are generally regarded as less symptomatic than their conventional aPL counterparts.”
From Single or triple positivity for antiphospholipid antibodies in “carriers” or symptomatic patients: Untangling the knot (2021) · cites this paper as [7]
The Results and Discussion report that lupus anticoagulant (LAC) predicts adverse pregnancy outcomes more strongly than aCL in the pregnant patients studied. They do not place aCL below anti-β2-GP-I: both failed to predict adverse pregnancy outcomes without LAC. The study also concerns pregnancy outcomes, not symptoms generally. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn the literature, among aPL, isolated LA and aB2GPI are generally found to be associated with higher thrombotic risk than aCL.
“In the literature, 5- 8 among the aPL, isolated LA and aB2GPI are generally found to be associated with higher thrombotic risk than aCL.”
From Single or triple positivity for antiphospholipid antibodies in “carriers” or symptomatic patients: Untangling the knot (2021) · cites this paper as [7]
The Results and Discussion (page not provided) find that lupus anticoagulant predicts adverse pregnancy outcomes more strongly than anticardiolipin antibody. They do not establish higher thrombotic risk, and anti-β2-glycoprotein I did not predict adverse pregnancy outcomes in this study. Prior thrombosis is examined as a predictor of pregnancy outcome, not as an outcome compared across antibody types. (LLM, conf=0.84)
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- Authors
- Lockshin, M. D., Kim, M., Laskin, C. A., Guerra, M., Branch, D. W., Merrill, J., Petri, M., Porter, T. F., Sammaritano, L., Stephenson, M. D., Buyon, J., & Salmon, J. E.
- Affiliations
- Hospital for Special Surgery (US)
- Albert Einstein College of Medicine (US)
- University of Toronto (CA)
- Intermountain Healthcare (US)
- Oklahoma Medical Research Foundation (US)
- Johns Hopkins University (US)
- University of Utah (US)
- University of Chicago (US)
- New York University (US)
- ORCID
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2012-06-26
- Volume
- 64
- Issue
- 7
- Pages
- 2311-2318
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- PMC
- PMC3357451
- OpenAlex
- W2039200195
- Cited by
- 388
- References
- 34
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 35 · 2023: 21 · 2022: 26 · 2021: 23 · 2020: 31 · 2019: 29 · 2018: 25 · 2017: 28 · 2016: 35 · 2015: 27 · 2014: 38 · 2013: 26 · 2012: 9
- FWCI
- 24.51
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR049772)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- lupus anticoagulant, anticardiolipin antibodies, antiphospholipid antibodies, adverse pregnancy outcomes, systemic lupus erythematosus, anti-beta2-glycoprotein I antibodies, thrombosis, miscarriage, risk prediction, antiphospholipid syndrome
- MeSH terms
- Adult, Female, Humans, Predictive Value of Tests, Pregnancy, Pregnancy Complications, Pregnancy Outcome, Prospective Studies, Risk Factors, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome, Antibodies, Anticardiolipin
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