The prevalence and biologic significance of lupus anticoagulant and antic ardiolipin antibodies in a general obstetric population

doi:10.1016/0002-9378(89)90522-X

American Journal of Obstetrics and Gynecology

Volume 161, Issue 2, August 1989, Pages 369-373

https://doi.org/10.1016/0002-9378(89)90522-X Get rights and content

Circulating antibodies to negatively-charged phospholipids have been implicated in the genesis of adverse pregnancy outcomes. However, it has yet to be established that these antibodies are causative or that they are invariably associated with untoward perinatal outcomes. To address this issue, the prevalence of lupus anticoagulant and anticardiolipin antibodies was recorded in a low-risk obstetric population, and the outcomes of untreated pregnancies were evaluated. Two of 737 patients (0.27%) had lupus anticoagulant documented by a prolonged activated partial thromboplastin time that did not correct with mixing studies. In comparison, greatly elevated concentrations of immunoglobulin M-anticardiolipin antibodies or immunoglobulin G-anticardiolipin antibodies were identified in 16/737 (2.2%) patients by means of an enzyme-linked immunosorbent assay. Spontaneous abortions occurred in both lupus anticoagulant-positive patients, suggesting that the activated partial thromboplastin time used was a relatively insensitive but specific marker for antiphospholipid antibody-associated adverse pregnancy outcomes. In contrast, although 12 of 16 anticardiolipin antibodies-positive pregnancies were complicated by perinatal loss, preterm delivery, or fetal growth retardation, four patients had uncomplicated pregnancies. Moreover, the distribution of anticardiolipin antibodies concentrations in these four patients was not clustered among the lowest anticardiolipin antibodies values, and anticardiolipin antibodies concentrations correlated weakly with adverse outcomes. These findings suggest that antiphospholipid antibodies are related to adverse pregnancy outcomes in a complex fashion and that therapy is not always required for acceptable outcomes in patients without other risk factors.

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Cited by (340)

Changes of platelet count throughout pregnancy in women with antiphospholipid syndrome
2019, Journal of Reproductive Immunology
Antiphospholipid antibodies (aPL) activate several cell types, such as endothelial cells, monocytes, neutrophils, fibroblasts, trophoblasts and platelets, thus leading to thrombosis and obstetric complications in patients with antiphospholipid syndrome (APS). The aim of the present study was the longitudinal investigation of platelet count in women with APS. Additionally, platelet count in women with APS who developed preeclampsia during pregnancy were compared to women with APS and uncomplicated pregnancy for potential early detection of preeclampsia.
This longitudinal study included 65 women with APS, 38 women with preeclampsia and 84 women with normal pregnancies, where platelet count was determined every four weeks, starting in early pregnancy.
Platelet count was significantly lower in women with APS compared to women who developed preeclampsia and normal pregnancies starting at 12 weeks of gestation. The areas under the curve (AUC) for platelet count were 0.765 at 12 weeks of gestation (95% of CI of 0.634-0.896), 0.747 at 20 weeks (95% of CI of 0.600-0.894), 0.719 at 24 weeks (95% of CI of 0.555-0.882), respectively. The cut off points for platelets were 216 at 12-14 weeks of gestation, 226.5 at 20 weeks of gestation, and 163.5 at 24 weeks of gestation, respectively.
We demonstrated a significant lower platelet count in women with APS throughout gestation. Additionally, platelet count is significantly decreased in women with APS who developed preeclampsia. According to our results, platelet count seems to have a predictive value for the development of preeclampsia in these women.
Angiogenic factors in pregnancies of women with antiphospholipid syndrome and systemic lupus erythematosus
2018, Journal of Reproductive Immunology
Citation Excerpt :
These antibodies are associated with arterial and/or venous thromboses and with multiple adverse obstetric outcomes, such as early and recurrent fetal loss, preeclampsia (PE), intrauterine growth restriction (IUGR) and intrauterine fetal death (IUFD) (Miyakis et al., 2006). APS occurs as primary APS (PAPS) or as secondary APS (SAPS) when combined with other autoimmune diseases such as systemic lupus erythematosus (SLE) (Miyakis et al., 2006; Lockwood et al., 1989; Pattison et al., 1993; Galarza-Maldonado et al., 2011; Asherson and Cervera, 2014; Gómez-Puerta and Cervera, 2014). Systemic lupus erythematosus (SLE) is associated with an increased risk of adverse obstetric outcomes and increased lupus disease activity during pregnancy (Hochberg, 1997; Baer et al., 2011; Simard et al., 2017) Antiphospholipid antibodies are present in 20–40% of SLE patients (Levine et al., 2002).
An imbalance of angiogenic placental factors such as endoglin, soluble fms-like tyrosine kinase 1(sFlt-1) and placental growth factor (PlGF) has been implicated in the pathophysiology of preeclampsia. This study aimed to evaluate serum levels of sFlt-1, PlGF and endoglin in women with primary and secondary antiphospholipid Syndrome (APS) and systemic lupus erythematosus (SLE) longitudinally through pregnancy.
Serum levels of sFlt-1, PlGF and endoglin were measured prospectively at 4-week intervals (from gestational weeks 12–36) in 17 women with primary APS (PAPS), 18 women with secondary APS (SAPS), and 23 women with SLE.
6/17 (35%) of women with PAPS, 3/18 (17%) of women with SAPS, and 2/23 (9%) of women with SLE developed early-onset preeclampsia. Women who developed preeclampsia had significantly higher mean sFlt-1 and endoglin levels, higher sFlt-1/PlGF ratios, and lower mean PlGF-levels than women who did not. These changes became statistically significant at 12 weeks for sFlt-1, PlGF and endoglin.
Endoglin, sFlt-1 and PlGF are potential early screening parameters for the development of preeclampsia in pregnant women with autoimmune diseases like APS and SLE.
Epidemiology of the Antiphospholipid Syndrome
2017, Handbook of Systemic Autoimmune Diseases
Antiphospholipid antibodies (aPL) are implicated in approximately a quarter of a million thrombotic events in the United States annually. These antibodies, anticardiolipin, anti-β2 glycoprotein I, and the lupus anticoagulant, can be found in healthy subjects with an increased prevalence in older populations, in children, in infections, and with malignancies. The risk of thrombosis is highest with multiple high-titre antibodies and in those in whom the lupus anticoagulant is detected. Factors such as hypertension and smoking also contribute to the rate of thrombosis. In patients with systemic lupus erythematosus (SLE), the lupus anticoagulant is the strongest predictor of thrombosis, with a 50% 20-year risk. The most common manifestation of antiphospholipid syndrome is deep venous thrombosis. Stroke is the most common arterial event, and aPL are implicated most frequently in those under the age of 50. There are conflicting data regarding pregnancy morbidity and aPL. Whilst pregnancy loss appears to occur at a higher rate with aPL, the data on other pregnancy morbidity, such as preeclampsia and the HELLP syndrome, have not consistently shown an association. In SLE, aPL are common, with the prevalence of anticardiolipin antibodies being 46% and that of the lupus anticoagulant 26%. Thus, aPL occur at a low frequency in the general population and are implicated in many thrombotic events. The risk of thrombosis increases with the antibody titre, number and presence of the lupus anticoagulant, which is of particular importance in the prediction of thrombosis in SLE.
Collagen Vascular Diseases in Pregnancy
2016, Obstetrics: Normal and Problem Pregnancies
Thromboembolic Disorders in Pregnancy
2016, Obstetrics: Normal and Problem Pregnancies
Histopathology in the placentae of women with antiphospholipid antibodies: A systematic review of the literature
2015, Autoimmunity Reviews
Citation Excerpt :
Antiphospholipid antibodies (aPLs) are a heterogeneous group of autoantibodies that are found in 0–5% of the general population [1,2] and in up to 40% of women suffering from stillbirth and/or recurrent miscarriage [3–7]. Antiphospholipid antibodies are also significantly associated with preeclampsia, intrauterine growth restriction and premature birth [4,7–10] as well as arterial and venous thrombosis [11–14]. Antiphospholipid antibodies react with a complex antigen involving anionic phospholipids and phospholipid-binding proteins, such as β2 glycoprotein I.
Antiphospholipid antibodies (aPLs) are a heterogenous group of autoantibodies associated with recurrent miscarriage, stillbirth, foetal growth restriction and premature birth. The cause of obstetric morbidity in women with aPLs is not completely understood. Workers have attempted to understand the role of aPLs in obstetric morbidity by investigating the histopathology of placentae from aPL-positive women. However, it is unclear from these diverse, and at times contradictory reports what histopathological lesions are common in the placentae of women with aPLs. This systematic review was undertaken to generate a complete picture of the placental features associated with aPLs in an attempt to understand the pathological processes that occur in pregnancies affected by aPLs.
Pubmed, Scopus, Web of Science and Embase were searched on the 27th November 2014 using the keywords “placenta” OR “trophoblast” AND “antiphospholipid antibody” OR “antiphospholipid antibody syndrome”. Records that were relevant and eligible were qualitatively assessed and given a score out of 24.
Of the 1112 records that were retrieved from the systematic search, 34 records were eligible for review, and were qualitatively scored. Of the 44 histopathological features that were reported in 580 placentae from aPL-positive women, six features appeared to be more common in the placentae of aPL-positive women compared to control women, including: placental infarction, impaired spiral artery remodelling, decidual inflammation, increased syncytial knots, decreased vasculosyncytial membranes and the deposition of complement split product C4d.
Based on the evidence in this systematic review, a human placental aPL fingerprint has been proposed. The diversity of the human placental aPL fingerprint suggests that multiple pathological processes may occur in pregnancies affected by aPL.

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The prevalence and biologic significance of lupus anticoagulant and antic ardiolipin antibodies in a general obstetric population

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Am J Obstet Gynecol

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