14th International Congress on Antiphospholipid Antibodies Task Force Report on Obstetric Antiphospholipid Syndrome (original) (raw)
Related papers
Pregnancy Morbidity in Antiphospholipid Syndrome: What Is the Impact of Treatment?
2014
Wo m e n w i t h p e r s is t e n t l y c ir c u l a t i n g antiphospholipid antibodies (aPL) have a higher incidence of recurrent abortions, fetal losses, pre-eclampsia, and placental insufficiency. Current treatment of patients with antiphospholipid syndrome (APS) during pregnancy with heparin and aspirin can act by preventing clot formation and improving live birth rates, but other obstetric morbidities remain high, especially in patients with a history of thrombotic events. In addition to the classical thrombotic placental events, other factors involving inflammation and complement activation seem to play a role in certain complications. In this article, we will review how medications interfere in the pathogenic mechanisms of APS, discuss the impact of current recommended treatment on pregnancy morbidity, and analyze new promising therapies.
Antiphospholipid antibodies and pregnancy loss: a disorder of inflammation
Journal of Reproductive Immunology, 2008
The antiphospholipid syndrome (APS) is a leading cause of miscarriage and maternal and fetal morbidity. APS is characterized by thrombosis and pregnancy loss that occur in the presence of antiphospholipid (aPL) antibodies. Using a mouse model of APS induced by passive transfer of human aPL antibodies, we have shown that complement activation plays an essential and causative role in pregnancy loss and fetal growth restriction, and that blocking activation of the complement cascade rescues pregnancies. Conventional treatment for APS patients is sub-anticoagulant doses of heparin throughout pregnancy. Could heparin prevent pregnancy loss by inhibiting complement? In our experimental model of APS, heparin inhibits activation of complement on trophoblasts in vivo and in vitro, and anticoagulation in and of itself is not sufficient to prevent pregnancy complications. These studies underscore the importance of inflammation in fetal injury associated with aPL antibodies and raise the importance of developing and testing targeted complement inhibitory therapy for patients with APS.
Updating on the Pathogenic Mechanisms 5 of the Antiphospholipid Antibodies-Associated Pregnancy Loss
Clinical Reviews in Allergy & Immunology, 2008
Anti-phospholipid antibodies (aPL) are risk factor for recurrent pregnancy loss and obstetrical complications. The mechanisms of aPL-mediated pregnancy failure are still a matter of research. Although aPL are associated with thrombosis, thrombotic events cannot explain all the miscarriages. There is evidence for a direct in vitro aPL effect on the trophoblast as shown by their binding; reduction of proliferation, human chorionic gonadotrophin release, in vitro invasiveness, adhesion molecule expression; and increased apoptosis. Such a direct reactivity is supported by the expression of beta2 glycoprotein (β2GP) I on trophoblast cell membranes. aPL/anti-β2GPI antibodies also bind to human decidual/endometrial cells in vitro and induce a pro-inflammatory phenotype. APL-mediated inflammatory processes at the placental level are apparently responsible for fetal loss at least in animal models. Both complement activation and pro-inflammatory cytokine/chemokine secretion have been shown to play a role. More recently, complement-induced tissue factor expression on infiltrating neutrophils was described as an additional pathogenic mechanisms mediated by aPL. As a whole, these findings do suggest that aPL may induce a defective placentation by acting at different levels without involving necessarily thrombotic events.
Predictors of Pregnancy Outcome in Antiphospholipid Syndrome: A Review
Clinical Reviews in Allergy & Immunology, 2010
In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk of preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In the last two decades, several studies were performed to identify the predictive role of some parameters in relation to obstetric outcome in APS patients. Among these, the uterine velocimetry Doppler is the most studied. It provides a noninvasive method for the study of uteroplacental blood flow, being able to detect a condition of impaired placental perfusion, due to the presence of circulating antiphospholipid antibodies (aPL). To date, the uterine artery Doppler velocimetry resulted to be a useful tool to identify APS pregnancies at higher risk of adverse pregnancy outcome. False-positive IgM for toxoplasmosis, others, rubella, cytomegalovirus, herpes viruses (TORCH) complex is associated to a worse pregnancy outcome because it reflects a dysregulation of the immune system which may amplify placental autoimmune damage. Moreover low levels of complement components are related to an increased incidence of obstetrical complications, suggesting that placental deposition of immune complexes and activation of complement cascade may contribute to placental failure APS related. The abnormal uterine Doppler velocimetry, falsepositive TORCH IgM and low levels of complement components can be considered prognostic indexes of poor pregnancy outcome in APS.
The Journal of Rheumatology, 2013
Objective.The effect of low-dose aspirin (LDA) on pregnancy outcome in antiphospholipid (aPL)-positive women not fulfilling the criteria for antiphospholipid antibody syndrome (APS) was evaluated retrospectively.Methods.We evaluated 139 pregnancies of 114 aPL-positive women not fulfilling the Sydney classification criteria for definite APS (104 treated with LDA, 35 untreated). Inclusion criteria consisted of (1) any titer of aPL and no previous pregnancy or no pregnancy losses (defined as aPL carriers); (2) any titer of aPL and 1 or 2 pregnancy losses before the 10th gestational week. No women had previous thrombosis. The rate of pregnancy loss, gestational age at delivery, and birth weight percentile were compared in the treated and untreated patients. Associations between clinical and laboratory characteristics and pregnancy outcomes were investigated.Results.The rate of pregnancy loss was low in both treated and untreated groups (7.7% vs 2.9%, respectively). There were no statist...
BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. Anticardiolipin antibodies (aCL), anti-β2 glycoprotein-I (ab2GPI) and lupus anticoagulant (LA) are the main autoantibodies found in APS. Despite the amassed body of clinical knowledge, the risk of obstetric complications associated with specific antibody profile has not been well established. OBJECTIVE: To assess the risk of obstetric complications in women with primary APS associated with specific antibody profile STUDY DESIGN: The PREGNANTS study is a multicenter, retrospective, cohort study. Diagnosis and classification of APS were based on the 2006 International revised criteria. All women included in the study had at least one clinical criteria for APS, were positive for at least one antiphospholipid antibodies (aCL, ab2GPI and/or LA), and were treated with low-dose aspirin and prophylactic low molecular weight heparin (LMWH) starting from the first trimester. Only singleton pregnancies with primary APS were included. The primary outcome was livebirth, defined as any delivery of a live infant after 22 weeks. The secondary outcomes were preeclampsia with and without severe features, intrauterine growth restriction (IUGR) and stillbirth. We planned to assess the outcomes associated with the various antibody profile (test result for LA, aCL and ab2GPI). RESULTS: There were 750 singleton pregnancies with primary APS in the study cohort. 54 (7.2%) were positive for LA only, 458 (61.0%) for aCL only, 128 (17.1%) for ab2GPI only; while 90 (12.0%) were double positive and LA negative and 20 (2.7%) were triple positive. The incidence of livebirth in each of these categories was 79.6%, 56.3%, 47.7%, 43.3%, and 30.0%, respectively. Compared to women with only one antibody positive test results, women with multiple antibody positive results had a significantly lower livebirth (40.9% vs 56.6%; aOR 0.71, 95% CI 0.51 to 0.90). Also, they were at increased risk of preeclampsia without (54.5% vs 34.8%; aOR 1.56, 95% CI 1.22 to 1.95) and with severe features (22.7% vs 13.8%, aOR 1.66, 95% CI 1.19 to 2.49), IUGR (53.6% vs 40.8%; aOR 2.31, 95% CI 1.17 to 2.61) and stillbirth (36.4% vs 21.7%; aOR 2.67, 95% CI 1.22 to 2.94). In women with only one positive test result, women with ab2GPI positivity present alone had a significantly lower livebirth (47.7% vs 56.3% vs 79.6%; p<0.01), and a significantly higher incidence of preeclampsia without (47.7% vs 34.1% vs 11.1%; p<0.01) and with severe features (17.2% vs 14.4% vs 0%; p=0.02), IUGR (48.4% vs 40.1% vs 25.9%; p<0.01) and stillbirth (29.7% vs 21.2% vs 7.4%; p<0.01) compared to women with aCL and to women with LA present alone, respectively. In the group of women with more than one antibody positivity, triple-positive women had lower livebirth (30% vs 43.3%; aOR 0.69, 95% CI 0.22 to 0.91), and higher incidence of IUGR (70.0% vs 50.0%; aOR 2.40, 95% CI 1.15 to 2.99) compared to double positive and LA negative women. CONCLUSION: In singleton pregnancies with primary APS, aCL is the most common sole antiphospholipid antibody present, but ab2GPI is the one associated with the lowest livebirth rate and highest incidence of preeclampsia, IUGR, and stillbirth, compared to presence of aCL or LA alone. Primary APS women have an increased risk of obstetric complications and lower livebirth when more than one antiphospholipid antibody is present. Despite therapy with low-dose aspirin and prophylactic LMWH, chance of a live-birth neonate is only 30% for triple-positive women.
To study the association of antiphospholipid syndrome in patients with bad obstetric history
International Journal of Reproduction, Contraception, Obstetrics and Gynecology
Background: Antiphospholipid antibodies (APLA) are the most important autoimmune cause of recurrent pregnancy loss (RPL). These pregnancies can be saved if diagnosed and treated adequately. This can be achieved by routine screening for APLA in pregnant women with a bad obstetric history (BOH) and unexplained fetal loss. Aims and Objective: To study the association of antiphosholipid antibodies in women with BOH and thus evaluating the usefulness of routine screening of serum antiphosholipid antibodies in patients with unexplained fetal wastage and BOH for better outcome.
Management of Obstetric Antiphospholipid Syndrome
Current Rheumatology Reports, 2012
Recurrent early miscarriages (excluding chromosomal anomalies), late fetal loss, and maternal thrombosis are characteristic of obstetric antiphospholipid syndrome (APS). Obstetric complications such as preeclampsia, fetal growth restriction, premature delivery, and fetal death also occur in higher frequency in APS patients than in the general population. A high-risk obstetric center is needed for proper evaluation of and intervention with pregnant women with APS. Association with lupus carries additional risk of thrombosis when antiphospholipid antibodies (aPLs) are present. Gestational results with live births are improved to about 80% when antithrombotic therapy is used, but failure in 20% to 30% of the cases despite correct treatment with lowdose aspirin with or without heparin reveals new pathways for pregnancy loss in APS and unmet needs. At the moment, there is no recommendation to investigate patients with infertility for the presence of aPLs.
Journal of SAFOG, 2022
Background: Antiphospholipid syndrome (APS) is one of the important treatable causes of bad obstetric history (BOH). The literature on the association between the presence of antiphospholipid antibodies (APLA) in patients with BOH and clinical parameters is limited. Aims and objectives: (1) To estimate the prevalence of APLA in patients with BOH and (2) To determine the association of APLA with various clinical parameters in patients with BOH. Materials and methods: A total of 80 patients with BOH of unknown etiology and 40 age-matched controls with at least 1 successful pregnancy outcome were clinically assessed and screened for the presence of APLA {anti-β2 glycoprotein-1-IgG (ABGP1-IgG); anticardiolipin IgG and IgM [anticardiolipin antibodies (ACLA), ACLA-IgG and-IgM)]; and lupus anticoagulant (LAC)}. The clinical parameters of APLA-positive and APLAnegative cases were compared. Results: Antiphospholipid antibodies were detected in 12 of 80 cases (15%) compared with none among controls [odds ratio (OR) = 29.38; 95% confidence interval (CI) = 1.71-505.4; p = 0.0199]. The antibody ABGP1-IgG was the commonest one (n = 7, 58.33%) followed by LAC (n = 4, 33.33%) and ACLA-IgG and-IgM (1 each). Patients with APLA-positive BOH had significantly increased incidence of thrombotic episodes (p = 0.01), hypertension (p = 0.05), thrombocytopenia p <0.01), and anemia (9.67 ± 1.75 vs 11.04 ± 1.37 gm/dL; p <0.01). Second-trimester abortion was significantly higher (p = 0.03), and first-trimester abortions were significantly lesser (p = 0.02) compared with patients with APLA-negative BOH. Third-trimester adverse obstetric events were comparable between the two groups. Conclusion: Antiphospholipid antibodies are present in 15% of patients with BOH of unknown etiology. History of thrombosis, hypertension, thrombocytopenia, anemia, and second-trimester abortions were significantly associated with the presence of APLA in BOH. Clinical significance: The findings from this study will help in determining the subset of patients with BOH who have higher likelihood of presence of APLA and therefore increase the chances of treatment and a successful pregnancy outcome.