How we diagnose the antiphospholipid syndrome (original) (raw)
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Obstetric and vascular antiphospholipid syndrome: same antibodies but different diseases?
Recurrent thrombosis and miscarriages are the main clinical manifestations of antiphospholipid syndrome (APS). Although most patients display both clinical signs, some patients can have isolated vascular or obstetric variants. Emerging data raise the question of whether obstetric and vascular APS are the same or different diseases. An important difference between the two conditions is that a thrombophilic state is a common feature in vascular APS, whereas clot occlusions of the decidual spiral arteries are seldom observed in obstetric APS, and infarctions are found in only one-third of APS placentae. Conversely, inflammation, which is undetectable in vascular APS, is frequently observed in the placentae of patients with obstetric APS and has been documented in the placentae of pregnant mice with fetal loss mediated by antiphospholipid antibodies. Attempts to identify different antibodies or epitopes responsible for the two clinical manifestations of APS have so far been unsuccessful. Possible mechanisms exist that might explain the development of the two clinical presentations, including the tissue distribution and expression level of the main target antigen of antiphospholipid antibodies, β2 glycoprotein I (β2GPI). The identification of the factors that promote the onset of either obstetric or vascular APS has important diagnostic and therapeutic implications.
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.
Gynecology Obstetrics & Reproductive Medicine
OBJECTIVE: Obstetric antiphospholipid antibody syndrome is clinically recognized by adverse obstetric outcomes. To determine which antibody level best corresponds to the risk of these clinical outcomes is difficult. Obstetric antiphospholipid antibody syndrome-like adverse obstetric outcomes with single (n=108) and repeat (n=79) documented antiphospholipid antibody titers were evaluated. STUDY DESIGN: Serum samples of 108 Obstetric antiphospholipid antibody syndrome cases and 50 healthy gestational matched controls with no history of thrombosis and congenital anomalies were subjected to testing for antiphospholipid antibodies with ELISA after the events. Of this obstetric antiphospholipid antibody syndrome group, only 79 cases underwent repeat testing within 12 weeks. Quantitative data were described by values and percentages at the levels of (>10) and (>40 U). RESULTS: By one documented antiphospholipid test, the mean values of anticardiolipin, and anti-β2 glycoprotein1 (aβ2GP1) of obstetric antiphospholipid antibody syndrome versus controls were significantly different (p<0.001). Of 79 women who came for repeat sampling, a total number of women with persistent antiphospholipid antibody positivity was only 43 (54.43%). The number of obstetric antiphospholipid antibody syndrome cases with >40 U of antiphospholipid antibody was only 8 (18.60%). CONCLUSION: Not all obstetric antiphospholipid antibody syndrome associated pregnancy morbidities may own high (>40U) antiphospholipid antibody titers, but low antiphospholipid antibodies (>10U) also accompany to this clinical picture. Obstetric antiphospholipid antibody syndrome should always be taken into account clinically prior to laboratory findings. Besides, long persistence of antiphospholipid-M positivity in these placenta-mediated disorders may make sense in terms of trophoblastic damage.
The association of antiphospholipid antibodies with intrauterine fetal death: A case–control study
Thrombosis Research, 2012
Introduction: Over the past few decades it has been recognized that antiphospholipid antibodies are associated with pregnancy loss. Other placenta-mediated pregnancy complications have also been associated with the presence of antiphospholipid antibodies. Most studies have measured antiphospholipid antibodies near the time of the event investigated. Objectives: To investigate the association of antiphospholipid antibodies and a history of intrauterine fetal death (IUFD) in a case-control design. Materials and methods: A case-control study of 105 women with a history of IUFD after 22 gestational weeks and 262 controls with live births. The prevalence of lupus anticoagulant, anticardiolipin-and anti-β2glycoprotein 1 antibodies were measured 3-18 years after the event of IUFD. Results: Total 9.5% of women with a history of IUFD and 5.0% of controls had at least one positive test for antiphospholipid antibodies (OR 2.0; 95% confidence interval (CI) 0.9-4.8). Women with a history of IUFD were significantly more often positive for lupus anticoagulant compared to controls (OR 4.3; 95% CI 1.0-18.4). The association of lupus anticoagulant with a history of IUFD was confined to women positive for other antiphospholipid antibodies in addition to lupus anticoagulant. Being positive for anti-β2-glycoprotein 1 or anticardiolipin antibodies alone was not significantly associated with a history of IUFD. Conclusions: Women with a history of IUFD after 22 gestational weeks were more often lupus anticoagulant positive. The association was confined to women with multiple positivity for antiphospholipid antibodies, although firm conclusions on the importance of multiple positivity cannot be made from this study.
Antiphospholipid antibodies in obstetrics: new complexities and sites of action
Human Reproduction Update
The antiphospholipid syndrome, the cause of which remains unknown, is characterized by severe pregnancy complications. Fetal losses have been attributed to thrombosis of the uteroplacental vasculature and placental infarction. Polyclonal and monoclonal antiphospholipid antibodies seem able to recognize a 'plasma cofactor' on the endothelial and trophoblast cell surfaces and to affect cell function, inducing a procoagulant state. Although thrombosis is observed frequently in the decidua and placentas of patients with antiphospholipid antibodies, this observation was not universal, nor present in a sufficient degree to account for the pregnancy loss associated with this syndrome. Recent observations have suggested that antiphospholipid antibodies decreased placental hormone production and trophoblast intercellular fusion and invasion, suggesting that many of the obstetric complications observed in the syndrome may be due to antiphospholipid antibody-induced trophoblast dysfunction. However, the complex antigens on the trophoblast surfaces are still to be characterized and correlated with clinical manifestation. It is clear that successful pregnancies with the syndrome are more likely to occur after maternal treatment. Although prednisone may still be needed to treat manifestations associated with autoimmune disorders, the use of heparin, together with low-dose aspirin, has replaced prednisone for treatment of pregnant women. Maternal treatment and careful monitoring of fetal well-being are mandatory in the management of these high-risk pregnancies.
Journal of autoimmunity, 2018
Antibodies against β2 glycoprotein I (anti-β2GPI) have been identified as the main pathogenic autoantibody subset in anti-phospholipid syndrome (APS); the most relevant epitope is a cryptic and conformation-dependent structure on β2GPI domain (D) 1. Anti-β2GPI domain profiling has been investigated in thrombotic APS, leading to the identification of antibodies targeting D1 as the main subpopulation. In contrast, scarce attention has been paid to obstetric APS, hence this study aimed at characterizing the domain reactivity with regards to pregnancy morbidity (PM). To this end, 135 women with persistently positive, medium/high titre anti-β2GPI IgG, without any associated systemic autoimmune diseases and at least one previous pregnancy were included: 27 asymptomatic carriers; 53 women with obstetric APS; 20 women with thrombotic APS; and 35 women with both thrombotic and obstetric complications. Anti-D1 and anti-D4/5 antibodies were tested using a chemiluminescent immunoassay and a res...
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.
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.
Antiphospholipid Syndrome during pregnancy: the state of the art
Journal of prenatal medicine, 2011
Obstetric complications are the hallmark of antiphospholipid syndrome. Recurrent miscarriage, early delivery, oligohydramnios, prematurity, intrauterine growth restriction, fetal distress, fetal or neonatal thrombosis, pre-eclampsia/eclampsia, HELLP syndrome, arterial or venous thrombosis and placental insufficiency are the most severe APS-related complication for pregnant women. Antiphospholipid antibodies promote activation of endothelial cells, monocytes and platelets, causing an overproduction of tissue factor and thromboxane A2. Complement activation might have a central pathogenetic role. These factors, associated with the typical changes in the hemostatic system during normal pregnancy, result in a hypercoagulable state. This is responsible of thrombosis that is presumed to provoke many of the pregnancy complications associated with APS. Obstetric care is based on combined medical-obstetric high-risk management and treatment with the association between aspirin and heparin. T...