Search

Lupus anticoagulant (LA) is a well-established risk factor for the clinical manifestations of antiphospholipid syndrome (APS). Accurate LA detection is an essential prerequisite for optimal diagnosis and management of patients with APS or aPL carriers. Variability remains a challenge in LA testing, with reliable detection influenced by multiple factors, including pre-analytical conditions, anticoagulation treatment, choice of tests and procedures performed, as well as interpretation of results, that can lead to false-positives or negatives. A standardised approach to LA testing, following current guidance, based on published data and international consensus, and with attention to detail, is required to underpin accurate detection of LA. Future work should focus on better characterisation of the nature of LA, which may ultimately lead to improved diagnosis and management of patients with APS and aPL carriers. This article reviews current practice and challenges, providing an overview on detection of LA. [ABSTRACT FROM AUTHOR]

The role of antiphospholipid antibodies (aPL), which are not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood. The aim of this study was to determine the clinical significance of IgG antibodies for domain 1 of β2-glycoprotein 1 (β2-GP1), IgG anti-β2-GP1DI, in patients with APS with and without SLE. The study included 187 patients with APS with or without SLE, 49 patients formed the comparison group, and 100 apparently healthy individuals formed the control group. IgG/IgM antibodies to cardiolipin (aCL) and IgG/IgM anti-β2-GP1 were determined by enzyme immunoassay (ELISA) in patients with or without APS, and IgG anti-β2-GP1DI was determined by chemiluminescence assay (CLA) in all patients and controls. IgG anti-β2-GP1DI was detected in 37 (71%) of 52 patients with primary APS (PAPS), in 6 (50%) of 12 patients with probable APS, in 42 (71%) of 59 patients with SLE + APS, in 17 (26%) of 64 patients with SLE, in 1 (2%) of the comparison group, and in none of the control group. IgG anti-β2-GP1DI was significantly associated with PAPS and SLE + APS compared with the patients with SLE (p = 0.0002 and 0.0001, respectively). The association of IgG anti-β2-GP1DI with clinical manifestations of APS (thrombosis (p = 0.001) and obstetric pathology (p = 0.04)) was detected. There was a significant association of IgG anti-β2-GP1DI with arterial thrombosis (p = 0.002) and with late gestational obstetric pathology (p = 0.01). High specificity of IgG anti-β2-GP1DI depending on the diagnosis and clinical manifestations of APS despite low sensitivity was noted: specificity was 84% for thrombosis, 94% for obstetric pathology, and 89% for APS. Isolated IgG anti-β2-GP1DI positivity was reported in 2% of 50 aPL-negative patients and was not associated with APS manifestations. The frequency of IgG anti-β2-GP1DI detection was higher in the patients with APS compared to the patients with SLE, comparison group, and control (p < 0.05). Positive IgG anti-β2-GP1DI values were significantly associated with thrombotic complications and with obstetric pathology (p = 0.002 and p = 0.01, respectively). Specificity of IgG anti-β2-GP1DI for APS and its clinical manifestations (thrombosis and obstetric pathology) was higher than sensitivity (89, 94, and 84%, respectively). [ABSTRACT FROM AUTHOR]

Background: The presence of antiphospholipid antibodies (aPLs) plays a pivotal role in the pathogenesis of antiphospholipid antibody syndrome (APS). This study aimed to examine the diagnostic value of a set of non−criteria aPLs and their relevance with APS-related criteria and extra-criteria manifestations. Methods: From a prospectively constructed database, consecutive APS patients consisting of 114 primary APS (PAPS group), 54 with APS secondary to SLE (SAPS group), 9 seronegative APS (SNAPS), as well as 209 patients with systemic lupus erythematosus (SLE) and 88 healthy controls were included in this study. Levels of criteria aPLs, baseline information, and APS-related criteria and extra-criteria features were extracted from the database. Serum levels of non-criteria aPLs including aPC IgG/IgM, aPI IgG/IgM, aPE IgG/IgM/IgA, aPG IgG/IgM/IgA, anti-phosphatidic acid (aPA) IgG/IgM, aSM IgG/IgM, and aPS/PT IgG/IgM were analyzed with AESKULISA® ELISA Test Kits. Results: The addition of aPC IgG/M, aPI IgG/M, aPE IgG/M/A, aSM IgG/M, and aPA IgG/M to aCL or aβ2GPI IgG/M could significantly increase diagnostic sensitivity and accuracy. A significant difference between PAPS or SAPS and HC was presented in all non-criteria aPLs except for aSM IgM and aPG IgA. Eight out of nine SNAPS patients were positive for at least 1 aPL. Pregnancy morbidity was associated with aSM IgM (r = 0.22) and aSM IgG (r = 0.15). Pre-eclampsia or premature birth was associated with aSM IgG (r = 0.16), aPI IgG (r = 0.22), aPC IgG (r = 0.16), and aPG IgG (r = 0.18). Stroke was associated with aPI IgG (r = 0.2). The clinical association was also observed in DVT with aPS/PT IgG (r = 0.17). Valve lesion was positively associated with aSM IgM (Fisher test p = 0.039), APS nephropathy was associated with aPC IgG (OR 3.797), and livedo reticularis was associated with aPE IgM (OR 15.391). Conclusion: Additional detection of non-criteria aPLs including aPC IgG/M, aPE IgG/M/A, aPI IgG/M, aSM IgG/M, and aPA IgG/M could assist in APS diagnosis. The positivity of certain aPLs was statistically associated with both criteria and extra-criteria APS clinical manifestations. [ABSTRACT FROM AUTHOR]

The study of antiphospholipid antibodies (aPL), not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood.The aim of this study – to determine the clinical significance of IgG antibody testing for domain I β2 -glycoprotein 1 (β2 -GP1DI) – IgG anti-β2 -GP1DI in patients with APS with and without SLE.Materials and methods. The study included 187 patients with APS with or without SLE, 49 patients formed a comparison group, and 100 relatively healthy individuals formed a control group. IgG/IgM antibodies to cardiolipin and IgG/ IgM anti-β2 -GP1 were determined by enzyme immunoassay (ELISA) in patients with or without APS, and IgG antiβ2 -GP1DI was determined by chemiluminescence assay in all patients and controls.Results. IgG anti-β2 -GP1DI was detected in 37 (71%) of 52 patients with primary APS (PAPS), in 6 (50%) of 12 patients with probable APS, in 42 (71%) of 59 patients with SLE+APS, in 17 (26%) of 64 patients with SLE, in 1 (2%) of comparison group and in none of control group. IgG anti-β2 -GP1DI was significantly associated with PAPS and SLE+APS compared with patients with SLE (p=0.0002 and p=0.0001, respectively). The association of IgG anti-β2 -GP1DI with clinical manifestations of APS (thrombosis (χ2 =9.69; p=0.001) and obstetric pathology (χ2 =4.19; p=0.04)) was detected. There was a significant association of IgG anti-β2 -GP1DI with arterial thrombosis (χ2 =8.84; p=0.002) and with late gestational obstetric pathology (χ2 =6.35; p=0.01). High specificity of IgG anti-β2 - GP1DI depending on the diagnosis and clinical manifestations of APS was noted despite low sensitivity: specificity for thrombosis was 84%, for obstetric pathology – 94%, for APS – 89%. Isolated IgG anti-β2 -GP1DI positivity was reported in 2% of 50 aPL negative patients and was not associated with APS manifestations.Conclusion. The frequency of IgG anti-β2 -GP1DI detection was higher in patients with APS compared to patients with SLE, comparison group and control (p˂ 0.05). Positive IgG anti-β2 -GP1DI values were significantly associated with thrombotic complications and with obstetric pathology (χ2 =8.84; p=0.002 and χ2 =6.35; p=0.01). Specificity of IgG anti-β2 -GP1DI for APS and its clinical manifestations (thrombosis and obstetric pathology) was higher than sensitivity: 89%, 94%, and 84%, respectively.

• The antiphospholipid antibodies could result in inflammation, thrombosis and obstetric complications. • Lupus anticoagulant is actually a function test of antiphospholipid antibodies and brings stronger risk for thrombosis and pregnancy complications. • The phospholipid-dependent clotting time were significantly prolonged in anti-phosphatidylserine/prothrombin complex antibodies positive patients, and closely related to the anti-phosphatidylserine/prothrombin complex antibodies titres. • The positivity of anti-phosphatidylserine/prothrombin complex antibodies IgG showed significant association with thrombosis in the presence of lupus anticoagulant. Lupus anticoagulants (LA) increase the risk of thrombotic and obstetric events in patients with antiphospholipid syndrome than in those with other antiphospholipid antibodies. Anti-phosphatidylserine/prothrombin (aPS/PT) complex antibodies are thought to cause LA positivity. Therefore, we aimed to explore whether aPS/PT antibodies could prolong phospholipid (PL)-dependent clotting time and increase the risk of thrombosis or pregnancy complications based on LA positivity. We recruited 222 patients with positive LA and estimated their aPS/PT, anticardiolipin (aCL), anti-β2-glycoprotein I (aβ2GPI), and anti-β2GPI domain I (anti-D1) antibody (IgM and IgG) titers and PL-dependent clotting time. PT was longer in aPS/PT IgG-positive patients than in aPS/PT IgM-negative patients (P < 0.001), while there was no significant difference between aPS/PT IgM-positive and IgM-negative patients (P = 0.100). Both SCT-S and dRVVT-S were prolonged in aPS/PT (IgG and IgM)-positive patients compared to aPS/PT-negative patients (P < 0.001, P = 0.010, P < 0.001, P = 0.002, respectively). Similarly, the associations between aPS/PT IgG or IgM antibody titers and SCT-S or dRVVT-S were significant. SCT-C and dRVVT-C did not show any significant differences. The incidence of thrombosis in the aPS/PT IgG-positive group was much higher than that in the IgG-negative group (P = 0.012). Likewise, the incidence of thrombosis was higher in the anti-D1- and aPS/PT IgG-positive patients than in the negative controls (40 % vs 14.3 %, χ2 = 3.934, P = 0.047). Furthermore, the aPS/PT IgG-positive group showed the strongest association with thrombosis [OR 2.584, 95 % CI (1.213, 5.505)]. The aPS/PT antibodies prolonged PL-dependent clotting time, especially SCT-S and dRVVT-S. In addition, the presence of aPS/PT IgG antibodies increased the risk of thrombosis in LA positivity. [ABSTRACT FROM AUTHOR]

Background: At the beginning of the SARS-CoV-2 pandemic, there was a lack of information about the infection's impact on pregnancy and capability to induce de novo autoantibodies. It soon became clear that thrombosis was a manifestation of COVID-19, therefore the possible contribution of de novo antiphospholipid antibodies (aPL) raised research interest. We aimed at screening SARS-CoV-2 positive pregnant patients for aPL. Methods: The study included consecutive pregnant women who were hospitalized in our Obstetric Department between March 2020 and July 2021 for either a symptomatic SARS-CoV-2 infection or for other reasons (obstetric complications, labour, delivery) and found positive at the admission nasopharyngeal swab. All these women underwent the search for aPL by means of Lupus Anticoagulant (LA), IgG/IgM anti-cardiolipin (aCL), IgG/IgM anti-beta2glycoprotein I (aB2GPI). Data about comorbidities, obstetric and neonatal complications were collected. Results: 151 women were included. Sixteen (11%) were positive for aPL, mostly at low titre. Pneumonia was diagnosed in 20 women (5 with positive aPL) and 5 required ICU admission (2 with positive aPL). Obstetric complications occurred in 10/16 (63%) aPL positive and in 36/135 (27%) negative patients. The occurrence of HELLP syndrome and preeclampsia was significantly associated with positive aPL (p=0,004). One case of maternal thrombosis occurred in an aPL negative woman. aPL positivity was checked after at least 12 weeks in 7/16 women (44%): 3 had become negative; 2 were still positive (1 IgG aB2GPI + IgG aCL; 1 IgM aB2GPI); 1 remained positive for IgG aCL but became negative for aB2GPI; 1 became negative for LA but displayed a new positivity for IgG aCL at high titre. Conclusions: The frequency of positive aPL in pregnant women with SARSCoV-2 infection was low in our cohort and similar to the one described in the general obstetric population. aPL mostly presented as single positive, low titre, transient antibodies. The rate of obstetric complications was higher in aPL positive women as compared to negative ones, particularly hypertensive disorders. Causality cannot be excluded; however, other risk factors, including a full-blown picture of COVID-19, may have elicited the pathogenic potential of aPL and contributed themselves to the development of complications. [ABSTRACT FROM AUTHOR]

BackgroundAt the beginning of the SARS-CoV-2 pandemic, there was a lack of information about the infection’s impact on pregnancy and capability to induce de novo autoantibodies. It soon became clear that thrombosis was a manifestation of COVID-19, therefore the possible contribution of de novo antiphospholipid antibodies (aPL) raised research interest. We aimed at screening SARS-CoV-2 positive pregnant patients for aPL.MethodsThe study included consecutive pregnant women who were hospitalized in our Obstetric Department between March 2020 and July 2021 for either a symptomatic SARS-CoV-2 infection or for other reasons (obstetric complications, labour, delivery) and found positive at the admission nasopharyngeal swab. All these women underwent the search for aPL by means of Lupus Anticoagulant (LA), IgG/IgM anti-cardiolipin (aCL), IgG/IgM anti-beta2glycoprotein I (aB2GPI). Data about comorbidities, obstetric and neonatal complications were collected.Results151 women were included. Sixteen (11%) were positive for aPL, mostly at low titre. Pneumonia was diagnosed in 20 women (5 with positive aPL) and 5 required ICU admission (2 with positive aPL). Obstetric complications occurred in 10/16 (63%) aPL positive and in 36/135 (27%) negative patients. The occurrence of HELLP syndrome and preeclampsia was significantly associated with positive aPL (p=0,004). One case of maternal thrombosis occurred in an aPL negative woman. aPL positivity was checked after at least 12 weeks in 7/16 women (44%): 3 had become negative; 2 were still positive (1 IgG aB2GPI + IgG aCL; 1 IgM aB2GPI); 1 remained positive for IgG aCL but became negative for aB2GPI; 1 became negative for LA but displayed a new positivity for IgG aCL at high titre.ConclusionsThe frequency of positive aPL in pregnant women with SARS-CoV-2 infection was low in our cohort and similar to the one described in the general obstetric population. aPL mostly presented as single positive, low titre, transient antibodies. The rate of obstetric complications was higher in aPL positive women as compared to negative ones, particularly hypertensive disorders. Causality cannot be excluded; however, other risk factors, including a full-blown picture of COVID-19, may have elicited the pathogenic potential of aPL and contributed themselves to the development of complications.

Testing for antiphospholipid syndrome was incomplete in 23%, most frequently due to the omission of anti- 2GPI antibodies.110 A systematic review of 5217 stroke patients and matched controls from 43 studies investigated the presence of antiphospholipid antibodies in young patients (<50 years) with stroke.122 Overall, 17.2% of patients with stroke and 11.7% with transient ischaemic attack (TIA) had antiphospholipid antibodies. Analysis of data from pooled incidence-cases found that in 19% of patients, splanchnic vein (hepatic, mesenteric, portal, splenic, inferior vena cava) thrombosis preceded the diagnosis of PNH.87 For the remaining patients, visceral thrombosis occurred at a median of 5 years (range, 0-24) after diagnosis. Similarly, a retrospective review of 752 tests in 82 stroke patients yielded 56 positive tests in 42 patients but thrombophilia was confirmed in only three patients, and management changed in only one.112 An audit of acute post-stroke thrombophilia testing highlighted the high cost and low yield. Thrombosis in unusual sites Investigation and management of thrombosis at unusual sites are discussed in another BSH Guideline.84 For thrombosis at unusual sites, which often involves local or systemic conditions triggering the event, testing for thrombophilia should be reserved for selected patients with unexplained events. [Extracted from the article]

This is a case report of women with pregnancy morbidity (PM), some of them associated with antiphospholipid syndrome (APS), in which the glycan patterns of immunoglobulin G (IgG) were investigated based on the theory of alteration of glycosylation in autoimmunity. We used lectin blot to determine changes in terminal glycosylation of polyclonal IgG from women with antiphospholipid (aPL) antibodies and PM plus vascular thrombosis (PM/VT) and seronegative-obstetric APS (SN-OAPS). In addition, we analyzed IgG from women with PM without aPL (PM/aPL-) and healthy women, as controls. Even though the SN-OAPS and PM/VT groups share the PM, only the SN-OAPS group showed a decreased expression of galactose compared to the healthy group. We also found the presence of mannosylated oligosaccharides in IgG from all patients being significantly higher in IgG from women of the PM/aPL- group. The differences in glycans presented here could relate to pathological mechanisms of PM associated with APS.

The antiphospholipid syndrome is an autoimmune disease characterized by thrombosis and pregnancy morbidity. The manifestations are caused by antibodies targeting cell membrane phospholipids and/or associated proteins. The triggers leading to these antibodies' production are unknown but recent work suggests cross-reactivity between the autoantigens and peptides produced by the intestinal microbiome. Work on how the autoantibodies could cause clinical manifestations implicates different mechanisms. Binding to surface proteins of different cell types can induce intracellular signaling leading to cell activation and tissue factor expression. Complement activation and neutrophil extracellular-traps are also involved, and recent evidence implicates endothelial protein C receptor-lysobisphosphatidic acid complex. Pregnancy is a high-risk situation for antiphospholipid syndrome patients due to the increased risk of thrombosis and obstetric complications. Epidemiological and clinical research on APS is hampered by heterogeneity in populations, testing and treatment strategies. About one in 10 to one in fifty APS pregnancies is complicated by thrombosis, despite treatment. Pregnant patients with prior thrombosis are prescribed therapeutic dose heparins and low dose aspirin. Without prior thrombosis a prophylactic dose is used. The most frequent obstetrical manifestation is recurrent early pregnancy loss. The association of APS antibodies with late pregnancy loss is stronger, however. Prevention of recurrence is achieved with aspirin and prophylactic dose heparin, although the evidence is of low certainty. The third obstetrical classifying manifestation comprises preterm delivery due to placenta-mediated complications and is treated in subsequent pregnancies with aspirin with or without prophylactic dose heparin, again based on low quality evidence. New therapies are under investigation.

Antibodies to phospholipids (aPL) and associated proteins are a hallmark in the diagnosis of anti-phospholipid syndrome (APS). Those included in the classification criteria are the lupus anticoagulant (LA) and the IgG and IgM isotypes of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (β2GPI) antibodies. Non-classification criteria markers such as autoantibodies that recognize the phosphatidylserine/prothrombin (aPS/PT) complex have been proposed as biomarkers for APS. Studies of aPS/PT antibodies have shown a strong correlation to clinical manifestations and LA. We aimed to study the value and the persistence of aPS/PT IgG and IgM antibodies in a cohort of consecutive patients with clinical suspicion of APS and their utility as thrombotic risk markers. Our study, with 103 patients, demonstrates that persistently positive results for aPS/PT IgG antibodies were significantly associated with APS classification, thrombosis, triple aPL positivity, LA positive result, and the Global APS Score (GAPSS) > than 9 points (p < 0.01, for each condition). On the other hand, no association was seen with pregnancy morbidity (p = 0.56) and SLE (p = 0.07). Persistence of aPS/PT antibodies, defined according to the current laboratory classification criteria, likely improves the diagnosis and clinical assessment of patients with APS.

Antibodies to phospholipids (aPL) and associated proteins are a hallmark in the diagnosis of anti-phospholipid syndrome (APS). Those included in the classification criteria are the lupus anticoagulant (LA) and the IgG and IgM isotypes of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (β2GPI) antibodies. Non-classification criteria markers such as autoantibodies that recognize the phosphatidylserine/prothrombin (aPS/PT) complex have been proposed as biomarkers for APS. Studies of aPS/PT antibodies have shown a strong correlation to clinical manifestations and LA. We aimed to study the value and the persistence of aPS/PT IgG and IgM antibodies in a cohort of consecutive patients with clinical suspicion of APS and their utility as thrombotic risk markers. Our study, with 103 patients, demonstrates that persistently positive results for aPS/PT IgG antibodies were significantly associated with APS classification, thrombosis, triple aPL positivity, LA positive result, and the Global APS Score (GAPSS) > than 9 points (p < 0.01, for each condition). On the other hand, no association was seen with pregnancy morbidity (p = 0.56) and SLE (p = 0.07). Persistence of aPS/PT antibodies, defined according to the current laboratory classification criteria, likely improves the diagnosis and clinical assessment of patients with APS. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Ankara University Faculty of Medicine / Ankara Üniversitesi Tip Fakültesi Mecmuasi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Antiphospholipid syndrome (APS) is characterized by thrombosis (which may be venous, arterial, or microvascular) and/or pregnancy morbidity in association with persistently positive antiphospholipid antibodies. Although thrombosis and pregnancy morbidity are the main clinical criteria for a diagnosis of APS in the revised Sapporo (Sydney) criteria, recently published American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for APS have significantly refined the diagnostic algorithm to include a scoring system clustered into 6 clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular thrombosis, obstetric, cardiac valve, and hematologic). Diagnosis of APS is complicated by the fact that significant heterogeneity exists in patients' clinical presentation, underlying vascular risk factors, and methods of detecting antiphospholipid antibodies. Despite the autoimmune nature of APS, anticoagulation remains the main strategy for secondary prevention of thrombosis. Furthermore, optimal antithrombotic treatment in APS patients with arterial thrombosis remains controversial due to a paucity of data from randomized controlled studies. In this paper, we present 2 cases and highlight the diagnostic and therapeutic challenges they pose and how we approach them in the light of current evidence., Competing Interests: Declaration of competing interests J.E.M. has no conflict of interest to declare. D.J.A. received funding from Bayer plc and from LEO Pharma for research outside this project., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This is a case report of women with pregnancy morbidity (PM), some of them associated with antiphospholipid syndrome (APS), in which the glycan patterns of immunoglobulin G (IgG) were investigated based on the theory of alteration of glycosylation in autoimmunity. We used lectin blot to determine changes in terminal glycosylation of polyclonal IgG from women with antiphospholipid (aPL) antibodies and PM plus vascular thrombosis (PM/VT) and seronegative-obstetric APS (SN-OAPS). In addition, we analyzed IgG from women with PM without aPL (PM/aPL-) and healthy women, as controls. Even though the SN-OAPS and PM/VT groups share the PM, only the SN-OAPS group showed a decreased expression of galactose compared to the healthy group. We also found the presence of mannosylated oligosaccharides in IgG from all patients being significantly higher in IgG from women of the PM/aPL-group. The differences in glycans presented here could relate to pathological mechanisms of PM associated with APS. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome is a organized autoimmune disease presented with vascular thrombosis and pregnancy morbidity. The Sapporo classification criteria of APS were revised in 2006 and are used as the main diagnosis guideline, which validity as standard measurements is still in debate. This study observe the clinical and laboratory indices of APS among Saudi patients. This is a retrospective study hospital-based population. The clinical and Laboratory manifestations of diagnosed APS patients from electronical medical records identifies by ICD-9 code 795.79 in the King Saud University Medical City, Riyadh, Saudi Arabia, between 1990 and 2012. We selected patients with ICD-9 code 795.79 as. Sapporo criteria applied to all patients, then divided into cases fulfilled criteria and cases failed the criteria. To notice the difference in clinical and laboratory indices and comorbidities between the two groups, the T-test was performed and Logistic regression for the fulfilled criteria and clinical indices of vascular thrombosis, DVT/PE, recurrent, and pregnancy morbidity. A total of 72 (90%) females and 8 (10%) males, with the female-to-male ratio 9:1. The mean (±SD) age at diagnosis was 28.1 (±8.7) years (range 11–63 years). There were 22 patients (27.5%) attained the revised criteria (APS confirmed) and no significant difference between the two groups was observed (p > 0.2). However, we found Sapporo confirmed APS cases had significantly higher percentage of serological manifestation presence than clinically diagnosed APS cases. Though there is no statistically significance, Sapporo confirmed APS cases had advanced odds of undergoing vascular thrombosis (OR = 1.61, 95%CI) and DVT/PE (OR = 1.53, 95%CI) and lesser odds of undergoing recurrent DVT/PE (OR = 0.67, 95%CI) and pregnancy morbidity (OR = 0.63, 95%CI) than the clinically diagnosed APS cases. Over 70% of the study population with diagnosed APS did not accomplish the revised Sapporo criteria due to negative laboratory manifestations, which reflects heterogeneous but not degreed disease severity profiles. [ABSTRACT FROM AUTHOR]

• Despite the SoC, women with aPL still experience pregnancy complications. • The Global AntiphosPholipid Syndrome Score is a risk stratification tool. • GAPSS might be a valuable tool for stratifying patients that will likely respond to SoC. The current treatment to prevent pregnancy morbidity (PM) associated with antiphospholipid antibodies (aPL) is based on the use of low dose aspirin and low molecular weight heparin (henceforth defined as standard of care (SoC) treatment). Despite the SoC, up to 30% of women with aPL continue to have pregnancy complications. The global antiphospholipid syndrome (APS) score (GAPSS) is a tool to quantify the risk for the aPL-related clinical manifestations. In this study, we investigated the individual clinical response to SoC in women with aPL after stratifying them according to their GAPSS. One-hundred-fourty-three women (352 pregnancies) with aPL ever pregnant treated with SoC therapy were included. The patients GAPSS was then grouped according to the patients' GAPSS into low risk (< 6), medium risk (6–11), and high risk (≥12). The live birth rate was 70.5% (248 out of the 352 pregnancies), 45 patients (31%) experienced at least one event of PM, defined as early or late. Patients were stratified according to GAPSS values, in order to identify a low risk group (GAPSS <6, n = 72), a medium risk group (GAPSS 6–11, n = 66) and a high risk group (GAPSS ≥12, n = 5). When considering patients who ever experienced any PM while treated with SoC, all patients in the high risk group experienced PM, while patients in the medium group had a significant higher rate of PM when compared to the low risk group [29 (43.9%) patients V.s. 11 (15.3%), respectively; p < 0.001]. When analysing the number of pregnancies in the three groups, patients in the high risk group had significantly lower live birth rates, when compared to the other groups [11 (40.7%) live births vs. 100 (62.1%) and 137 (82.5%), respectively; p < 0.05]. Furthermore, patients with medium risk group also had significantly lower live birth rates, when compared to the lower risk group (p < 0.001). GAPSS might be a valuable tool for to identify patients with a higher likelihood of response to SoC. [ABSTRACT FROM AUTHOR]

The antiphospholipid syndrome (APS) was fully recognized as a clinical entity in the early 1980s. Still, more than 30 years later, the epidemiology of APS is not well described, and furthermore, APS remains a challenge in terms of both diagnostic issues and clinical praxis involving a wide range of specialties. To date, there are no diagnostic criteria for APS. The present classification criteria rely on a combination of clinical manifestations and persistently positive tests for antiphospholipid antibodies (aPL). Clinical symptoms comprise vascular thrombosis, which can affect any vascular bed, including venous, microvascular and arterial vessels, and a set of pregnancy morbidities including early and late miscarriages, foetal death and preeclampsia. APS is more frequent among patients with other autoimmune diseases, and it is especially common in systemic lupus erythematosus (SLE). Importantly, APS symptoms can present in almost any medical specialty, but general knowledge and most previous clinical studies have essentially been confined to haematology, rheumatology and obstetrics/gynaecology. However, recent data demonstrate a relatively high prevalence of aPL also in patients from the general population who suffer from vascular occlusions or pregnancy complications. It is important that these patients are recognized by the general health care since APS is a treatable condition. This review aims to summarize the present knowledge on the history, pathogenesis, clinical manifestations and treatment of APS in order to urge a wide range of clinicians to consider comprehensive assessment of all patients where the diagnosis APS may be conceivable. [ABSTRACT FROM AUTHOR]

Anti-β2GPI-Domain 1 (β2GPI-D1) antibodies are considered to be a pathogenic subset of anti-β2GPI antibodies and have been strongly associated with thrombosis and pregnancy morbidity in patients with antiphospholipid syndrome (APS). We evaluated the clinical utility of anti-β2GPI-D1 IgG antibodies for stratifying the risk of thrombosis and/or pregnancy morbidity (PM) in a cohort of Chinese patients with APS and also assessed its correlation with the Global Anti-Phospholipid Syndrome Score (GAPSS). Sera and plasma from 192 consecutive APS patients, 17 aPL carriers, 193 patients with other systemic autoimmune diseases, and 120 healthy controls were collected and the presence of aCL IgG/IgM, anti-β2GPI IgG/IgM and anti-β2GPI-D1 IgG antibodies were assessed by chemiluminescence assays (CIA). Detection of LAC was performed according to international guidelines with the use of screening, mixing and confirmation tests. Anti-phosphatidylserine-prothrombin (aPS/PT) IgG and IgM antibodies were detected by commercial ELISA kits. Anti-β2GPI-D1 IgG antibodies showed high specificity (97.12%) and moderate sensitivity (64.32%) for the diagnosis of APS. Anti-β2GPI-D1 antibodies levels were significantly higher in patients with triple aPL positivity than in those with double (P < 0.001) and single positive aPL (P < 0.001) and correlated well with the GAPSS (rho = 0.60, P < 0.001). Anti-β2GPI-D1 antibodies presented with a higher prevalence and higher titers in patients with late pregnancy morbidity (≥10 weeks) and thrombotic APS compared to those with early pregnancy (<10 weeks) morbidity. Higher anti-β2GP1-D1 antibodies titers effectively distinguished APS from other autoimmune diseases. This study suggests a predictive role of anti-β2GPI-D1 IgG antibodies as a strong risk factor for both thrombotic and obstetric APS (OAPS), especially for stratification comparing early PM with late PM and thrombosis. • Anti-β2GPI-D1 IgG antibodies showed high specificity and moderate sensitivity for the diagnosis of APS. • Anti-β2GPI-D1 antibody levels were highest in patients with triple aPL positivity and correlated well with the GAPSS. • Anti-β2GPI-D1 IgG antibodies as an important factor for stratification comparing early PM with late PM and thrombosis. • Higher anti-β2GP1-D1 antibody titers effectively distinguished APS from other autoimmune diseases. [ABSTRACT FROM AUTHOR]

Extra-criteria manifestations such as thrombocytopenia and livedo are described associated with antiphospholipid syndrome (APS) but are not included in the current classification criteria. Their clinical expression might be important, as they may be associated with a high-risk profile of antiphospholipid antibodies (aPL) and thrombosis. We evaluated the association between the presence of extra-criteria manifestations in primary obstetric-APS (POAPS) and aPL profiles. We also evaluated whether the presence of extra-criteria manifestations in POAPS patients increases the risk of developing thrombosis during the follow-up period (median follow-up 5 years; range 3–9 years). We selected 79 women who were included in our study only if they were first diagnosed with POAPS (with no history of previous thrombosis) and reevaluated for the presence of thrombosis after the follow-up period. We evaluated the association between the aPL profile and extra-criteria manifestations. We also evaluated the relationship of thrombosis during the follow-up period with extra-criteria manifestations and other risk factors. Patients with three or more extra-criteria manifestations presented high rates of triple positivity for the aPL profile (75%) (p < 0.001). We also found a relationship between the presence of extra-criteria manifestations and the presence of high titers of aPL: 91.7% of patients with three or more extra-criteria manifestations had high titers of aPL (p < 0.01). We further evaluated the group of POAPS patients according to thrombotic events during the follow-up. Among these patients, 6 (7.6%) presented thrombosis. Notably, 100% of patients with a thrombotic event during the follow-up had more than three extra-criteria manifestations. POAPS patients with extra-criteria manifestations might have a high-risk aPL profile and a major risk of developing thrombosis. [ABSTRACT FROM AUTHOR]

The objective was to develop evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. Based on evidence from a systematic literature review and expert opinion, overarching principles and recommendations were formulated and voted. High-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS. Risk modification includes screening for and management of cardiovascular and venous thrombosis risk factors, patient education about treatment adherence, and lifestyle counselling. Low-dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with systemic lupus erythematosus without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin K antagonists (VKA) with a target international normalised ratio (INR) of 2-3. In patients with APS with first arterial thrombosis, treatment with VKA with INR 2-3 or INR 3-4 is recommended, considering the individual's bleeding/thrombosis risk. Rivaroxaban should not be used in patients with APS with triple aPL positivity. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3-4 or switch to low molecular weight heparin may be considered. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increase of heparin to therapeutic dose, addition of hydroxychloroquine or addition of low-dose prednisolone in the first trimester may be considered. These recommendations aim to guide treatment in adults with APS. High-quality evidence is limited, indicating a need for more research. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a rare autoimmune disease of unknown etiology that represents a leading cause of acquired thromboembolism and recurrent miscarriage. It is characterized by the persistent elevated presence of pathogenic antiphospholipid auto-antibodies directed against cardiolipin, ß2-glycoprotein-I, and/or a positive lupus anticoagulant test. As with many autoimmune disorders, the pathogenesis of APS is believed to be the result of a complex interaction between environmental triggers and genetic predisposition. Although more common in adults, APS occasionally manifests in the neonatal period and throughout childhood. Adut-onset APS classification criteria are poorly validated to the pediatric population (in which pregnancy related complications are seldom seen) and as a result, assessment of the prevalence of the disease in childhood is difficult. Thromboembolic events seen in children include deep venous thrombosis in addition to stroke and pulmonary embolism, which can lead to significant long-term disability. The disease can be classified as either primary (when occurring in isolation) or secondary, in which the disease is diagnosed in the context of another underlying disease, most commonly systemic lupus erythematosus. A variety of laboratory and clinical difference are seen between pediatric and adult-onset APS. The marked female predominance seen in adult-onset disease is less evident in childhood where the gender split is more evenly spread. In addition, children with APS are at a higher risk of recurrent thromboembolism than adults. The treatment of childhood-onset APS is challenging due to a lack of large-scale prospective studies in the pediatric population. Therapeutic options are often based upon treatment guidelines that have been based upon literature from the adult-onset form of the disease. In the majority of cases, treatment is focused on the prevention of further thrombosis through treatment with long-term anti-coagulation therapy. The evidence for the use of antiplatelet agents (such as aspirin) and hydroxychloroquine is inconclusive. It is important to remember that anti-coagulation can have significant lifestyle implications for the child with APS and it is essential to consider potential implications relating to school and recreational activities, with contact sports often discouraged due to the increased risk of bleeding.

Introduction: Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia associated with the presence of persistent antiphospholipid antibodies (aPL). Owing to recent studies, not only APS patients but also incidentally-identified, asymptomatic aPL carriers are able to be stratified in terms of the risk of future thrombotic events, according to the variety and the titer of positive aPL tests and to the non-thrombotic, aPL-associated clinical manifestations. Areas covered: Here, we critically review (1) criteria manifestations of APS, (2) non-criteria manifestations of APS, (3) risk assessment in patients with APS and in aPL carriers, and (4) the potential role of primary thrombosis prophylaxis in aPL carriers. In addition, we discuss what we are currently able to do and what we need to do in the future for primary prophylaxis against a first thrombotic event. Expert commentary: We suggest a comprehensive algorithm to stratify thrombotic risk in aPL carriers, including criteria aPL, non-criteria aPL, their scoring systems, and non-criteria manifestations. However, further studies, particularly prospective randomized controlled trials, are highly warranted to establish an effective and tolerable treatment regimen for high risk aPL carriers. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibodies (aPL) cause vascular thrombosis (VT) and/or pregnancy morbidity (PM). Differential mechanisms however, underlying the pathogenesis of these different manifestations of antiphospholipid syndrome (APS) are not fully understood. Therefore, we compared the effects of aPL from patients with thrombotic or obstetric APS on monocytes to identify different molecular pathways involved in the pathogenesis of APS subtypes. VT or PM IgG induced similar numbers of differentially expressed (DE) genes in monocytes. However, gene ontology (GO) analysis of DE genes revealed disease-specific genome signatures. Compared to PM, VT-IgG showed specific up regulation of genes associated with cell response to stress, regulation of MAPK signalling pathway and cell communication. In contrast, PM-IgG regulated genes involved in cell adhesion, extracellular matrix and embryonic and skeletal development. A novel gene expression analysis based on differential variability (DV) was also applied. This analysis identified similar GO categories compared to DE analysis but also uncovered novel pathways modulated solely by PM or VT-IgG. Gene expression analysis distinguished a differential effect of VT or PM-IgG upon monocytes supporting the hypothesis that they trigger distinctive physiological mechanisms. This finding contributes to our understanding of the pathology of APS and may lead to the development of different targeted therapies for VT or PM APS. [ABSTRACT FROM AUTHOR]

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 research ELISA assay, respectively (QUANTA Flash ® β2GPI Domain 1 IgG and QUANTA Lite ® β2GPI D4/5 IgG, Inova Diagnostics). Positivity for anti-D1 antibodies, but not anti-D4/5 antibodies, was differently distributed across the 4 subgroups of patients (p < 0.0001) and significantly correlated with thrombosis (χ2 = 17.28, p < 0.0001) and PM (χ2 = 4.28, p = 0.039). Patients with triple positivity for anti-phospholipid antibodies displayed higher anti-D1 titres and lower anti-D4/5 titres compared to women with one or two positive tests (p < 0.0001 and p = 0.005, respectively). Reactivity against D1 was identified as a predictor for PM (OR 2.4, 95% confidence interval [CI] 1.2–5.0, p = 0.017); in particular, anti-D1 antibodies were predictive of late PM, conveying an odds ratio of 7.3 (95% CI 2.1–25.5, p = 0.022). Positivity for anti-D1 antibodies was not associated with early pregnancy loss. Anti-D4/5 antibodies were not associated with clinical APS manifestations. As a whole, our data suggest that anti-D1 antibodies are significantly associated not only with thrombosis, but also with late PM, while positive anti-D4/5 antibodies are not predictive of thrombosis or PM. [ABSTRACT FROM AUTHOR]

Objective IgG and IgM antibodies directed at β2-glycoprotein I are included in the classification criteria for the antiphospholipid syndrome (APS) while the IgA antibodies against β2-glycoprotein I (IgA aβ2GPI) are not. Conflicting data about the significance of IgA aβ2GPI and APS manifestation can be found and more studies are necessary in order to define the diagnostic value of IgA aβ2GPI. In the present article, we investigated the possible role of IgA aβ2GPI as marker of APS. Methods A cohort of 314 patients with APS and systemic autoimmune disease was investigated for the presence of IgA aβ2GPI and its association with clinical manifestation of APS. Results Eighty-nine patients presented IgA aβ2GPI, 68 cases associated with others antiphospholipid antibodies (aPL) and in 21 cases being the only aPL present. In primary APS IgA aβ2GPI are highly coincidental with other aPL (92,2%) while most of the isolated IgA aβ2GPI were present in the SLE group (16/21). No association between IgA aβ2GPI and APS manifestations: thrombosis and pregnancy morbidity was found, while a positive association between IgA aβ2GPI and the presence of anti-nDNA, anti-RNP, anti-Sm, anti-SSA, anti-SSB antibodies was encountered. Conclusion Our study does not show association between IgA aβ2GPI and APS manifestations and does not support the inclusion of IgA aβ2GPI as a classification criteria for APS. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibody syndrome (APS) is an autoimmune acquired thrombophilia characterized by recurrent thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). APS can be primary, if it occurs in the absence of any underlying disease, or secondary, if it is associated with another autoimmune disorder, most commonly systemic lupus erythematosus. The exact pathogenetic mechanism of APS is unknown, but different, not mutually exclusive, models have been proposed to explain how anti-PL autoantibodies might lead to thrombosis and pregnancy morbidity. Diagnosis of APS requires that a patient has both a clinical manifestation (arterial or venous thrombosis and/or pregnancy morbidity) and persistently positive aPL, but the clinical spectrum of the disease encompasses additional manifestations which may affect every organ and cannot be explained exclusively by a prothrombotic state. Treatment for aPL-positive patients is based on the patient's clinical status, presence of an underlying autoimmune disease, and history of thrombotic events. In case of aPL positivity without previous thrombotic events, the treatment is mainly focused on reduction of additional vascular risk factors, while treatment of patients with definite APS is based on long-term anticoagulation. Pregnancy complications are usually managed with low-dose aspirin in association with low molecular weight heparin. Refractory forms of APS could benefit from adding hydroxychloroquine and/or intravenous immunoglobulin to anticoagulation therapy. Promising novel treatments include anti-B cell monoclonal antibodies, new-generation anticoagulants, and complement cascade inhibitors. The objective of this review paper is to summarize the recent literature on APS from pathogenesis to current therapeutic options. [ABSTRACT FROM AUTHOR]

Background: Antiphospholipid syndrome (APS) is an autoimmune disorder characterised by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPLs) based on the Sydney criteria. We aimed to explore the clinico-laboratory features and treatment strategies of APS patients retrospectively. Methodology: The medical records of APS patients registered under Hospital Universiti Sains Malaysia (Kelantan state) between 2000 and 2015 were reviewed. Results: A total of 17 APS subjects (age 40.7 ± 12.8 years) including 11 primary (64.7%) and six secondary APS (35.3%) patients were identified. The follow-up period was 9.5 ± 6.7 years with male:female ratio of 1.0:4.7. Pregnancy morbidity was the most common clinical manifestation (11/14; 78.6%) followed by recurrent venous thrombosis (10/17; 58.8%). For other clinical features, menorrhagia was the most frequently observed manifestation (4/14; 28.6%) followed by aPLs-associated thrombocytopenia (4/17; 23.5%) and ovarian cyst (3/14; 21.4%). LA and aCL were positive in 94.1% (16/17) and 81.8% (9/11) of the patients, respectively. APTT value (76.7 ± 17.0 sec) was significantly high (p < 0.05). Low intensity warfarin alone was successful to maintain target INR (2.0 - 3.0) and prevent recurrence of thrombosis. Conclusion: The tendency of pregnancy morbidity in this cohort of Malaysian Kelantanese APS patients was high compared to other previously reported APS cohorts. Low intensity warfarin was successful in preventing recurrence of thrombosis, however, APS women receiving long-term anticoagulants should be monitored for possible occurrence of menorrhagia and ovarian cysts. [ABSTRACT FROM AUTHOR]

Background: While essential for the classification of antiphospholipid syndrome (APS), anticardiolipin (aCL) assays lack specificity and anti-β2glycoproteinI (anti-β2GPI) assays lack sensitivity in this regard. Our aim was to perform a comparative analysis of the APhL ELISA assay (IgG/IgM) and criteria antiphospholipid (aPL) immunoassays in identifying APS-related clinical manifestations in a large group of patients with systemic lupus erythematosus (SLE). Methods: Serum samples from 1178 patients from the Hopkins (n=543), LUMINA (n=588) and Jamaican SLE cohorts (n=47) were examined for IgG/IgM positivity in aCL (in-house), anti-β2GPI (two commercial kits) and APhL (Louisville APL) ELISA assays. Correlation of assay positivity with clinical manifestations and sensitivity, specificity, positive and negative predictive values and likelihood ratios were evaluated. A case series analysis was also performed in patients for whom there was isolated positivity in the specific aPL assays. Results: The prevalence of aCL positivity was 34.9%, anti-β2GPI kit A was 22.6%, APhL was 11.5% and anti-β2GPI kit B was 7.6% in the study population. Anti-β2GPI kit B, aCL and APhL assays were correlated with venous thrombosis, while only APhL was significantly correlated with arterial thrombosis and consistently correlated with pregnancy-related morbidity. No significant correlations were noted for anti-β2GPI kit A. Sensitivity was greatest for aCL assays followed by anti-β2GPI kit A, APhL and anti-β2GPI kit B, while specificity was greatest and equal for anti-β2GPI kit B and APhL assays. Conclusions: Overall, APhL antibodies, especially IgG, represent a promising biomarker for the classification of APS patients in the context of autoimmunity and in risk assessment with regards to pregnancy morbidity and thrombotic manifestations. [ABSTRACT FROM AUTHOR]

Problem Women with antiphospholipid antibodies ( aPLs) present a risk of pregnancy morbidity ( PM), vascular thrombosis ( VT), or both ( PM/ VT). aPLs affect trophoblast function, and the aim of this study was to determine the modulation of this aPL-induced damage by different drugs. Method of study IgG was obtained from women with PM and PM/ VT positive to aPLs. Binding of IgG to trophoblastic cells, proliferation, mitochondrial membrane integrity, and trophoblast invasion were assessed. The effect of enoxaparin, aspirin, and aspirin-triggered lipoxin ( ATL) were evaluated as well as signal transducer and activator of transcription 3 ( STAT3) phosphorylation. Results IgG from women with aPLs strongly binds to trophoblastic cells. Integrity of mitochondrial membrane was reduced, and proliferation was increased by IgG- PM/ VT. Both IgG- PM and IgG- PM/ VT decreased trophoblast invasion, which was restored by enoxaparin, aspirin, and ATL. IgG- PM triggered reduction in STAT3 phosphorylation. Conclusion Some drugs used to prevent aPL-induced PM modulated the alteration of trophoblast function. [ABSTRACT FROM AUTHOR]

El síndrome antifosfolípido es un trastorno multisistémico adquirido y una importante causa de trombosis venosas o arteriales, así como también de morbilidad en el embarazo. Puede ser primario o secundario, este último sobre todo en pacientes con lupus eritematoso sistémico, infecciones y consumo de algunas drogas. Se exponen determinados elementos sobre sus manifestaciones clínicas y los criterios de clasificación actualizados para el diagnóstico. El tratamiento se basa en medidas de profilaxis antitrombóticas y control de los factores de riesgo asociados; pero aún muchos aspectos clínicos y de laboratorio concernientes a esta hipercoagulabilidad por la presencia de anticuerpos contra los fosfolípidos, se hallan sujetos a discusión e investigación.The antiphospholipid syndrome is an acquired multisystemic disorder and an important cause of venous or arterial thrombosis, as well as of morbidity in pregnancy. It can be primary or secondary, the last one mainly in patients with systemic lupus erythematosus, infections and consumption of some drugs. Certain elements on its clinical manifestations and the updated classification criteria for the diagnosis are exposed. The treatment is based on antithrombotic prevention measures and control of the associated risk factors; but many clinical and laboratory aspects concerning this hypercoagulability due to the presence of antibodies against phospholipids, are still under discussion and research.