Antiphospholipid Syndrome Classification Research Articles

Rethinking antiphospholipid syndrome to guide future management and research.

Antiphospholipid syndrome (APS) consists of thrombotic, non-thrombotic and obstetric clinical manifestations developing in individuals with persistent antiphospholipid antibodies (aPL). Although researchers have made progress in characterizing different clinical phenotypes of aPL-positive people, the current approach to clinical management is still mostly based on a 'one size fits all' strategy, which is derived from the results of a limited number of prospective, controlled studies. With the 2023 publication of the ACR-EULAR APS classification criteria, it is now possible to rethink APS, to lay the groundwork for subphenotyping through novel pathophysiology-informed approaches, and to set a future APS research agenda guided by unmet needs in clinical management.

Assessment and comparison of the 2023 ACR/EULAR APS criteria with the revised Sapporo criteria.

To analyze antiphospholipid antibody (aPL)-positive patients using the 2023 American College of Rheumatology/The European Alliance of Associations for Rheumatology (ACR/EULAR) antiphospholipid syndrome (APS) classification criteria and compare the revised Sapporo criteria and the 2023 ACR/EULAR criteria and evaluate whether the 2023 ACR/EULAR criteria provide added value over the revised Sapporo criteria. In this descriptive study, 94 aPL-positive patients (with or without APS diagnosis) were identified from two hospital-based registries (Gazi and Hacettepe University). Patients were classified into four groups to compare both criteria sets. These four groups are as follows: (1) patients classified with only the revised Sapporo criteria; (2) patients classified with only the 2023 ACR/EULAR APS criteria; (3) patients classified with both two criteria sets; and (4) patients classified with neither two criteria set. Of the 94 patients, 11 were classified with only the revised Sapporo criteria; one with only the 2023 ACR/EULAR APS criteria; 52 with both criteria sets; and 30 with neither set of criteria. For these 94 patients, the operating characteristics of the 2023 ACR/EULAR APS criteria, using the revised Sapporo criteria as the gold standard, the 2023 ACR/EULAR APS entry criteria demonstrated 100% sensitivity, and the 2023 ACR/EULAR APS classification criteria demonstrated 98% specificity and 82.5% sensitivity. The study emphasizes the importance of recognizing differences in clinical manifestations, such as early pregnancy loss without severe preeclampsia (PEC) and/or severe placental insufficiency (PI) and calls for a nuanced discussion on anticardiolipin (aCL) and anti-beta 2-glycoprotein-I (anti-β2GPI) immunoglobulin G (IgG) cutoff values.

Setting the Bar Differently: How to Navigate Old And New Sets of Criteria for the Classification of Antiphospholipid Syndrome.

Setting the Bar Differently: How to Navigate Old And New Sets of Criteria for the Classification of Antiphospholipid Syndrome.

Diagnosis and Management of Catastrophic Antiphospholipid Syndrome and the Potential Impact of the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria.

Catastrophic antiphospholipid syndrome (CAPS) is a rare and life-threatening condition characterized by the persistence of antiphospholipid antibodies and occurrence of multiple vascular occlusive events. CAPS currently remains a diagnostic challenge and requires urgent treatment. The diagnosis of CAPS is made difficult by classification criteria used as diagnostic criteria in clinical practice, knowledge derived from retrospective data and case reports, confounding clinical and biological features, and its rapid onset and mortality. The absence of prospective studies of CAPS limits the strength of evidence for guideline treatment protocols. This comprehensive review summarizes the current understanding of the disease, and discusses how the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria impact the definition and therapeutic management of CAPS, which is considered the most severe form of APS. The correct integration of 2023 ACR/EULAR APS classification criteria is poised to facilitate CAPS diagnosis, particularly in critical situations, offering a promising avenue for improved outcomes.

Performance validation of the 2023 American College of Rheumatology/European League Against Rheumatism antiphospholipid syndrome classification criteria in an antiphospholipid syndrome cohort

BackgroundThe 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) antiphospholipid syndrome (APS) classification criteria were developed with higher specificity but lower sensitivity compared with the 2006 Sydney revised classification criteria. ObjectivesTo validate the performance of the 2023 ACR/EULAR APS classification criteria in a large Chinese APS cohort. MethodsThis was a single-center cohort study. Inclusion criteria aligned with the entry criteria of 2023 criteria. APS classification by “expert consensus panel” served as the gold standard. Sensitivity and specificity were compared between the 2023 and 2006 criteria. ResultsA total of 526 patients with a mean age of 38.55 ± 12.67 years were enrolled, of whom 366 (69.58%) were female and 182 (34.60%) had systemic lupus erythematosus (SLE). Among them, 407 (77.38%) patients were classified as APS by experts. The 2023 criteria demonstrated higher overall specificity than the 2006 criteria (0.983 vs 0.950), while sensitivity was relatively lower (0.818 vs 0.853). The sensitivity of the 2023 criteria improved for patients with SLE (0.860 vs 0.825), microvascular manifestations (0.867 vs 0.786), cardiac valve disease (0.903 vs 0.774), and thrombocytopenia (0.811 vs 0.790). Reduced sensitivity of the 2023 criteria was linked to the omission of certain microvascular manifestations, a stricter definition of pregnancy morbidity, and the exclusion of isolated thrombocytopenia and isolated IgM isotype antiphospholipid antibodies from meeting clinical and laboratory criteria, respectively. ConclusionThe 2023 criteria offer higher overall specificity and improved sensitivity in specific patient subsets, such as those with SLE, microvascular manifestations, cardiac valve disease, and thrombocytopenia when compared with the 2006 criteria.

Antiphospholipid Syndrome: To Classify or Not to Classify?

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder resulting in thrombosis, microvascular disease, morbidity in pregnancy, and/or non-thrombotic manifestations. The recently introduced 2023 American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) APS classification criteria, with significantly higher specificity compared to the revised Sapporo criteria, now reflect the current thinking about APS and provide a new foundation for future APS research. The purpose of this short commentary is to discuss the appropriate circumstances under which the 2023 ACR/EULAR classification criteria could be used and to demonstrate how the new criteria can be applied to simple case scenarios.

Discouraging Non-ELISA antiphospholipid antibody assays in antiphospholipid syndrome classification may hinder clinical research

Discouraging Non-ELISA antiphospholipid antibody assays in antiphospholipid syndrome classification may hinder clinical research

Quantification of Antiphospholipid Antibodies: The Importance of Using an Appropriate Methodology for Each Clinical Profile.

The presence of antiphospholipid antibodies (aPLs) is associated with antiphospholipid syndrome (APS), characterized by thrombosis and obstetric morbidity. aPLs included in APS classification criteria are lupus anticoagulant, anti-cardiolipin and anti-beta-2-glycoprotein-I of IgG or IgM isotypes. Enzyme-linked immunosorbent assay is the most used diagnostic technique to determine aPLs. Recently, new automated technologies mainly based in antigen-coated beads have been developed. The aim is to compare a fluorescence enzyme immunoassay (M1) and an antigen-coated bead assay (M2) in obstetric and thrombotic APS patients. All samples from the first 1020 patients received in the Immune Service Laboratory (Hospital 12 de Octubre) during the recruitment period, without exclusions, were analysed for aPLs. The weighted kappa for both methods in all the patients was 0.39 (0.30-0.47). Agreement increased to 0.56 (0.38-0.73) in patients with autoimmune disease. Sensitivity and specificity obtained for M1 were 17.1% and 89.3%, respectively, and 12.7% and 91.4% for M2. The sensibility and specificity of IgG isotypes were higher than the IgM ones. Regarding obstetric patients, M1 obtained significant diagnostic performance and had more sensitivity 23.75 (14.95-34.58) compared to M2 12.50 (6.16-21.79). In conclusion, clinical suspicion-based method selection for aPLs should be considered. To identify obstetric APS patients, solid phase methods remain more preferable.

Antiphospholipid Antibodies and Vascular Thrombosis in Patients with Severe Forms of COVID-19.

Antiphospholipid antibodies (aPLA) are a laboratory criterion for the classification of antiphospholipid syndrome (APS) and are known to cause clinical symptoms such as vascular thrombosis or obstetric complications. It is suggested that aPLA may be associated with thromboembolism in severe COVID-19 cases. Therefore, we aimed to combine clinical data with laboratory findings of aPLA at four time points (admission, worsening, discharge, and 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. In 111 patients with COVID-19 pneumonia, current and past history of thrombosis and pregnancy complications were recorded. Nine types of aPLA were determined at four time points: anticardiolipin (aCL), anti-β2-glycoprotein I (anti- β2GPI), and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG, or IgA isotypes. During hospitalization, seven patients died, three of them due to pulmonary artery thromboembolism (none were aPLA positive). Only one of the five who developed pulmonary artery thrombosis was aPLA positive. Out of 9/101 patients with a history of thrombosis, five had arterial thrombosis and none were aPLA positive at admission and follow-up; four had venous thrombosis, and one was aPLA positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPLA positive at discharge only, compared to 26.1% without a history of thrombosis (p = 0.041). Patients with severe forms of COVID-19 and positive aPLA should receive the same dose and anticoagulant medication regimen as those with negative aPLA because those antibodies are mostly transiently positive and not linked to thrombosis and fatal outcomes.

Proteomic Profiling of Different Antiphospholipid Antibody-Positive Phenotypes: Results from Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Registry

Background. Antiphospholipid syndrome (APS) is an autoimmune disease with thrombotic and obstetric complications arising via a model of immunothrombosis. Patients may present with a spectrum of phenotypes, including thrombotic (tAPS), obstetric (oAPS), or catastrophic/microvascular APS (C/MAPS), while others may have antiphospholipid antibodies (aPL) without disease manifestations. The mechanisms underlying the development of these diverse phenotypes remain uncertain. Proteomic profiling was used in other thrombotic and microvascular disorders to highlight potential mechanisms of disease pathogenesis and may have a role in understanding the pathophysiology of APS. We performed multiplex plasma proteomic profiling in aPL-positive patients with different clinical phenotypes to gain a greater understanding of potential immunothrombotic mechanisms in the pathogenesis of APS. Methods. We utilized samples from APS ACTION Registry. The inclusion criteria were positive aPL per Updated Sapporo Classification Criteria tested within one year prior to the enrollment. Multiplex proteomic profiling measuring approximately 7,000 unique proteins (SomaLogic; Boulder, CO, USA) was performed on 40 primary aPL-positive patient plasma samples (10 each of tAPS with/without oAPS, oAPS only, C/MAPS, and positive aPL without APS classification), and 10 of healthy controls. Differentially abundant proteins among all phenotypic groups and in pairwise comparisons were determined by applying ANOVA and t-tests to log-normalized data, respectively, with p-values <0.05 considered statistically significant (Qlucore Omics Explorer, Lund, Sweden). Tests were adjusted for false discovery (q<0.1) to minimize the likelihood of false positives. Pathway enrichment analysis was performed using Metascape (https://metascape.org) and Ingenuity IPA (Qiagen, Venlo, Netherlands) platforms. Results. The median age of patients was 48 years; 30% were men, 70% had triple aPL-positivity, and no one had a concurrent diagnosis of lupus. A set of concordant and differentially abundant proteins clustered patients with 4 APS clinical phenotypes and controls (Figure A) with a high statistical significance (p<0.0007) and a high false discovery confidence (q<0.05). Proteins in the identified set belonged to several highly enriched pathways such as neutrophil degranulation (p<10 -10), humoral immune response (p<10 -9), coagulation (p<10 -6), and alternative complement (p<10 -5) [data not shown]. Pathway enrichment analysis of protein sets identified in pairwise comparisons of APS phenotypes (aPL vs C/MAPS, aPL vs tAPS, tAPS vs C/MAPS) revealed involvement of several common pathways associated with inflammation, collagen and fibroblast signaling, cellular and cytoskeletal activation, humoral immune response, myeloid and effector cell differentiation and recruitment, and immunothrombosis such as Pathogen-Induced Cytokine Storm, Neutrophil Extracellular Trap (NET), and collagen-induced platelet-activating GP6 signaling (Figure B). For several pathways, the measure of activation related to increased or predicted to be increased proteins annotated within a particular pathway positively correlated with the clinical “distance” between APS subtypes, from the most clinically related C/MAPS vs tAPS to the most distant aPL vs C/MAPS suggesting an “evolution” from one phenotype to a more severe in terms of activation of specific pathways. Specifically notable is the higher activation of the NET signaling pathway in the aPL than in C/MAPS phenotype suggesting that the presence of aPL antibodies activates this immunothrombotic pathway. Conclusions. Plasma proteome of APS subtypes is characterized by alteration in several cellular processes, particularly receptor signaling, signal transduction, regulation of cellular differentiation, neutrophil, complement, coagulation and cytokine activation notable in all individuals with aPL-positivity. Pathways activated in the non-thrombotic (aPL) phenotype and escalating activation of several pathways from non-thrombotic to the most thrombotic (C/MAPS) phenotype provide important data for the understanding of APS pathogenesis and informing the model of APS-related immunothrombosis.

Do Patients with Antiphospholipid Syndrome Have More Significant Venous Thromboembolic Clot Burden?: A Single-Center Retrospective Analysis

Background: Antiphospholipid syndrome (APS) is a prothrombotic condition defined by arterial or venous thrombotic events and/or obstetrical morbidity in the presence of persistently positive antiphospholipid antibodies (aPL). Venous thromboembolic disease (VTE), comprised mostly of deep vein thrombosis (DVT) and pulmonary embolism (PE), is the initial presenting clinical manifestation in approximately 35% of APS diagnoses. VTE is a heterogenous disease and can present with varying degrees of clot burden. Lower extremity DVT can present with thrombus in the iliofemoral, femoropopliteal, and/or distal calf veins; pulmonary embolism can present with thrombus in the main pulmonary arteries, lobar branches, segmental, and/or subsegmental branches. In both DVT and PE, more proximal clot burden portends higher morbidity and mortality. While VTE is a commonly encountered clinical presentation, the decision regarding whom to test for APS is often challenging. Current guidelines recommend that clinicians consider testing for APS in patients with unexplained venous or arterial thrombotic events, especially young patients, or when a patient has one or more specific adverse outcomes related to pregnancy. To date, no data exist to suggest that patients with APS are more likely to present with more extensive venous thromboembolic clot burden as compared to patients without APS. Purpose: To assess clot burden in patients with a co-diagnosis of VTE and APS in comparison to patients with VTE without APS to determine if clot burden should be considered when deciding whom to test for APS. Methods: This retrospective cohort study included adult patients with a history of VTE who had also been tested for APS within a multihospital academic healthcare system from December 1, 2019 through January 31, 2022. All patients in the study had a history of VTE and were considered to be positive for APS if they had persistently positive aPL and/or lupus anticoagulant in accordance with the revised Sapporo APS Classification Criteria. Patients were excluded if they had confounding provoking risk factors for thrombosis. Patients were stratified as APS and non-APS. Significant clot burden was defined as PE involving the main and/or lobar pulmonary arteries or DVT involving the iliofemoral veins. Assessment of clot burden was performed by review of radiology reports of the sentinel clotting event.Patients were further stratified based on age, BMI, insurance status, severity of APS (triple-positive APS versus non-triple-positive APS), and type of APS (primary versus secondary). Exploratory analysis of the patient groups was performed. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Chi square test was used to compare percentages and t-test was used to compare means. Univariate and multivariate regression models were used to analyze the predictors of significant clot burden. Results: We identified 748 patients with a history of VTE who had also been tested for APS. The study population was comprised of 53.1% females with a median age of 59 (IQR 46-69). A majority of the patients were Caucasian (85%). APS was detected in 75 (10%) patients. Significant clot burden was present in 29 (38.7%) APS patients and 269 (40.0%) non-APS patients (OR 0.95, 95% CI 0.58-1.56; P = 0.85). On univariate analysis, age (OR 1.01, 95% CI 1.00-1.02; P = 0.02) and being uninsured (OR 9.2, 95% CI 1.10-76.10; P = 0.04) were associated with more significant clot burden. No predictors for significant clot burden were found on multivariable analysis. Triple positive APS (OR 0.83, 95% CI 0.16-4.21; P = 0.82) and primary APS (OR 0.72, 95% CI 0.15-3.45; P = 0.68) were not associated with more significant clot burden. Conclusions: In this retrospective cohort of 748 patients with a history of VTE, the presence of antiphospholipid syndrome was not associated with more significant VTE clot burden as compared to non-APS patients. Based on these data, VTE clot burden may not be a reliable predictor for the presence of APS. Study limitations include selection bias, retrospective design, and lack of precise volumetric measurement of blood clots.

The 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria.

To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR. This international multidisciplinary initiative included 4 phases: 1) Phase I, criteria generation by surveys and literature review; 2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; 3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and 4) Phase IV, validation using independent adjudicators' consensus as the gold standard. The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into 6 clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and 2 laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-β2 -glycoprotein I antibodies). Patients accumulating at least 3 points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria versus the 2006 revised Sapporo classification criteria had a specificity of 99% versus 86%, and a sensitivity of 84% versus 99%. These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research.

Antiphospholipid syndrome nephropathy: Current knowledge and unanswered questions

The definition of acute and chronic antiphospholipid syndrome (APS) nephropathy was recently updated using a multiphase methodology in the context of the development of the new APS classification criteria. Currently, there is no consensus for the treatment of APS nephropathy, which mainly relies on the general recommendations for the management of APS. Based on evidence from experimental studies and a few clinical studies and case series, targeted treatments such as B-cell depletion, anti-B-cell activating factor antibody, complement inhibition, mammalian target of rapamycin inhibition, and neutrophil extracellular traps or interferon targeting may show promise for the treatment of microvascular manifestations in APS, including APS nephropathy. Validation of the new APS nephropathy definition and/or efforts for improvement in proposed terminology, along with the assessment of the safety and efficacy of potential targeted treatments in randomized controlled trials, are major future research directions. In this review, we summarize the current knowledge of APS nephropathy and discuss unanswered questions.

Complications and outcomes of pregnancy in patients with antiphospholipid antibodies during various treatment methods

Introduction. Antiphospholipid antibodies (APAs) exert multifaceted effects on the course of pregnancy by disrupting microcirculation, affecting the hemostasis, as well as damaging the endothelial membranes, leading to early reproductive loss and development of placenta-associated complications depending on the affected gestation stage. Planning and management of pregnancy in women in the absence of criteria for complete antiphospholipid syndrome (APS) currently remains unresolved issue. The absence of generally accepted treatment standards for this category of patients and inability to substantiate the diagnosis according to the APS classification criteria complicate selection of therapeutic tactics.Aim: to conduct a comparative analysis of therapy-based complications and outcomes of pregnancy in APA carriers.Materials and Methods. During the period 2019–2021 a prospective study of 150 patients who entered pregnancy with aggravated obstetric and gynecological history, serum APA level was examined. Considering the risks of developing obstetric and thrombotic complications, all patients were prescribed prophylactic doses of low molecular weight heparins (LMWHs) and low doses of acetylsalicylic acid (ASA). The patients were divided into 3 groups using a random number generator. Group 1 (n = 50), in addition to the prescribed LMWH (enoxaparin sodium 40 mg 1 time per day) and ASA (150 mg 1 time per day), also underwent plasmapheresis (PF) 4 sessions per 1 course in 6–8, 12–14 and 22–24 weeks of pregnancy; group 2 (n = 50) received courses of intravenous immunoglobulins (IVIG) at a course dose of 300 ml (15 g) simultaneously; group 3 (n = 50) received no additional therapies. Rate of pregnancy complications was comparatively assessed – development of fetal growth retardation (FGR), low birth weight fetus, gestational arterial hypertension (AH), moderate and severe preeclampsia (PE), anemia and delivery outcomes.Results. It was found that in group 3 there was a higher incidence of gestational hypertension (p2,3 < 0.0001), moderate PE (p 1,3 =0.071; p 2,3 = 0.0019), low weight fetus for gestational age (p2,3 = 0.0002) and FGR (p2,3 = 0.003). In group 1, compared with group 2, there were more often observed small weight for gestational age fetus (p1,2 = 0.018) and FGR (p1,2 = 0.024), gestational hypertension (p1,2 = 0.0008), anemia (p1,2 < 0.0001) and latent iron deficiency (p1,2 < 0.0001). Also, groups 2 and 3 vs. group 1 were more likely to have intrahepatic cholestasis during pregnancy (p1,2 = 0.013; p1,3 = 0.003).Conclusion. In the group of patients receiving complex therapy consisting of LMWHs prophylactic doses, low ASA doses and IVIG courses, the risks of developing placenta-associated complications and iron deficiency were reduced compared to other groups indicating about a higher efficiency of this therapy regimen. However, the development of intrahepatic cholestasis during pregnancy was less common in the group of patients receiving PF courses, in contrast to using IVIG courses, which can be accounted for by additional effect of efferent therapeutic methods and should be taken into account in a differentiated approach for management of patients with liver and gallbladder pathology.

Incidence of Antiphospholipid Syndrome: Is Estimation Currently Possible?

Antiphospholipid syndrome is a systemic autoimmune disorder characterized by vascular thrombosis and/or obstetric events in association with persistently elevated antiphospholipid antibodies. Antiphospholipid syndrome is typically considered a rare disease, but the true incidence is uncertain owing to the diverse antiphospholipid antibody-related clinical manifestations, inconsistent definitions of antiphospholipid antibody positivity, under-recognition of the disease, and limited population-based studies. Published estimates of the incidence of antiphospholipid syndrome range from approximately 2 to 80 per 100 000 person-years. A targeted literature review and applied methodology were performed to derive a best available estimate. Significant limitations of the published literature were observed, some of which have been previously reported. The incidence of antiphospholipid syndrome in the United States was estimated to be approximately 7.1 to 13.7 per 100 000 person-years in the general population. Although this estimate is likely more accurate than previously reported estimates, large, contemporary, population-based studies that reasonably adhere to the antiphospholipid syndrome classification criteria are needed to further refine estimates of the incidence of antiphospholipid syndrome.

Extra-criteria antiphospholipid antibodies in patients with small vessel brain lesions and clinical manifestations associated with antiphospholipid syndrome

ObjectivesNeurological manifestations compatible with small vessel brain lesions (SVBL), such as migraine, cognitive impairment, seizures, and transverse myelitis, may be related to antiphospholipid syndrome (APS) and patients could need APS therapies even though they do not fit into thrombosis or obstetric morbidity. Furthermore, extra-criteria antiphospholipid antibodies (aPL) provide an increase in sensitivity in patients with clinical manifestations related to APS but negative for IgG/IgM anticardiolipin (aCL), anti-β2 glycoprotein I (aβ2GPI), and lupus anticoagulant, which are the antibodies included in the classification criteria for APS. MethodsWe determined extra-criteria aPL in 65 SVBL patients with neurological traits and Magnetic Resonance Imaging suggestive of APS but negative for APS classification criteria, 47 of whom were prospectively followed and tested over three years. A group of 95 patients with autoimmune diseases (AD) but without clinical traits of APS was also studied. ResultsA persistent presence of extra-criteria aPL was detected in 27.7% of patients: 12.77% IgM anti- prothrombin (PT), 6.38% IgG anti-PT, 6.38% IgM anti-phosphatidylethanolamine (PE), 4.26% IgA aβ2GPI, 2.13% IgG anti-phosphatidylserine/prothrombin (PS/PT) and 2.13% IgM anti-PS/PT.There was a tendency towards a higher prevalence of these aPL in SVBL patients than in AD – especially for IgA aβ2GPI – and a lack of IgG aPS/PT positivity in the AD group. We found no SVBL patient positive for IgA aCL, IgG anti-PE, annexin V, or aβ2GPI domain I. ConclusionsExtra-criteria aPL can improve sensitivity for APS diagnosis in patients with SVBL, especially IgA aβ2GPI and IgG anti-PS/PT antibodies.

Non-Criteria Obstetric Antiphospholipid Syndrome: How Different Is from Sidney Criteria? A Single-Center Study.

This study aims to compare the demographic characteristics, clinical features, serology, and fetal-maternal outcomes between women with obstetric antiphospholipid syndrome (APS) and those with non-criteria (NC)-APS and seronegative (SN)-APS. Two-hundred and sixty-three women with APS obstetric morbidity ever pregnant were included. Of those, 66 met the APS classification criteria, 140 were NC-APS, and 57 were SN-APS. Patients with other autoimmune diseases were excluded. Adverse pregnancy outcomes (APO) included early pregnancy loss, fetal death, preeclampsia, abruptio placentae, and preterm birth. The mean age of the study group was 33.6 ± 5.3 years, and patients were followed up for 129.5 ± 81.9 months. In the NC-APS group, 31 (22.1%) did not fulfill clinical and serological criteria (Subgroup A), 49 (35%) did meet clinical but not serologic criteria (Subgroup B), and 60 (42.9%) fulfilled the serologic criteria but not the clinical ones (Subgroup C). The cardiovascular risk burden was higher in the APS group, due to a higher proportion of smoking. Patients with criteria APS received more intensive treatment than patients in the other study groups. The addition of standard of care (SoC) treatment significantly improved live birth and decreased APO in all groups. Significant clinical differences were observed between the study groups. However, when treated with SoC, fetal-maternal outcomes were similar, with a significant improvement in live births and a decrease in APO. Risk stratification in patients with obstetric morbidity associated with APS can help individualize their treatment.

Development of venous thromboembolism in an elderly man with plaque psoriasis and antiphospholipid syndrome: A case report

Antiphospholipid syndrome (APS) is a systemic autoimmune disease associated with arterial and venous thromboembolism (VTE) or recurrent fetal loss in individuals carrying antiphospholipid antibodies (aPL). We report a case of a 76-year-old man with plaque psoriasis who presented with VTE and was diagnosed with APS. APS prevalence in patients with psoriasis is currently unknown; our findings suggest that psoriasis patients with VTE may need to be screened for aPL, because the treatment strategy to prevent thrombosis recurrence is different for aPL-positive patients. A 76-year-old Japanese man with a 10-year history of plaque psoriasis presented with the right thigh swelling for 3 days on a routine follow-up. He was overweight (body mass index, 28.3), had a history of hypertension and hepatitis B virus (HBV) infection, and was a current smoker. He spent most of his time in bed since his retirement a year ago. Physical examination showed extensive right thigh swelling and tenderness with purpura (Figure 1A). Laboratory examination revealed a D-dimer level of 13.3 μg/ml (reference range, 0.0–1.0). Therefore, deep venous thrombosis (DVT) was suspected; however, he refused to undergo further testing at that time. A week later, the swelling exacerbated (Figure 1B) and extended to his right toe. He was conscious, afebrile, and reported no shortness of breath. This time, he agreed to undergo imaging studies. Contrast-enhanced computed tomography revealed DVT from the right femoral vein to the inferior vena cava and in the left popliteal vein. Additionally, pulmonary embolism was observed. Thus, the patient was diagnosed with venous thromboembolism (VTE). Serology testing for the underlying clinical conditions of VTE detected lupus anticoagulant (LA, 1.34; reference range, <1.30) and increased anticardiolipin-IgG-antibody (aCL-IgG, 52 U/ml; reference range, <10 U/ml) and anti-β2-glycoprotein I antibody (anti-β2GPI, 14.4 U/ml; reference range, <3.5 U/ml). Consequently, the patient was diagnosed with antiphospholipid syndrome (APS) and was treated with anticoagulants. Repeated testing >12 weeks apart showed LA of 1.87 and increased aCL-IgG (42 U/ml) and anti-β2GPI (20.7 U/ml), meeting the revised Sapporo APS classification criteria.1, 2 His psoriatic lesions were mild (i.e., Psoriasis Area and Severity Index, 5.6) under topical treatments at admission; however, significant recurrence of lesions requiring systemic treatment was noted 9 months after discharge (Figure 1C–D). Because of his advanced age and comorbidities including mild heart failure, HBV infection, and APS, biologics or other oral agents were avoided, and he was treated with apremilast. Four months after the initiation of apremilast, the skin lesions had considerably improved without the recurrence of VTE or other complications (Figure 1E–F). Considering the growing evidence that suggests that patients with psoriasis have an increased risk of VTE, timely recognition, and the management of risk factors for VTE are crucial to prevent thrombotic events. A 1987 study has reported a significant increase of aPL-positive patients with psoriatic arthritis.3 However, a 2008 study has shown that aPL levels were not increased among patients with plaque psoriasis as compared to healthy controls.4 Similar to the case we presented, there is a reported case of a patient with psoriasis and APS developing portal vein thrombosis.5 Additionally, there are several case reports on APS in patients with psoriasis associated with infliximab and adalimumab.6, 7 APS prevalence in patients with psoriasis diagnosed with VTE remains unknown because psoriasis8 and its common comorbidities are well-known risk factors of VTE, which may preclude physicians from screening for aPL. However, when VTE occurs, screening for aPL in these patients is essential because the treatment strategy to prevent the recurrence of thrombosis is different for aPL-positive patients.9 We would like to thank Editage (www.editage.com) for English language editing. The authors declare no conflicts of interest. The patient gave written informed consent to publish his photographs and case details. Approval of research protocol: N/A. Informed Consent: The patient provided written informed consent to publish his photographs and case details. Registry and the Registration No. of the study/trial: N/A. Animal Studies: N/A.

Characteristics of Patients With Antiphospholipid Antibody Positivity in the APS ACTION International Clinical Database and Repository.

To describe the baseline characteristics of patients with positivity for antiphospholipid antibodies (aPLs) who were enrolled in an international registry, the Antiphospholipid Syndrome (APS) Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository, overall and by clinical and laboratory subtypes. The APS ACTION registry includes adults who persistently had positivity for aPLs. We evaluated baseline sociodemographic and aPL-related (APS classification criteria and "non-criteria") characteristics of patients overall and in subgroups (aPL-positive without APS, APS overall, thrombotic APS only, obstetric APS only, and both thrombotic APS/obstetric APS). We assessed baseline characteristics of patients tested for the presence of three aPLs (lupus anticoagulant [LAC] test, anticardiolipin antibody [aCL], and anti-β2 -glycoprotein I [anti-β2 GPI]) antibodies by aPL profiles (LAC only, single, double, and triple aPL positivity). The 804 aPL-positive patients assessed in the present study had a mean age of 45 ± 13 years, were 74% female, and 68% White; additionally, 36% had other systemic autoimmune diseases. Of these 804 aPL-positive patients, 80% were classified as having APS (with 55% having thrombotic APS, 9% obstetric APS, and 15% thrombotic APS/obstetric APS). In the overall cohort, 71% had vascular thrombosis, 50% with a history of pregnancy had obstetric morbidity, and 56% had experienced at least one non-criteria manifestation. Among those with three aPLs tested (n=660), 42% were triple aPL-positive. While single-, double-, and triple aPL-positive subgroups had similar frequencies of vascular, obstetric, and non-criteria events, these events were lowest in the single aPL subgroup, which consisted of aCLs or anti-β2 GPI only. Our study demonstrates the heterogeneity of aPL-related clinical manifestations and laboratory profiles in a multicenter international cohort. Within single aPL positivity, LAC may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification.

Detection of IgA Antiphospholipid Antibodies Does not Improve Thrombotic Antiphospholipid Syndrome Classification: A two-Center Study.

BackgroundThrombotic antiphospholipid syndrome (APS) is a systemic autoimmune disease; its diagnosis requires meeting both clinical and laboratory criteria. Prevalence rates of immunoglobulin (Ig) A anticardiolipin antibodies (aCL) and IgA anti-β2 glycoprotein I antibodies (aβ2GPI) remain unknown, and the clinical value of these antibodies to APS classification remains controversial. Therefore, we aimed to examine both items in the Chinese population.MethodsUsing chemiluminescence immunoassay, antiphospholipid antibodies (aPL) were quantified in 12,582 hospital-based general population, 278 thrombotic APS patients, and 233 healthy controls.ResultsIn the general population, the positive rates of IgA aCL and IgA aβ2GPI antibodies were 2.87% and 1.99%, respectively. Furthermore, isolated IgA aPL-positivity rate was 0.72% in patients with APS, which was comparable to those in the general population (0.68%, p = 1) and in healthy controls (0.43%, p = 1). Among the IgA aPL-positive individuals in the general population, isolated IgA-positive individuals had lower serum levels of IgA antibodies (p = 0.007 for IgA aCL and p = 0.059 for IgA aβ2GPI). Regarding to APS classification, adding IgA aPL into conventional aPL assays may not improve and may even deteriorate the net reclassification index for APS; besides, no association between thrombosis and IgA aPL was observed.Conclusionsthis study assessed the prevalence of various aPL in Chinese population. IgA aPL may not enhance the classification ability of established laboratory criteria for thrombotic APS. Our data do not support the addition of IgA aPL to conventional aPL assays.