Explore the vast range of titles available.

In 2023, international rheumatology societies issued new classification criteria for antiphospholipid syndrome (APS). The criteria require scoring antiphospholipid antibody (aPL) titers as moderate or high using the traditional thresholds of 40U or 80U determined by \"standardized\" ELISA. With current popularity of non-standardized aPL assays (non-ELISA), we aimed to broaden the application of the criteria by estimating equivalent thresholds for them. Four types of aPLs (aCL/aβ2GPI-IgG/IgM) were measured using six reagents in 50 APS and 50 non-APS patients. By regression analysis of measurements between standardized ELISA and non-ELISA assays, thresholds equivalent to 10, 20, 40 and 80U were estimated for each assay. Data points below the detection limit of each assay were excluded from the regression. The diagnostic thresholds were also evaluated using \"specificity-based\" method described by the International Society on Thrombosis and Haemostasis (ISTH). This approach allegedly estimates diagnostic thresholds that attain predefined specificities of 0.975 and 0.995 in distinguishing APS from non-APS cases, respectively corresponding to moderate and high titers. The between-assay concordance of diagnostic classification using the estimated thresholds was calculated as kappa coefficient (κ). Using major-axis regression, thresholds equivalent to the traditional units (10 - 80U) were estimated for non-ELISA assays, which led to harmonized semi-quantitative classification with high κ values. Conversely, the specificity-based method yielded thresholds that dissociated from the traditional ones, particularly for IgG-isotype assays, resulting in lower κ values than regression-based method (P = 0.0039 - 0.0098). The regression-based conversion of diagnostic thresholds is practical in harmonizing diagnostic classification across major aPL assays. The specificity-based method may need adjusted predefined-specificities to estimate thresholds that are equivalent to the traditional thresholds.

The 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) have modified the laboratory domain. However, enzyme-linked immunosorbent assay (ELISA) remains the sole specified method for antiphospholipid antibody detection. This study aims to establish moderate and high levels of anticardiolipin(aCL) and anti-β2-glycoprotein I antibodies (anti-β2GPI) using chemiluminescence assay (CIA) and to investigate the diagnostic efficiency and risk stratification capabilities of CIA in comparison to ELISA. We conducted a comprehensive analysis involving 166 APS patients, 194 disease controls, and 120 healthy controls. Our assessment entailed the utilization of both ELISA and CIA to detect aCL IgG/IgM and anti-β2GPI IgG/IgM. We established distinct moderate and high semi-quantitative thresholds for CIA corresponding to ELISA. Additionally, we computed the likelihood ratios at various thresholds and compared them with ELISA. The qualitative agreement and quantitative correlation between CIA and ELISA were robust. When applying the established moderate and high thresholds of aCL/aβ2GPI IgG/IgM in CIA according to the equal ROC specificity corresponding to ELISA, the diagnostic efficiency and risk stratification capabilities of CIA aligned comparably with those of ELISA. Although IgM exhibited poorer performance in risk assessment compared to IgG, it still played as risk factors for thrombosis and obstetrical manifestations. Utilizing the established moderate/high thresholds for aCL/aβ2GPI IgG/IgM by CIA, effectively addressing both diagnostic and risk stratification requirements comparable to ELISA, signifies that the CIA has emerged as an alternative for aPL detection. The high specificity and clinical relevance of aCL/aβ2GPI IgM in clinical events highlight its importance in clinical practice.

ObjectivesThis study aims to evaluate the utility of the 2023 ACR/EULAR antiphospholipid syndrome (APS) classification criteria in identifying primary APS patients at high risk of complications.MethodsIn this single-center study, primary APS patients were classified according to both the revised Sapporo criteria and the 2023 ACR/EULAR criteria. The risk of complications was assessed using the adjusted Global Antiphospholipid Syndrome Score (aGAPSS).ResultsForty-five patients (73% females, median age 49 years) were included. Thirty-six patients met the 2023 ACR/EULAR criteria, all of whom also fulfilled the revised Sapporo criteria. Additionally, four out of nine patients not meeting the 2023 ACR/EULAR criteria satisfied the revised Sapporo criteria. Agreement rate between the two classification criteria was 91%, with a Cohen's kappa index of 0.66.Patients meeting the 2023 ACR/EULAR criteria had significantly higher aGAPSS scores compared to those who did not (13, 8–13 vs. 3, 0–5; p = 0.005). Furthermore, 55% of patients meeting the 2023 ACR/EULAR criteria were categorized as high risk based on aGAPSS scores, while those not meeting the criteria were predominantly categorized as low risk (77%). Interestingly, patients not meeting the 2023 ACR/EULAR criteria but fulfilling the revised Sapporo criteria had significantly higher aGAPSS scores compared to those not meeting either set of criteria (7, 5–13 vs. 0, 0–1.5; p = 0.015).ConclusionThe 2023 ACR/EULAR criteria effectively identify primary APS patients at increased risk of complications, as indicated by the aGAPSS score.Key Points• Identifying primary APS patients at high risk of complications remains a significant challenge.• The 2023 ACR/EULAR criteria show a correlation with the aGAPSS score, exhibiting the highest correlation with laboratory domains and minimal correlation with clinical domains.• The 2023 ACR/EULAR classification criteria are effective in identifying primary APS patients at high risk of complications.

The antiphospholipid syndrome is an autoimmune disorder of hypercoagulability characterized by the presence of autoantibodies to various phospholipids or phospholipid-binding proteins. The autoantibodies include anticardiolipin antibodies, lupus anticoagulant antibodies, and antibodies to β 2 -glycoprotein I (a phospholipid-binding protein). These autoantibodies have both procoagulant and anticoagulant effects, but the procoagulant effects predominate, resulting in syndromes of venous and arterial thrombosis and pregnancy loss. Antiphospholipid antibodies are a family of autoantibodies that exhibit a broad range of target specificities and affinities, all recognizing various combinations of phospholipids, phospholipid-binding proteins, or both. The term “antiphospholipid syndrome” was first coined to denote the clinical association between antiphospholipid antibodies and a syndrome of hypercoagulability. 1 , 2 Revision of the criteria for diagnosis of the antiphospholipid syndrome and the terminology used to describe the disease is an ongoing process 3 (Table 1). Background The first antiphospholipid antibody, a complement-fixing antibody that reacted with extracts from bovine hearts, was detected in patients with syphilis in 1906. 10 The relevant antigen was later . . .

The term ‘catastrophic’ antiphospholipid syndrome (APS) is used to define an accelerated form of APS resulting in multiorgan failure. Although catastrophicAPS patients represent less than 1% of all patients with APS, they are usually in a life-threatening medical situation that requires high clinical awareness. The careful and open discussion of several proposals by all participants in the pre-symposium workshop on APS consensus, held in Taormina on occasion of the 10th International Congress on aPL and chaired by Munther A Khamashta and Yehuda Shoenfeld (29 September 2002), has allowed the acceptation of a preliminary set of classification criteria. On the other hand, the optimal management of catastrophicAPS must have three clear aims: to treat any precipitating factors (prompt use of antibioticsif infection is suspected, amputation for any necrotic organ, high awareness in patients with APS who undergo an operation or an invasive procedure), to prevent and to treat the ongoing thrombotic events and to suppress the excessive cytokine ‘storm’. Anticoagulation (usually intravenous heparin followed by oral anticoagulants), corticosteroids, plasma exchange, intravenous gammaglobulins and, if associated with lupus flare, cyclophosphamide, are the most commonly used treatments for catastrophic APS patients.

Antiphospholipid syndrome (APS) is an autoimmune disorder for which there are no universally accepted diagnostic criteria, although classification criteria do exist, as is the case with most autoimmune diseases. Until 2023, the 2006 Sydney classification criteria were in use. Although originally intended for research purposes, these criteria have often been employed in clinical practice as a substitute for diagnostic guidelines, thereby conflating classification with diagnosis. In July 2023, ACR and European Alliance of Associations for Rheumatology convened a panel of experts to revise these criteria. The newly published classification criteria are explicitly intended for research use only. They place a strong emphasis on specificity—99%—but this comes at the expense of sensitivity—84%. The updated criteria encompass six clinical domains and two laboratory domains. Notably, the inclusion of new clinical features, such as thrombocytopenia, cardiac valve involvement and microvascular thrombosis, has broadened patient inclusion and, indirectly, aided the diagnostic process. However, a significant proportion of patients with suspected antiphospholipid antibody-related conditions may no longer meet the criteria for APS classification. In real-world settings, this could result in these individuals being denied appropriate management, thereby increasing their risk of subsequent thrombotic or obstetric events, as has already been demonstrated.This manuscript examines the advantages and limitations of the new clinical and laboratory domains, considering their implications not only from a research but also from a clinical perspective, APS.

Abstract Objectives Anti-β2 glycoprotein I domain I (anti-domain I) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies are present in patients with antiphospholipid syndrome (APS); however, their use in evaluation remains unclear. Methods Diagnostic attributes of lupus anticoagulant (LAC), anti-domain I IgG, anti-cardiolipin, anti-β2 glycoprotein I (anti-β2GPI), and aPS/PT IgG and IgM antibodies were assessed in 216 patients evaluated for APS. Results LAC had the best odds ratio (OR, 14.2) while that for anti-domain 1 IgG was comparable to anti-β2GPI IgG (OR, 8.3 vs 9.4) but higher than all others. Significant correlations were observed for thrombosis (P = .03) and pregnancy-related morbidity (P = .001) with anti-domain IgG and for any thrombosis with aPS/PT IgG (P = .006). Use of noncriteria antiphospholipid with or without criteria markers did not significantly increase the probability to diagnose APS. Conclusions Noncriteria tests can contribute to diagnosis and stratification of APS but do not improve diagnostic yield. Optimal strategies for implementation require prospective investigation.

Current classification criteria for definite antiphospholipid syndrome (APS) mandate the use of one or more of three positive ‘standardized’ laboratory assays to detect antiphospholipid antibodies (aPL) (viz: anticardiolipin [aCL] IgG and IgM; anti-β2glycoprotein I [anti-β2GPI] antibodies IgG and IgM; and/or a lupus anticoagulant [LAC]), when at least one of the two major clinical manifestations (thrombosis or pregnancy losses) are present. Although, efforts of standardization for these ‘criteria’ aPL tests have been conducted over the last 27 years, reports of inconsistencies, inter-assay and inter-laboratory variation in the results of aCL, LAC, and anti-β2GPI, and problems with the interpretation and the clinical value of the tests still exist, which affect the consistency of the diagnosis of APS. A Task Force of scientists and pioneers in the field from different countries, subdivided in three working groups, discussed and analyzed critical questions related to ‘criteria’ aPL tests in an evidence-based manner, during the 13th International Congress on Antiphospholipid Antibodies (APLA 2010, April 13–16, 2010, Galveston, TX). These included: review of the standardization and the need for international consensus protocol for aCL and anti-β2GPI tests; the use of monoclonal and/or polyclonal standards in the calibration curve of those tests; and the need for establishment of international units of measurement for anti-β2GPI tests. The group also reviewed the recently updated guidelines for LAC testing, and analyzed and discussed the possibility of stratification of ‘criteria’ aPL tests as risk factors for APS, as well as the clinical value of single positive vs. multiple aPL positivity. The group members presented, discussed, analyzed data, updated and re-defined those critical questions at a preconference workshop that was open to congress attendees. This report summarizes the findings, conclusions, and recommendations of this Task Force.

Objective: To describe the characteristics of patients with catastrophic antiphospholipid syndrome (APS) included in the International Registry of patients with this condition (CAPS registry) and to analyse the value of the recently proposed preliminary criteria for the classification of catastrophic APS. Methods: A review of the first 220 patients included in the website based CAPS registry was undertaken and the preliminary criteria for their classification were tested; 175 unselected patients with systemic lupus erythematosus or APS, or both, acted as controls. Results: The mean age of the patients was 38 (14) years (range 7 to 74), with a female preponderance (F/M, 153/67). The main clinical manifestations included renal involvement in 154 (70%), pulmonary in 146 (66%), cerebral in 133 (60%), cardiac in 115 (52%), and cutaneous in 104 (47%); 114 patients (52%) recovered after the catastrophic APS event (mortality 48%). Patients who received the combination of anticoagulation plus steroids plus plasma exchange or intravenous immunoglobulins had the best survival rate (63%, p = 0.09). Sufficient data could be analysed for application of the classification criteria in 176 patients. According to the preliminary criteria, 89 patients (51%) could be classified as having “definite” and 70 (40%) as having “probable” catastrophic APS, thus given a sensitivity of 90.3% with a specificity of 99.4%. Positive and negative predictive values were 99.4% and 91.1%, respectively. Conclusions: The preliminary criteria for the classification of catastrophic APS and the CAPS registry are useful tools for epidemiological studies.

The Task Force on Catastrophic Antiphospholipid Syndrome (CAPS) aimed to assess the current knowledge on pathogenesis, clinical and laboratory features, diagnosis and classification, precipitating factors and treatment of CAPS. This article summarizes the main aspects of its final report.