Development of clinical manifestations in individuals positive for antiphospholipid antibodies according to the 2023 ACR/EULAR serological domains.

Given the persistently high rates of adverse pregnancy outcomes (APOs) in women with antiphospholipid syndrome (APS) despite standard therapy, updated guidance is needed to support individualized care. This review summarizes current understanding of the obstetric management of APS, including pathogenic mechanisms, preconception evaluation, pregnancy management, and emerging therapeutic approaches. Recent studies reinforce the central role of inflammation, rather than thrombosis alone, in APS-related pregnancy morbidity. This evolving paradigm has prompted interest in immune-modulating strategies alongside conventional treatment. Early prospective data suggest that TNF-α inhibition may significantly reduce APOs in pregnant women with APS. Animal studies demonstrate immunomodulatory effects of statins at the maternal-fetal interface, although human evidence regarding statins remains limited. Updated clinical recommendations also clarify management surrounding assisted reproductive technology, emphasizing the importance of preconception antiphospholipid antibody screening and risk-based thromboprophylaxis to mitigate complications during ovarian stimulation and early pregnancy. Obstetric APS remains a major cause of maternal-fetal morbidity. Advances in understanding placental inflammation have expanded potential therapeutic targets, but standardized treatment remains limited. Optimal care requires risk-stratified, multidisciplinary management and further research to improve pregnancy outcomes.

Low-dose aspirin (LDA) is widely recommended to prevent hypertensive disorders of pregnancy (HDP). However, the evidence of its effectiveness in pregnancies with systemic lupus erythematosus (SLE) remains limited. This study evaluated the efficacy of LDA in preventing HDP in women with SLE. We conducted a retrospective cohort study of 124 pregnancies with SLE managed at our hospital. Pregnancy outcomes were compared between women treated with LDA and those not treated, using propensity score and inverse probability weighting analyses to adjust for confounders. LDA was used in 65 pregnancies and not used in 59. HDP occurred in 7/65 (10.8%) and 8/59 (13.6%), respectively. After adjusting for potential confounders, including antiphospholipid antibodies, lupus nephritis, chronic hypertension, chronic kidney disease, history of HDP, and hydroxychloroquine use, the risk ratio for HDP with LDA was 0.76 (95% confidence interval: 0.25-2.33; p=0.64). Sensitivity analysis was consistent. LDA did not significantly reduce the incidence of HDP in women with SLE. This lack of effect may reflect the low event rate in a well-controlled cohort. These findings underscore the need for individualized risk assessment and careful monitoring, beyond reliance on LDA alone, in the management of pregnancies with SLE.

Antiphospholipid antibodies (aPL) are directed against phospholipids and phospholipid-binding proteins. Laboratory assays used to detect aPL include serological tests for aPL against β2-glycoprotein 1, cardiolipin and other molecules, as well as functional assays for lupus anticoagulant. The presence of aPL can lead to endothelial dysfunction or a hypercoagulable state through prothrombotic and antifibrinolytic mechanisms. These processes, often in conjunction with a 'second hit', such as trauma, surgery, or other causes of hypercoagulability or stasis, can lead to venous or arterial thrombosis. The thrombotic risk associated with aPL is best recognized in thrombotic antiphospholipid syndrome, characterized by a persistently positive test for lupus anticoagulant or seropositivity for aPL associated with venous, arterial or microvascular thrombosis. However, aPL seropositivity and its clinical effect on thrombotic events have been increasingly recognized in a broader group of individuals who do not meet traditional research criteria for thrombotic antiphospholipid syndrome. In this Review, we provide an overview of the evidence related to aPL seropositivity in individuals with or without previous thrombosis and the clinical relevance of aPL seropositivity in predicting the risk of thrombotic cardiovascular events. We discuss potential management strategies and identify key knowledge gaps that warrant further research.

ObjectivesPsychosis is a rare but severe neuropsychiatric manifestation of systemic lupus erythematosus (SLE). Its prevalence, clinical predictors, and immunopathogenesis remain incompletely understood. This study aimed to estimate the prevalence of psychosis in adult SLE patients and identify associated clinical and immunological risk factors.MethodsThis systematic review and meta-analysis was conducted following PRISMA guidelines. A comprehensive search of PubMed, Embase, and the Cochrane Library was conducted to identify all relevant studies with ≥10 adults through November 2024. Case-series, case reports, narrative reviews and conference abstracts were excluded. Quality assessment employed the Cochrane Risk of Bias Tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. Statistical analysis was performed using the random-effects model, with heterogeneity assessed via I2 statistics.ResultsA total of 65 studies, comprising 31,495 SLE patients, were included. The pooled prevalence of psychosis in SLE patients was 4.5% (95% CI: 3.6%-5.5%) and 20.5% (95% CI: 10.0%-37.6%) among neuropsychiatric SLE (NPSLE) patients. Psychosis frequently occurred within 2 years of SLE onset and was strongly associated with higher SLE disease activity, positive anti-ribosomal P antibodies, antiphospholipid antibodies, and complement consumption. Delusions and hallucinations predominated among clinical presentations. Heterogeneity among studies was substantial.ConclusionObservational studies have reported that psychosis in SLE is strongly associated with increased disease activity and immune dysregulation. Anti-ribosomal P antibodies demonstrate a high negative predictive value, offering a valuable diagnostic adjunct. Recognition of psychosis may prompt closer clinical evaluation and, where appropriate, consideration of immunosuppressive treatment.

Acute coronary syndrome (ACS), driven by inflammation and thrombosis, remains a leading cause of morbidity globally. While traditional risk scores are useful, the prognostic value of combining inflammatory and autoimmune biomarkers remains understudied. This study aimed to evaluate the predictive role of high-sensitivity C-reactive protein (hs-CRP), platelet factor 4 (PF4), D-dimer, and antiphospholipid antibodies (anticardiolipin and anti-β2-glycoprotein I) for the development of major adverse cardiovascular events (MACE) in patients with ACS. We conducted a prospective cohort study at a tertiary referral center in Mexico. A total of 103 patients admitted with confirmed ACS were included. Blood samples were collected upon admission to measure biomarker levels. Participants were followed for 30 days. The primary outcome was the occurrence of MACE, defined as reinfarction, death, percutaneous coronary intervention, or bypass surgery. Multivariate logistic regression analysis was performed to identify independent predictors, adjusting for age, smoking, and comorbidities. MACE occurred in 51.4% of participants. Patients with adverse outcomes were significantly older and had longer hospital stays (p < 0.05). In the biomarker analysis, PF4 and hs-CRP demonstrated high sensitivity (98%) but low specificity. In the multivariate analysis, IgG anti-β2-glycoprotein I (p < 0.001) and D-dimer (p = 0.024) emerged as significant independent predictors of MACE. Conversely, IgM isotypes did not show independent predictive value. Beyond traditional risk factors, markers of coagulation (D-dimer) and autoimmunity (IgG anti-β2-glycoprotein I) are independent predictors of short-term adverse events in ACS patients. Integrating these multidomain biomarkers into clinical assessment may enhance risk stratification and prognostic accuracy.

Reduction of regulatory B cells is associated with high-risk clinical stratification in antiphospholipid syndrome patients.

Antiphospholipid antibodies (aPLs) are closely associated with recurrent spontaneous abortion (RSA) and adverse pregnancy outcomes (POs). Non-criteria aPLs may aid in diagnosing seronegative aPL-related RSA, but their limited performance often leads to missed or delayed diagnosis. This study aimed to improve diagnostic and predictive accuracy by integrating criteria and non-criteria aPLs with machine learning (ML) algorithm. In this multicenter prospective study, 1,321 participants were recruited and 751 included. Fifteen aPLs were measured using chemiluminescence immunoassay. Six ML algorithms were trained, and the optimal model was evaluated using the area under the curve (AUC), calibration curves, decision curve analysis (DCA), and Shapley additive explanations (SHAP). Using the 95th percentile as the cut-off, aPL positivity ranged from 2.62 to 12.13 % in pregnant woman with a history of RSA and 4.29-19.74 % in non-pregnant woman with a history of RSA. The light gradient boosting machine (LGBM) model achieved AUCs of 0.875 (pregnant) and 0.778 (non-pregnant) for RSA prediction, while the random forest (RF) model achieved an AUC of 0.885 for PO prediction-surpassing all single indicators (AUC 0.516-0.647). Calibration, DCA, and SHAP analyses demonstrated strong clinical utility. The ML models substantially improved diagnostic and predictive performance for RSA and PO. The LGBM and RF models showed the best accuracy and may serve as auxiliary diagnostic and early warning tools. Larger external cohorts are needed for further validation.

Cardiovascular risk factor control in antiphospholipid syndrome, and differences between primary and systemic lupus erythematosus-related antiphospholipid syndrome (SURF-SLE and APS project): a cross-sectional study of 1003 individuals from 11 countries.

A high risk of thrombosis is linked to myeloproliferative neoplasm (MPN) and antiphospholipid syndrome (APS). The systemic autoimmune disorder known as APS is characterized by persistently positive antiphospholipid antibodies [anticardiolipin (aCL), lupus anticoagulant, and antibeta 2 glycoprotein 1 IgG and IgM antibodies] in conjunction with obstetrical complications or thrombosis (Chayoua et al.). Polycythemia vera (PV) is a MPN that causes too many red blood cells (RBCs) in the blood and proinflammatory cytokines. In this report, we present a case of a 25-year-old lady with a history of second-trimester abortion who presented with abdominal pain and hepatosplenomegaly. Owing to erythrocytosis, thrombocytosis, and moderate hepatosplenomegaly, workup for MPN was done along with prothrombotic workup including APS, and she turned out to be positive for both. Coexistence of MPN and APS is rare in the literature. The optimal management of patients with coexistent APS and MPN has not been defined so far. Immediate anticoagulation with specific treatment for MPN is essential to prevent further thromboembolic episodes and progression to catastrophic APS.

Antiphospholipid syndrome (APS) is an acquired coagulation disorder with an unclear pathogenesis, diagnosed in the presence of thrombotic events, obstetric complications, or non-thrombotic manifestations, alongside persistently detectable antiphospholipid antibodies. aPLs seroconversion, defined as the transition from persistent antibody positivity to sustained antibody negativity, is typically confirmed by at least two negative tests ≥12weeks apart and maintained for over one year. This phenomenon is distinct from seronegative APS (SNAPS), in which patients present with APS-like clinical features but never fulfill laboratory criteria. Thrombotic risk remains significant in APS, particularly in patients with prior events or persistently elevated aPLs titers. Immunomodulatory therapies, such as hydroxychloroquine, rituximab, eculizumab, sirolimus, or other agents, may reduce antibody levels and contribute to improved outcomes, though evidence is limited. Among these, hydroxychloroquine is the most established agent, particularly in refractory or recurrent thrombotic cases, and is recommended as adjunctive therapy alongside anticoagulation in high-risk thrombotic and obstetric APS. While these therapies may allow cautious adjustments in anticoagulation for low-risk patients, anticoagulants should not be discontinued solely based on seroconversion or adjunctive treatment. Overall, immunomodulatory drugs should be considered strictly as adjuncts, with patient selection guided by clinical phenotype, thrombotic risk, and available evidence.

Obstetric antiphospholipid syndrome: Advances in pathogenesis.

Molecular determinants of allosteric modulation of protein disulfide isomerase by small-molecule b'-ligands.

Current status of cardiovascular risk factor control in antiphospholipid syndrome: where are we now?

Histopathological placental findings in antiphospholipid antibody carriers with a fetal loss beyond 12 weeks of pregnancy.

Sudden cardiac arrest due to a non-aneurysmal thrombus of the sinus of Valsalva: An unusual presentation of antiphospholipid syndrome

There is a lack of high-quality data to inform risk-stratified long-term thrombosis prevention strategies in patients with persistently positive antiphospholipid antibodies (aPL). We aimed to determine independent clinical and biologic predictors of thrombosis among persistently aPL-positive patients. Patients positive for aPL according to the Revised Sapporo Classification Criteria are eligible for inclusion in the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Registry. Registrants with at least 1 year of follow-up were included in this study. We fit Cox proportional hazards models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for independent predictors of thrombosis. In unadjusted analyses, based on 1067 patients with a mean follow-up of 4.43 years (4,727 person-years), history of thrombosis, hematologic disease (autoimmune haemolytic anaemia and/or thrombocytopenia), microvascular disease, obesity, renal disease, sedentary lifestyle, baseline anticoagulant use, and family history of early cardiovascular disease occurred more frequently (P < .05) among patients with new thrombosis (n = 93) than among those without new thrombosis (n = 974). After adjustment, independent predictors of new thrombosis were history of thrombosis (HR 2.34, 95% CI 1.14 to 4.81, P = .02) and hematologic disease (HR 1.95, 95% CI 1.19 to 3.18, P = .01); there was a trend for history of microvascular disease (P = .06) and obesity (P = .08). In this prospective analysis, history of thrombosis and hematologic disease each conferred an approximately twofold increased risk of new thrombosis in persistently aPL-positive patients. These findings can guide future clinical trial designs and inform patient management decisions.

Ultrastructural Injury of Renal Podocytes in Catastrophic Antiphospholipid Syndrome

Myocardial infarction in children is an infrequent phenomenon. Here, we are reporting a case of paediatric systemic lupus erythematosus with autoimmune haemolytic anaemia and anti-phospholipid syndrome who presented with complaints of chest pain. We have discussed the approach, evaluation and treatment using the example of this case.

Given the high incidence of secondary antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE) and the similarity of clinical manifestations between APS and SLE, validating the 2023 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) antiphospholipid syndrome (APS) classification criteria within this special population is of critical importance. This study aimed to clarify the clinical applicability of the 2023 criteria for classifying secondary APS in Chinese SLE populations. SLE patients with available data of antiphospholipid antibodies were retrospectively identified from the Peking University First Hospital Treat SLE to Target (STAR) cohort starting from April 1, 2007. This study included the patients from STAR between April 1, 2007 and May 1, 2024. Patients were independently classified according to both the 2023 criteria and 2006 criteria. For the 2023 criteria, two strategies were implemented (all-in or all-out) to determine whether overlapping manifestations of APS and SLE should be scored as APS when clinical differentiation was not feasible. The "gold standard" for APS classification was independently established by two rheumatologists. Sensitivity and specificity were compared between the two criteria. Subgroup analyses were conducted in terms of gender, age, body mass index, disease duration, and comorbidities. A total of 1001 SLE patients were included in this study. According to the two scoring strategies, if all overlapping features were considered as APS manifestations, 101 patients (10.1%) met the 2023 criteria, which showed higher sensitivity (0.878 vs. 0.768) but lower specificity (0.968 vs. 0.988) compared to the 2006 criteria. When overlapping features were excluded from APS scoring, 68 patients (6.8%) met the 2023 criteria, which demonstrated similar specificity (0.993 vs. 0.988) but lower sensitivity (0.756 vs. 0.768) compared to the 2006 criteria. The sensitivity and specificity of 2023 APS classification criteria varied depending on the scoring strategy used. Considering the presence of SLE as a distinct item in future APS classification criteria may be warranted.