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Abstract: Few studies have prospectively evaluated the incidence and outcomes in children with provoked venous thromboembolism (VTE) and transient or persistent antiphospholipid antibodies (aPLs). We compared outcomes of patients aged <21 years with a first-episode acute provoked VTE and positive aPL at diagnosis, enrolled in the Multicenter Evaluation of the Duration of Therapy for Thrombosis in Children trial. aPLs were tested at enrollment and, when positive, repeated at 6 weeks after VTE diagnosis. Subsequent testing was performed at the discretion of the treating hematologist. Of 524 patients, 116 (22%) had positive aPLs at enrollment. At follow-up, 70 (60%) had transient (n = 66) or low-titer aPLs (n = 4), 11 (10%) had persistent aPLs meeting the criteria for antiphospholipid antibody syndrome (APS), and 35 (30%) had no repeat testing. Patients with APS were older (15.8 vs 9.9 years; P = .014) and had a statistically significant higher risk of symptomatic recurrent VTE (18% vs 1%; odds ratio [OR], 12.2; 95% confidence interval [CI], 1.4-108; P = .025) and a statistically nonsignificant but clinically meaningful difference in the risk of anticoagulant-related clinically relevant bleeding (9% vs 0%; OR, 20.1; 95% CI, 0.7-558; P = .077) compared with those in the transient or low-titer aPL group. In conclusion, aPLs are common in young patients with acute provoked VTE and are mostly transitory and clinically insignificant. Patients with APS and provoked VTE appear to have an increased risk of recurrent VTE compared with patients with transitory or low-titer aPLs. Future collaborative studies should investigate the optimal VTE management for children with provoked VTE who meet the criteria for APS. The trial was registered at www.ClinicalTrials.gov as #NCT00687882., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Rationale: Antiphospholipid antibody syndrome and protein S/C deficiency are diseases that are sometimes complicated by thrombus, and heparin-induced thrombosis (HIT) has also been reported., Patient Concerns: A male patient in his 60s with elevated D-dimer and superior mesenteric thrombus and portal vein thrombus underwent partial small intestine resection and thrombectomy. After administration of heparin, aortic thrombosis and pulmonary embolism occurred along with rapid thrombocytopenia., Diagnosis: The patient was diagnosed with HIT combined with protein S deficiency and antiphospholipid antibody syndrome., Interventions and Outcomes: Heparin administration was discontinued, and plasma exchange with fresh frozen plasma replacement and argatroban administration were started. These treatments reduced D-dimer, restored platelet counts, and improved thrombosis., Lessons: Although HIT alone can cause severe arteriovenous thrombosis, our case suggests that it is important to search for the underlying procoagulant factors., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Larsen's syndrome is an exceedingly rare and debilitating skeletal disorder characterized by multiple bony deformities and joint contractures. A 47-year-old female grappled with its severe manifestations, including functional quadriplegia, limb atrophy, and various orthopedic surgeries. This is the only reported case of the concurrent presence of antiphospholipid antibody syndrome (APLA) and Larsen's syndrome. While Larsen's syndrome's genetic underpinnings are known to involve filamin B (FLNB) gene mutations, this patient's distinct presentation and complex clinical history added layers of intrigue. Intriguingly, APLA predisposes individuals to thrombotic events, but the patient's manifestation with rectal bleeding with normal coagulation parameters introduced an unexpected twist. Despite the absence of clear causative links, this case highlights the rarity of encountering Larsen's syndrome and APLA concurrently. Their potential interactions and mutual influence remain largely unexplored, underscoring the need for more research in this domain. Intricacies also emerged in the management of APLA within a surgical context. The decision to transition between anticoagulants underscores the necessity of individualized and comprehensive care for patients grappling with multiple comorbidities. It raises questions about the potential overlap between Larsen's syndrome and connective tissue diseases, like Marfan's syndrome, that warrant further exploration. The case also emphasizes the significance of increased patient mobilization to prevent thrombotic events in those who are bedridden or wheelchair-bound. This extremely unique presentation, featuring a genetic skeletal disorder, an autoimmune condition, recurrent diaphragmatic hernias, and a colon polyp-induced hemorrhage, beckons further research and analysis to unravel any potential associations between these conditions., (© Journal of the Association of Physicians of India 2024.)

Background: Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and adverse pregnancy outcomes, often associated with elevated antiphospholipid antibodies (aPLs). The 2023 ACR/EULAR criteria for APS necessitate persistent medium to high titers of aPLs for laboratory confirmation. However, the impact of persistently low-titer aPLs in recurrent miscarriage (RM) patients remains controversial. This study aims to analyze the effect of treatment on pregnancy outcomes and maternal-fetal complications in patients with low-titer aPLs., Methods: The study encompassed 252 pregnancies in 237 RM patients tested for aPLs at the Third Hospital of Guangzhou Medical University from January 2018 to July 2022. Patients were divided into two groups based on aPLs titers: 86 with low-titer aPLs (92 pregnancies) and 151 aPLs-negative (160 pregnancies). Of the low-titer group, 71 received treatment, while 21 and all aPLs-negative patients did not. Seventy-one treated patients with low-titer aPLs were divided into two groups. Group A (n = 15) received a standard treatment regimen that included low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH). In contrast, Group B (n = 56) received a multidrug regimen, which included hydroxychloroquine (HCQ) and/or glucocorticoids (GC) and/or intravenous immunoglobulin (IVIG) in addition to the standard treatment of LDA and LMWH. Pregnancy outcomes and maternal-fetal complications were subsequently compared., Results: The highest positivity rates were for aCL-IgM (76.2% in the untreated low-titer aPLs group and 81.7% in the treated low-titer aPLs group), followed by aβ2GPI-IgM (23.8% in the untreated low-titer aPL group and 11.4% in the treated low-titer aPLs group), and LA (5.6% in the untreated low-titer aPLs group and 3.3% in the treated low-titer aPLs group). Single antibody positivity was 90.5% in the untreated low-titer aPL group and 87.3% in the treated low-titer aPLs group, with double positivity at 9.5% in the untreated low-titer aPLs group and 12.7% in the treated low-titer aPLs group. No triple positivity was detected. The treated low-titer aPLs group had more previous miscarriages (p < 0.05) and a higher ANA positivity rate (p < 0.05) than the aPLs-negative group. Additionally, the treated low-titer aPLs group had lower complement levels than the aPLs-negative group. Immunoglobulin IgM levels were higher in both the untreated and treated low-titer aPL groups compared to the aPLs-negative group (p < 0.05). Post treatment, the live birth rate in the low-titer group significantly exceeded that of the untreated group (67.6% vs. 33.3%; p = 0.005). The miscarriage rate was notably lower in untreated low-titer patients compared to aPLs-negative patients (32.4% vs. 66.7%; p = 0.005). No significant differences were observed in maternal or fetal complications between the groups. In the standard treatment group (Group A), there were 8 (53.3%) live births, whereas the multidrug treatment group (Group B) had 40 (71.4%) live births, a significantly higher rate than in the standard treatment group, although the difference lacked statistical significance., Conclusions: The study indicates that untreated RM patients with low-titer positive aPLs have a higher recurrence of miscarriage compared to the aPLs-negative RM group. However, recurrence significantly decreases following appropriate intervention, suggesting the benefits of treatment for RM patients with low-titer aPLs., (© 2024 The Author(s). American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Background: Primary antiphospholipid syndrome (PAPS) has been associated with an increase in clinical events associated with atherosclerotic vascular disease. Intima media thickness (IMT) of carotid arteries is a surrogate marker of atherosclerotic vascular disease., Objectives: To conduct a systematic review and meta-analysis of studies evaluating IMT and their clinical correlates in PAPS., Methods: Systematic search of EMBASE and PubMed databases from January 2000 to December 2023; we employed random effect meta-analyses for continuous outcomes and Peto's odds ratio for rare events., Results: The meta-analysis included 21 studies (20 case control and 1 cohort) showing that PAPS patients (n = 1103) had thicker IM than controls (n = 832) (p < 0.0001) with wide heterogeneity (I 2  = 86.9 %); PAPS patients (n = 782) also had a greater pooled prevalence of carotid plaques than controls (n = 537) (13.1 % vs 2.97 %, p < 0.0001). A sensitivity analysis by meta-regression indicated that mean age, gender, disease duration, lipid profile, blood pressures, smoking and statin use all explained the heterogeneity variance; a sensitivity analysis by subgroups confirmed smoking status and statin use as explanatory variables with the addition of ethnicity., Conclusion: Atherosclerosis of the carotid artery represents a clinical feature of PAPS in relation to the traditional risk factors and to statin use. Minimising the atherogenic risk with statins could reduce the late arterial atherothrombotic risks of PAPS., Competing Interests: Declaration of competing interest The authors have no financial or non-financial competing interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Antiphospholipid syndrome (APS) is an acquired autoimmune disorder characterized by distinct pathophysiological mechanisms leading to heterogeneous manifestations, including venous and arterial thrombosis. Despite the lack of specific markers of thrombosis risk in APS, some of the mechanisms responsible for thrombosis in APS may overlap with those of other thromboembolic diseases. Understanding these similarities is important for improving the assessment of thrombosis risk in APS. MicroRNAs (MiRNAs) are RNA molecules that regulate gene expression and may influence the autoimmune response and coagulation., Purpose: In this scoping review we aimed to investigate shared miRNAs profiles associated with APS and other thromboembolic diseases as a means of identifying markers indicative of a pro-thrombotic profile among patients with APS., Data Collection and Results: Through a comprehensive search of scientific databases, 45 relevant studies were identified out of 1020 references. miRs-124-3p, 125b-5p, 125a-5p, and 17-5p, were associated with APS and arterial thrombosis, while miRs-106a-5p, 146b-5p, 15a-5p, 222-3p, and 451a were associated with APS and venous thrombosis. Additionally, miR-126a-3p was associated with APS and both arterial and venous thrombosis., Conclusion: We observed that APS shares a common miRNAs signature with non-APS related thrombosis, suggesting that miRNA expression profiles may serve as markers of thrombotic risk in APS. Further validation of a pro-thrombotic miRNA signature in APS is warranted to improve risk assessment, diagnosis, and management of APS., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Libman-Sacks endocarditis is a rare cardiac manifestation of anti-phospholipid syndromes, in which non-infectious thrombotic vegetations are found on the heart valves. Most patients are asymptomatic whereas the risk of thromboembolism is considerable. Diagnostic work-up is based on questioning and clinical examination data looking for extracardiac signs, biological data and also on imaging, and, above all, echocardiography. We report the case of a 47-year-old female patient with no known history who is admitted to hospital with paresthesia of the right hemi-body associated with dysarthria. Cerebral CT scan confirms a paraventricular ischemic stroke. The etiological work-up for stroke is negative except the transesophageal echocardiogram which reveals mitral valve vegetations. Further investigations lead to the diagnosis of Libman-Sacks endocarditis. Treatment with Coumadin is started, with a target INR of between 2 and 3, as recommended. The clinical course was favourable, with stable lesions on transoesophageal echocardiography carried out later., Competing Interests: Déclaration de liens d'intérêts Les auteurs déclarent n'avoir aucun lien d'intérêt en relation avec cet article., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objectives: This 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., Methods: In 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)., Results: Forty-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)., Conclusion: The 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., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Purpose: This study aimed to evaluate fetal left ventricular function (LVF) in pregnant women with obstetric antiphospholipid syndrome (OAPS) by Doppler ultrasound and developed a clinical nomogram to predict adverse perinatal outcomes., Methods: In this prospective observational study, 105 pregnant women were enrolled and divided into the OAPS cohort (n = 60) and the control cohort (n = 45). Fetal cardiac function parameters were collected and compared between two cohorts. Univariate and multivariate analysis was conducted to select the risk factors associated with adverse perinatal outcomes, and a clinical nomogram was developed based on these selected risk factors. The predictive performance of corresponding indicators for adverse perinatal outcomes was evaluated using receiver operating characteristic (ROC) curve analysis., Results: The OAPS cohort revealed an increase in the isovolumic relaxation time (IVRT) and myocardial performance index (MPI), a decrease in the ejection time (ET), middle cerebral artery pulsatility index (MCA-PI) and cerebroplacental ratio (CPR) compared to the control cohort. Through univariate and multivariate analysis, gravidity, CPR, and MPI were the risk factors associated with adverse perinatal outcomes. A model predicting adverse perinatal outcomes in OAPS pregnant women was constructed based on these three factors and visualized as a nomogram. The nomogram could accurately predict adverse perinatal outcomes with an area under the curve of 0.923 (95% CI: 0.858-0.982). This performance was better than evaluating individual factors such as MPI (0.825, 95% CI: 0.739-0.911) and CPR (0.816, 95% CI: 0.705-0.927) for efficacy., Conclusion: MPI can be used to assess fetal LVF and predict adverse perinatal outcomes. We developed a nomogram to predict adverse perinatal outcomes in OAPS women. This imaging-based evidence can provide timely clinical intervention, enabling personalized clinical decision-making., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Ovulation induction for in vitro fertilization (IVF) may increase intravascular thromboses among patients with antiphospholipid autoantibodies (aPLs) or antiphospholipid syndrome (APS) due to the high estrogen levels. While natural or modified natural IVF treatment cycles (MNC) are sometimes used instead of stimulated cycles with empiric anticoagulant treatment among these infertile patients, their efficacy is unclear., Materials and Methods: A retrospective cohort study including all IVF cycles of patients diagnosed with aPLs or APS in a tertiary, university-affiliated hospital between 2012 and 2022. The outcomes of stimulated cycles with anticoagulants and MNC and natural IVF cycle attempts were compared., Results: 121 oocyte retrievals from 38 women were analyzed: 93 stimulated and 28 MNC or natural IVF cycles. The rates of cycle cancellation (0 % vs. 17.9 %, p < 0.001) and cycles in which no oocytes were retrieved (0 % vs. 43.5 %, p < 0.001) were significantly lower following stimulated cycles vs. natural and MNC. In parallel, positive β-hCG (31.9 % vs. 10.9 %, p = 0.03), clinical pregnancy rate (23.6 % and 3.6 %, p < 0.001) and live birth rates (18.1 % vs. 3.6 %, p = 0.01) were significantly higher following stimulated cycles. No thrombotic events or bleeding occurred in any cycle., Conclusion: Ovarian stimulation for IVF is more effective for successful pregnancy and delivery than natural cycles and MNC and can be safely undertaken in aPLs or APS women undergoing IVF. Rates of complication from hormonal treatment are not increased when treated with LMWH during ovarian stimulation., Competing Interests: Declaration of competing interest We have confirmed that all manuscript authors contributed to the concept, design, results interpretation, and manuscript drafting. None of the authors of this study have any conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Vitamin-K antagonists (VKA) are considered the first-line anticoagulants for thrombotic antiphospholipid syndrome (TAPS), particularly with triple positivity or arterial events. However, thrombotic recurrence remains high despite anticoagulation and other clinical issues may arise. Long-term parenteral anticoagulants may therefore be considered, however little is known about the viability of fondaparinux in this setting., Materials and Methods: We describe the efficacy and safety of long-term fondaparinux for TAPS (>3-months duration) treated at a single centre in the UK. Clinical features and the outcomes of recurrence and bleeding were reviewed using electronic patient records., Results: 46 patients were identified with history of either venous or arterial TAPS and a total 175 patient-years using fondaparinux (median duration 2.7 years/patient (IQR 1.4-4.8)). 43 (93%) had VKA as first-line anticoagulation with a median duration of 6.5 years (IQR 4.0 - 9.8). All patients received fondaparinux as second-to fourth-line anticoagulation.Thrombosis recurrence occurred in 1 (1%) patient (0.6 events/100-patient years). Major, clinically relevant non-major (CRNM) or minor bleeding occurred in 2 (7%), 5 (10.9%) and 8 (17.4%) patients respectively. Major/CRNM bleeding rates were 1.1 and 2.9 events/100-patient-years. Age >65years was associated with bleeding ( p = .047) and concurrent antiplatelets were associated with major/CRNM bleeding ( p = .011). Logistic regression showed increasing age was associated with bleeding (OR = 1.097, p = .009)., Conclusions: We suggest that fondaparinux may be used for TAPS when VKA is not appropriate. Thrombotic recurrence was infrequent, and the number of major bleeding events appeared comparable to conventional therapies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Recurrent thrombosis is one of the main clinical features of antiphospholipid syndrome (APS), and recent studies revealed that APS shares similar pathophysiological mechanisms with atherosclerosis. Oxidised low-density lipoprotein (OxLDL) and antibodies against OxLDL (anti-OxLDL) are involved in the development of atherosclerosis. This study aims to investigate the clinical significance of OxLDL and anti-OxLDL in APS patients., Methods: One hundred and seventy APS patients and 39 healthy controls (HC) were enrolled. Clinical and laboratory data were collected from Clinical Data Center of Peking University People's Hospital. OxLDL and anti-OxLDL were detected using enzyme-linked immunosorbent assay., Results: Among the 170 APS patients, 106 had isolated thrombotic APS. Compared with HC, APS patients exhibited higher titres of OxLDL [413.86 (220.11-853.67) ng/mL vs. 45.54 (0-105.98) ng/mL, p<0.001] and anti-OxLDL [107.62 (75.68-174.18) U/L vs. 44.13 (18.44-79.76) U/L, p<0.001]. Also, APS patients exhibited a higher positivity rate for OxLDL (88.2% vs. 5.1%, p<0.001) and anti-OxLDL (84.1% vs. 36.5%, p<0.001) compared to HC. APS patients with elevated levels of OxLDL had a higher rate of LAC positivity (68.0% vs. 45.0%, p=0.042). Furthermore, APS patients with positive anti-OxLDL demonstrated a higher occurrence of venous thrombosis (46.2% vs. 18.5%, p=0.008) and a lower rate of Coomb's test positivity (52.6% vs. 76.2%, p=0.049). Multivariate logistic regression revealed that anti-OxLDL positivity (OR 12.424, 95%CI 1.108-139.330, p=0.041) were risk factors for venous thrombotic APS., Conclusions: This study indicates that the presence of anti-OxLDL may serve as potential markers for venous thrombosis in APS patients. OxLDL and anti-OxLDL may function as valuable biomarkers for monitoring APS.

Purpose: To present an atypical case of severe bilateral ocular toxoplasmosis with systemic involvement that initially mimicked an autoimmune etiology, posing challenges to its diagnosis and treatment., Case Report: A 39-year-old immunocompetent male was admitted to the hospital due to a presumed pulmonary thromboembolism concomitant with an abrupt onset of vision loss. Initial differential diagnoses included antiphospholipid syndrome and systemic lupus erythematosus, prompting the administration of corticosteroid pulses and rituximab. Despite observing a partial systemic response, there was no improvement in visual acuity. Subsequent aqueous humor polymerase chain reaction confirmed Toxoplasma gondii infection, leading to the introduction of oral antibiotic therapy. The patient's condition showed a partially favorable response; however, the treatment could not reverse the permanent retinal damage., Conclusion and Importance: This case underscores the importance of ruling out an infectious etiology in all cases of uveitis. Additionally, it alerts clinicians to the possibility that elevated positive autoantibodies may result from a severe inflammatory reaction caused by pathogens rather than an autoimmune or autoinflammatory disease, particularly in instances of poor treatment response or atypical clinical presentation.

Anti-phospholipid syndrome (APS) nephropathy is an autoimmune disease that is sometimes accompanied by systemic lupus erythematosus (SLE). Here, we report the use of rituximab to treat a case of APS nephropathy in a SLE patient with recurrent vascular thrombosis. A 52-year-old woman, who had been diagnosed with SLE 11 years earlier, was referred to a nephrology clinic for evaluation of azotaemia and proteinuria. She had experienced spontaneous abortion at 35 years of age. The patient had been diagnosed with right popliteal thrombosis at 39 years of age, and with left pulmonary artery thrombosis and SLE at 41 years of age. Before admission, she was undergoing anticoagulant and immunosuppressive therapies, with follow-up in the rheumatology clinic. At her last outpatient clinic visit before admission, she exhibited mild bilateral lower-limb pitting oedema, impaired renal function and proteinuria. Renal biopsy revealed arteriolar wall thickening, with thrombi in the capillary lumina and marked inflammatory cell infiltration in the interstitium. The patient was treated with warfarin and high-dose corticosteroids. Intravenous rituximab (500 mg) was also administered twice at a 4-week interval. Her renal function did not worsen any further, and her proteinuria decreased. Here we report the successful use of rituximab to treat APS nephropathy in a patient with SLE, who had progressive renal insufficiency., (© 2024 The Author(s). Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Antiphospholipid syndrome (APS) is a state of hypercoagulability due to persistent antiphospholipid antibodies (aPLs) in the blood. Catastrophic APS (CAPS) is a severe form with higher morbidity and mortality in which there occurs widespread thrombosis in multiple organs and hence warrants early diagnosis and aggressive management. We report a case of pediatric CAPS with extensive cutaneous involvement precipitated by infection successfully treated with the combination of high dose systemic corticosteroids, antibiotics, long-term anticoagulation, and wound care., (© 2024 Wiley Periodicals LLC.)

Objective: The purpose of the present study was to evaluate whether intravenous immunoglobulin (IVIG) increases live birth rates and improves neonatal results in patients with antiphospholipid antibodies (aPL) at high-risk for miscarriage., Background: Positivity of aPL in pregnant women is a high-risk factor for miscarriage, and IVIG treatment has emerged as a potential intervention., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was employed to search multiple electronic databases for articles published until August 20, 2023, including PubMed, Web of Science, Embase, Scopus and Medline. The inclusion criteria encompassed studies assessing the efficacy of IVIG in aPL-positive patients with a high risk of miscarriage. Relevant articles were assessed for the quality and data were extracted for analysis. Two independent reviewers performed study selection, data extraction, and quality assessments. The risk of bias was evaluated according to the Cochrane risk of bias tool. All analyses were conducted using Review Manager 5.3., Results: This systematic review included nine randomized controlled trials, with 366 aPL-positive women at high risk of miscarriage. These studies included in this review were randomized controlled trials. The primary outcome measures were successful pregnancy outcomes and live birth rates. The secondary outcomes included obstetric complications, and neonatal outcomes (such as birth weight and live-birth rate). The comparison between the intervention and control groups revealed no significant differences in terms of obstetric complications and neonatal outcomes. The group receiving IVIG treatment had a higher prevalence of preterm deliveries than controls (OR = 2.05, I 2 = 46%, 95% CI [0.58-5.24]), but also exhibited a partial improvement in live birth rates (OR = 2.86, I 2 = 52%, 95% CI [1.04-7.90]), because it reduced the number of miscarriages (OR = 0.35, I 2 = 52%, 95% CI [0.13-0.96])., Conclusion: Based on the available evidence, IVIG intervention appears to be a potentially effective approach for managing of aPL-positive pregnant women with high risk of miscarriage. While IVIG shows significant potential in tripling the chances of having a live-born child, further large-scale randomized controlled trials are necessary, preferably comparing IVIG with hydroxychloroquine or lifestyle and dietary interventions, to refine treatment protocols and ensure the most effective application., Competing Interests: The authors declare that they have no competing interests., (© 2024 Yuan et al.)

Objectives: The aim of this study is to assess the risk factors associated with thrombotic events in obstetric antiphospholipid syndrome (OAPS) patients and to develop a predictive model specifically tailored to predict the risk of postpartum thrombosis in OAPS patients without prior thrombotic events. This research seeks to enhance clinician's awareness regarding the postpartum care and monitoring of OAPS patients., Methods: A retrospective study was conducted at the First Affiliated Hospital of the Fourth Military Medical University including 269 consecutive inpatients diagnosed with antiphospholipid syndrome (APS) from July 1, 2008 to July 31, 2022. All participants met the 2006 Sydney APS classification criteria or the "non-criteria OAPS classification". Out of 98 candidate clinical and laboratory parameters considered, 40 potential variables were selected for analysis based on expert opinion. The logistic regression mode with the Least Absolute Shrinkage and Selection Operator (LASSO) were used to identify optimal predictive characteristics. All samples were included in the model building and a nomogram was generated based on these characteristics. The differentiation, calibration, and clinical utility of the predictive model were evaluated using the area under the curve (AUC), calibration curve, and decision curve analysis. The model was also validated by a 1000 bootstrap tests., Results: 126 patients with OAPS were enrolled, and a total of 89 OAPS patients who had never experienced thrombosis were retrospectively analyzed. After 3 years follow-up, 32.58% of the patients (29/89) developed thrombosis. In order to create, LASSO logistic regression identified three optimal variables: the platelet count less than 125×109/L, more than one positive aPLs (antiphospholipid antibody), and the use of low molecular weight heparin (LMWH) or low dose aspirin (LDA) after delivery. A predictive model was conducted using these three predictive indicators for patients with OAPS who experience thrombosis for the first-time. This prediction model has good distinction, good calibration, and fair clinical practicality., Conclusion: Our model has good predictive ability in assessing the risk of thrombosis in patients with OAPS without prior thrombotic events. This model is easy to predict, has good discriminability and calibration, and can be utilized as a routine tool for thrombus screening in OAPS patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gao, Zheng, Wang, Jia, Wan, Han, Zheng, Liu, Zheng, Wu and Zhu.)

Objectives: Chorea, characterised by involuntary, irregular movements, is a rare neurological manifestation of antiphospholipid syndrome (APS). The specific clinical features remain unclear. This study aimed to summarise the available evidence on antiphospholipid antibody (aPL)-associated chorea., Methods: We used a mixed-methods approach, combining data from patients with chorea with aPL positivity admitted to Peking Union Medical College Hospital (PUMCH) from 2014 to 2024, with cases identified in public databases since 1983. We collected and analysed clinical, laboratory, and imaging results, along with their treatments and outcomes., Results: A total of 180 patients with incident aPL-associated chorea were included (13 from PUMCH and 167 from the literature). The majority (81.7%) were female, with a mean age of chorea onset 22.8 years (SD=16.0). Chorea was the initial symptom in 87.9% of cases and often occurred as a single episode (67%), involving bilateral limbs (58.8%) and both upper and lower limbs (87.2%). 43.3% met the 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria. Thrombocytopenia (30.0%) and arterial thrombosis (29.1%) were the most common manifestations. Lupus anticoagulant was positive in 84.2% of patients, anticardiolipin IgG in 70.8%, and anti-β2 glycoprotein I IgG in 52.9%. Among those who had results available for the three tests, 57.6% were triple-positive. ANAs were positive in 63.6%. MRI revealed basal ganglia lesions in only 14.8% of patients, whereas all positron emission tomography (PET) scans showed contralateral striatal hypermetabolism. Treatment varied, with most receiving combination therapies of neuroleptics, anticoagulants, antiplatelets, steroids and immunosuppressants. Chorea completely or partially improved in 95.5% of patients., Conclusion: Chorea is a significant but under-recognised manifestation of APS, predominantly affecting young women and often presenting as the initial symptom. Characteristic PET findings of contralateral striatal hypermetabolism can assist in diagnosis. Treatments with glucocorticoids and immunosuppressive therapies appear beneficial. Further research is needed to understand the pathophysiology and optimise management strategies for aPL-associated chorea., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: Systemic lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis are chronic autoimmune diseases affecting women of childbearing age. These diseases may impair fertility and fecundity, as well as complicate pregnancy and the puerperium in these patients including disease flare and obstetric complications on both the maternal and fetal side. For each patient, an appropriate preconceptional counseling with risk stratification is required, including assessment of disease activity, organ involvement, serological profile, and comorbidities.In cases of pregnancy, the aims of treatment are to prevent disease activity, to treat disease activity in cases of flare, and to prevent maternal and fetal complications such as preeclampsia or fetal loss. In all patients with these diseases, close clinical monitoring during pregnancy and puerperium is mandatory. This review aims to summarize the fertility issues in patients with systemic lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis and to provide an update on pregnancy management and outcomes in these patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Systemic Lupus Erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which manifests as recurrent thrombotic events or obstetric complications in presence of antiphospholipid antibodies. Hereby we present a case of a child who presented with low grade fever, superficial thrombophlebitis with mucosal bleeding and was diagnosed as Lupus Anticoagulant Hypoprothrombonemia Syndrome (LAHS)., Case: A 7-year-old girl was hositalized with complaints of fever and spontaneous bleeding from gums and epistaxis. On examination, she had multiple small tender nodular lesions with greenish hue of overlying skin suggesting superficial thrombophlebitis and mild non-tender hepatosplenomegaly. Her coagulogram revealed normal platelet counts and deranged PT and APTT. ESR and CRP were raised. Serology for viral infections, blood and urine cultures were negative. Patient had persistent coagulopathy, mucosal bleeding and low-grade fever despite supportive treatment. She was tested for anti-nuclear antibodies (ANA) in view of suspicion of autoimmune process. ANA was positive in high titer with speckled pattern on indirect immunofluorescence. Mixing studies showed correction of PT and non-correction of APTT. PT based factors were normal except for prothrombin (FII) which was low and remained low despite dilution. APTT based factors (FVIII and FIX) were low but corrected on dilution. This was suggestive of prothrombin deficiency and a presence of a nonspecific inhibitor of APTT pathway (likely lupus anticoagulant). Presence of antiprothrombin antibodies established the diagnosis of LAHS. ENA profile was positive for SmD1, Ro60 and Ku. Complement levels were low. Direct Coomb's test was positive but there was no evidence of hemolysis. Lupus anticoagulant by DRVVT and anti-cardiolipin antibodies by ELISA were positive. Patient was diagnosed as Systemic Lupus Erythematosus with Lupus Anticoagulant Hypoprothrombinemia Syndrome. She was treated with IV methylprednisolone. Patient showed significant improvement in form of resolution of fever, mucosal bleeding, correction of deranged INR and reversal of hypocomplementemia. She was discharged on hydroxychloroquine, mycophenolate mofetil and tapering doses of prednisolone. On follow up, child was doing well and her prothrombin time and complement levels had normalized. Low dose aspirin was aspirin was added for thromboprophylaxis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Purpose of Review: This review offers an overview of the most important recent articles on pediatric APS., Recent Findings: Non-thrombotic extra criteria manifestations were prevalent in pediatric APS. Pregnancy morbidity has been described as the first manifestation of APS at youth age, impairing gestational outcomes. The 2023 APS criteria were developed for adult APS patients, and there is still a lack of pediatric-specific APS criteria. Catastrophic APS was more commonly reported as the initial manifestation of pediatric APS than in adults. Regarding treatment, direct oral anticoagulants have been recently approval for pediatric patients with venous thrombosis. New approaches have been proposed for severe cases, for arterial thrombosis, and rituximab for refractory cases. Recurrences typically occurred early and were associated with older age at diagnosis. Current studies highlighted the multifaceted nature of pediatric APS. Further large prospective multicenter studies evaluating new medications capable of reducing recurrence risk and improving prognosis in this population will be required., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Patients with Antiphospholipid Syndrome (APS) undergoing cardiopulmonary bypass (CPB) surgery are at increased risk for thrombotic and hemorrhagic complications. Anticoagulation during CPB is typically monitored with activated clotting time (ACT) which may be falsely prolonged in patients with APS. The Hepcon Hemostasis Management System quantitatively determines the whole blood heparin concentration through heparin/protamine titration., Methods: This was a retrospective study of APS patients who underwent cardiac surgery requiring CPB at the Cleveland Clinic between April 2013, and July 2020. The primary endpoint was the composite rate of hemorrhagic or thromboembolic complications per surgical case in patients monitored by Hepcon versus patients monitored by ACT. Secondary endpoints were median volume of chest tube output and packed red blood cell (PRBC) transfusion within the first three post-operative days., Results: 43 patients were included. 20 (47%) patients were monitored using Hepcon while 23 (53%) were monitored using ACT. For the primary endpoint of rate of thromboembolic or hemorrhagic complications per surgical case, there was no statistically significant difference between the Hepcon and ACT groups (HMS, 6/20 [30%]; ACT, 7/23 [30%]; p = >0.99). For the secondary endpoints, there was no statistically significant difference in median post-operative chest tube output (780 mL vs. 850 mL; p = 0.88) and median post-operative PRBC transfusion (1 unit vs. 0 unit; p = 0.28) between the Hepcon and ACT groups, respectively., Conclusion: There was no difference in the composite outcome of thrombotic or hemorrhagic complications in patients monitored by Hepcon versus those monitored by ACT., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Patrick Grady: Consultancy for Medtronic.

In celiac disease (CD) there is a state of hypercoagulability and multiple factors have been found that may be involved. Cases of association of CD and antiphospholipid síndrome (APS) have been described and several observational studies have found an increase in antiphospolipid antibodies (AAF) in patients with CD, so both entities may be interrelated, increasing the risk of thrombotic events. A descriptive case of a patient who is simultaneusly diagnosed with CD and APS is presented., (Copyright © 2024 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Competing Interests: Conflict of interest: None declared.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLA), such as anticardiolipin (aCL), anti-β2-glycoprotein I (aβ2GPI), or lupus anticoagulant (LA). Although cerebrovascular events are commonly associated with APS, comprehensive studies on risk factors for cerebral infarction in aPLA-positive patients remain sparse. In this retrospective single-center study, data from 9844 patients tested for aPLA between January 2017 and March 2023 were analyzed. A total of 647 aPLA-positive patients were included, with assessments of various factors including age, gender, hypertension, diabetes, dyslipidemia, smoking history, and cardiac disease. Propensity score matching was employed to create 2 matched groups of 202 patients each, comparing those with and without cerebral infarction. Logistic regression analyses were conducted to identify risk factors for cerebral infarction and progression of cerebrovascular stenosis. The mean age of the study cohort was 65.8 years, with 60% being male. LA was positive in 95.2% of the cases, aCL in 8.8%, and aβ2GPI in 5.3%. High-risk aPLA profiles were identified in 7.1% of the cases. In the cerebral infarction group, both smoking history and aCL positivity were significantly associated with an increased risk (OR = 1.543; 95% CI: 1.020-2.334; P = .040 and OR = 3.043; 95% CI: 1.426-6.491; P = .040, respectively). Male gender and posterior circulation involvement were significant risk factors for exacerbation of cerebrovascular stenosis (OR = 3.73; 95% CI: 1.16-16.69; P = .046 and OR = 5.41; 95% CI: 1.80-16.05; P = .002, respectively). Smoking history and aCL positivity are prominent risk factors for cerebral infarction in aPLA-positive patients, while male gender and involvement of the posterior circulation emerge as significant risk factors for the progression of cerebrovascular stenosis. Further comprehensive prospective studies are necessary to deepen understanding of aPLA-related cerebrovascular diseases., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in patients with antiphospholipid syndrome-associated venous thromboembolism (APS-VTE) remain uncertain. We aimed to evaluate efficacy and safety of DOACs in patients with APS-VTE., Methods: Using the Korean Health Insurance Review and Assessment Service database, we retrospectively identified all APS-VTE cases. We examined the VTE recurrence, arterial thrombosis, death and bleeding in patients who received DOACs compared with warfarin for therapeutic anticoagulation., Results: Of all the VTE cases (n = 84,916) detected between 2014 and 2018, patients with APS-VTE (n = 410) accounted for 0.48%. Most patients with APS-VTE (73%) were aged < 60 years. The recurrent VTE occurred in 8 of 209 patients (3.8%) who received DOACs and in 7 of 201 (3.5%) who received warfarin (relative risk [RR], 1.099; 95% confidence interval [CI], 0.41-2.98; P = 1.000). The arterial thrombosis (ATE) occurred in 8 of 209 patients (3.8%) who received DOAC and in 20 of 201 (10%) who received warfarin (RR, 0.385; 95% CI, 0.17-0.85; P = 0.024). The composite outcomes of VTE recurrence, ATE, or mortality were significantly lower in patients (9.1%) on DOAC than in those (16.3%) on warfarin (RR, 0.537; 95% CI, 0.32-0.91; P = 0.028). The bleeding outcome occurred in 7 of 209 (3.4%) patients in the DOACs group and 7 of 201 (3.5%) patients in the warfarin group (RR, 0.96; 95% CI, 0.34-2.69; P = 0.840)., Conclusion: In patients with APS-VTE, DOACs group showed comparable rates of recurrent VTE, bleeding, and deaths, but a significantly lower incidence of ATE and composite outcomes compared with the warfarin group in Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Patients with thrombotic antiphospholipid syndrome (APS) are at high risk for recurrent thrombosis, and indefinite anticoagulation is recommended. Patients with APS merit indefinite anticoagulation, and vitamin K antagonists (VKAs) have historically been the standard treatment. Direct oral anticoagulants (DOACs) present an appealing alternative to VKAs. Due to their pharmacokinetic and pharmacodynamic characteristics, DOACs offer advantages over VKAs, namely the lack of need for laboratory monitoring, the usage of a fixed dosage, and the absence of significant interaction with dietary components and drugs. The efficacy and safety of DOACs in patients with APS have been studied in four phase II/III clinical trials (three with rivaroxaban and one with apixaban). These studies showed DOACs' inferiority compared to VKAs in preventing recurrent thrombosis. Recurrence was significantly greater in patients with arterial thrombotic events and a triple positivity for antiphospholipid antibodies. No differences were observed in the incidence of venous thromboembolism between both groups. Major bleeding was similar in patients treated with DOACs or VKAs. Several observational studies have reported similar results. This review aims to analyse the existing evidence on the efficacy and safety of DOACs for secondary prevention in patients with APS.

Problem: To compare the clinical characteristics and pregnancy outcomes between patients with primary obstetric antiphospholipid syndrome (OAPS) and those with primary non-criteria obstetric antiphospholipid syndrome (NC-OAPS), and to identify the risk factors of adverse pregnancy outcomes in both groups., Methods: A retrospective single-center study was performed in a university hospital of western China, including 141 patients with OAPS and 865 patients with NC-OAPS. The clinical characteristics, pregnancy complications, and obstetric outcomes of the cohorts were collected from the hospital system and were compared by univariable analysis, and the independent risk factors for adverse pregnancy outcomes (APO) were investigated by logistic regression analysis in these two populations., Results: The OAPS patients had a significantly higher risk for stillbirths compared to the NC-OAPS patients, while the NC-OAPS group had a significantly higher risk for preterm birth and overall APO. Double aPL positivity, triple aPL positivity, and gestational hypertension were the independent risk factors for APO in OAPS patients, whereas two of the double aPL positivity subtypes, triple aPL positivity and placenta previa were independent risk factors for APO in NC-OAPS patients., Conclusion: This study identified different rates in different APOs among OAPS and NC-OAPS patients. Additionally, this study revealed different risk factors for the development of APO between the two populations. These findings indicated that OAPS and NC-OAPS are two distinct entities of the same disease, providing new insights into the individualized management for patients with OAPS and NC-OAPS., (© 2024 The Author(s). American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Catatrophic antiphospholipid syndrome (CAPS), a rare variant of antiphospholipid syndrome (APS), is associated with rapid multiorgan failure. While APS is associated with single medium-to-large blood vessel occlusions, CAPS is most often associated with several, concurrent vascular occlusions of small vessels, commonly of the kidneys, heart, skin and brain. We present a case of a 21-year-old female patient with a history of immune thrombocytopenia purpura and APS, who eventually developed concurrent cerebral venous sinus thrombosis, diffuse alveolar haemorrhage, renal thrombotic microangiopathy, and a necrotic, vasculitic wound on her forearm. Despite hospitalisation and treatment, her condition worsened and the patient eventually died after succumbing to suspected CAPS.

Antiphospholipid syndrome (APS) in children is a rare disease associated with significant morbidity and mortality. In comparison with APS in adults, pediatric APS has a more severe presentation with frequent recurrences of thrombotic events and a higher probability of life-threatening catastrophic APS. Nonthrombotic manifestations are also more common in the pediatric age group and can precede thrombosis. New classification criteria have been introduced recently and have not yet been assessed in pediatric patients with APS. In addition to anticoagulation drugs, other novel therapies have emerged including the use of B cell and complement inhibitors, especially in catastrophic APS. The purpose of this review is to provide a broad overview of aPL-related clinical manifestations in pediatric patients based on the analysis of published cohorts and data from the international pediatric APS registry. We also aim to illustrate APS in infants caused by transplacentally transferred maternal aPL, which is very rarely associated with acute thrombotic events in the perinatal period and more frequently with long-term neurodevelopmental abnormalities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Antiphospholipid syndrome (APS) is an autoimmune disease mainly affecting young individuals. Testing for antiphospholipid antibodies is recommended for young patients who are suspected to have APS. Yet, it is hard to differentiate APS from other acquired thrombophilia disorders in elderly-onset APS patients. This study aim to investigate the characteristics and prognosis of elderly-onset APS., Methods: This is an observational cohort study. Thrombotic APS patients who underwent follow-ups between 2009 and 2022 were included. Elderly-onset APS patients (onset age ≥60 years) were compared to non-elderly-onset APS patients (onset age <60 years) and matched cases of elderly non-APS patients (age ≥60 years with thrombosis)., Results: A total of 161 APS patients were included in this study, 45 (28.0%) were elderly-onset APS. Stroke (35.6% vs. 18.1%, p = .018) was more common at disease onset in elderly-onset APS patients. Compared to non-elderly-onset patients, elderly-onset APS patients were associated with a higher number of cardiovascular risk factors. Elderly-onset APS patients showed significantly lower positive rate (51.1% vs. 71.6%, p = .014) and ratios [1.24 (1.01-1.38) vs. 1.37 (1.16-1.77), p = .004] of lupus anticoagulant. Elderly-onset APS patients had a significantly higher 10-years cumulative all-cause mortality ( p < .001) and APS-related mortality than non-elderly-onset patients ( p = .002) and elderly non-APS patients ( p = .040)., Conclusions: Elderly-onset APS patients have unique disease characteristics with higher 10-years cumulative all-cause mortality and APS-related mortality. Early recognition and control of comorbidities may reduce the recurrence of thrombosis and mortality in elderly-onset APS patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Severe thrombotic antiphospholipid syndrome (APS) frequently affects the kidney, heart, and central nervous system. The precise frequency, clinical picture, differential diagnoses, and outcome of APS-related hematological involvement are lacking, especially in patients requiring ICU admission. This study aimed to describe the hematological manifestations associated with critically ill thrombotic APS patients and catastrophic antiphospholipid syndrome., Methods: This French, national, multicenter, retrospective study, conducted, from January 2000 to September 2018, included all APS patients admitted to 24 participating centers' ICUs with any new thrombotic manifestation. The prevalence of hematological manifestations and their associated outcomes were studied., Results: One hundred and thirty-four patients, female 72%, median [IQR] age 45 [34-56] years, with 152 episodes were included. Anemia was present in 95% of episodes and thrombocytopenia in 93%. The lowest values for hemoglobin and platelets were 7.1 [6.3-8.8] g/dL and 38 [21-60] g/L, respectively. The lowest platelet count below 20 g/L was significantly associated with a higher in-ICU mortality rate (50%, p < 0.0001). A thrombotic microangiopathy syndrome (TMA) syndrome was seen in 16 patients (12%) and was associated with higher in-hospital mortality (p = 0.05). Median ADAMTS-13 levels were 44% [27-74]. Anti-ADAMTS13 antibodies were tested in 11 patients and found negative in all. A suspicion of heparin-induced thrombocytopenia (HIT) was raised in 66 patients but only four patients were classified as definite HIT. Disseminated intravascular coagulation (DIC) was seen in 51% of patients., Conclusion: Thrombocytopenia is very frequent in severe APS patients and may be related to TMA, HIT, or DIC. Deciphering the mechanisms of thrombocytopenia is decisive in CAPS patients. Key Points • Thrombocytopenia is the hallmark laboratory finding in CAPS. • A complete thrombotic microangiopathy pattern is infrequent in CAPS patients. • Alternate diagnoses of CAPS, especially heparin-induced thrombocytopenia, need to be adequately investigated., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: To assess the impact of concomitant systemic lupus erythematosus (SLE) on the clinicopathological manifestations of thrombotic antiphospholipid syndrome (APS)., Methods: This single-centre, retrospective study compared clinical and antiphospholipid antibody (aPL) data from 118 patients, 58 with SLE-associated APS (SLE-APS), and 60 with primary APS., Results: Median follow-up was 13.9 (IQR 7.7-19.3) and 8.6 years (3.5-10.6) for the SLE-APS cohort and PAPS cohort, respectively. Age at diagnosis of APS was lower in the SLE-APS cohort (mean 35.9 vs PAPS: 46.7 years; p < 0.05). Distribution of aPL subtypes was similar across cohorts. 198 thrombotic events were identified overall (index plus recurrent), with venous thromboembolism (VTE) and arterial thrombosis each occurring in just over half of patients in both cohorts. Microvascular thrombosis (12.1% vs 0%), and a mixed (any combination of venous, arterial and microvascular) thrombotic phenotype (19.0% vs 6.7%, p = 0.05) were more prevalent in SLE-APS patients. Recurrent thrombosis incidence rates (∼0.5 events/10-patient years), and Kaplan-Meier recurrence-free survival after index thrombosis, were similar. In the PAPS cohort, only: (i) triple-aPL-positivity was associated with a significantly higher recurrent thrombosis event rate (incidence rate ratio 2.22, p = 0.03) and lower recurrence-free survival after first thrombosis (log-rank test p = 0.01); (ii) lupus anticoagulant (LA)-positivity was associated with higher prevalance of arterial thrombosis (RR 2.69, p = 0.01), and lower prevlance of VTE (RR 0.48, p < 0.001), versus LA-negativity., Conclusion: Concomitant SLE does not appear to modify long-term recurrent thrombosis risk, or aPL phenotypes, in patients with APS. Triple-aPL-positivity and LA-positive status may have less influence on thrombotic outcomes in patients with SLE-APS compared to PAPS., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HC reports, outside the submitted work, institutional research support and support to attend scientific meetings from Bayer Healthcare; Roche Advisory Board; Consultancy fees from UCB Biopharma and Speaker fees from Technoclone paid to University College London Hospitals Charity. ME reports consultancy fees from Alexion Pharmaceutical. PM, MP, LT, JR, IT and DI have nothing to disclose.

Antiphospholipid syndrome (APS) is an autoimmune disorder that presents with hypercoagulability and results in a lab artifact of prolonged PTT. The most severe form is catastrophic antiphospholipid antibody syndrome (CAPS), which manifests as rapidly progressing thromboses in multiple organ systems leading to multi-organ ischemia. The mainstay management CAPS is anticoagulation and systemic corticosteroids. Antifibrinolytic agents have previously been thought to be relatively contraindicated in CAPS due to the pro-thrombotic nature of the disease; the complex coagulation profile of CAPS can make it difficult to assess the risks and benefits of antifibrinolytic therapy. Also, should a patient with CAPS require cardiopulmonary bypass (CPB) for surgery, it poses a unique challenge in providing appropriate anticoagulation in the setting of prolonged ACT. We present a case of a 32-year-old postpartum female with CAPS requiring heart transplant who safely received intraoperative antifibrinolytic therapy and was successfully anticoagulated during CPB after perioperative plasmapheresis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chorea is a hyperkinetic movement disorder associated with various underlyingconditions, including autoimmune diseases such as antiphospholipid syndrome (APS). APS can manifest with a wide range of neurological symptoms, including chorea. We present a case of a 77-year-old man with subacute generalized chorea secondary to primary APS. Notably, the patient exhibited a left patellar crossed-reflex, a phenomenon rarely documented in chorea cases, the pathophysiology of which has not yet been elucidated. In summary, this case challenges the traditional demographics of antiphospholipid syndrome (APS) by suggesting a potential link between APS and late-age patients. It emphasizes the importance of considering APS in late-onset chorea cases., (© 2024. The Author(s).)

Persistence of serum antiphospholipid antibodies (aPL) is associated with a high thrombotic risk, both arterial and venous, and with pregnancy complications. Due to the potential morbidity and mortality associated with the presence of aPL, identifying and recognizing risk factors for the development of aPL and thrombosis in aPL carriers may help to prevent and reduce the burden of disease. Multiple elements are involved in the pathomechanism of aPL development and aPL-related thrombosis such as genetics, malignancy, and infections. This review will address the role of both well-known risk factors and their evolution, and of emerging risk factors, including COVID-19, in the development of aPL and thrombosis in aPL carriers., Competing Interests: None declared., (Thieme. All rights reserved.)

In addition to the respiratory symptoms associated with COVID-19, the disease has consistently been linked to many autoimmune diseases such as systemic lupus erythematous and antiphospholipid syndrome (APS). APS in particular was of paramount significance due to its devastating clinical sequela. In fact, the hypercoagulable state seen in patients with acute COVID-19 and the critical role of anticoagulant treatment in affected individuals shed light on the possible relatedness between APS and COVID-19. Moreover, the role of autoimmunity in the assumed association is not less important especially with the accumulated data available regarding the autoimmunity-triggering effect of SARS-CoV-2 infection. This is furtherly strengthened at the time patients with COVID-19 manifested antiphospholipid antibodies of different types following infection. Additionally, the severe form of the APS spectrum, catastrophic APS (CAPS), was shown to have overlapping characteristics with severe COVID-19 such as cytokine storm and multi-organ failure. Interestingly, COVID vaccine-induced autoimmune phenomena described in the medical literature have pointed to an association with APS. Whether the antiphospholipid antibodies were present or de novo, COVID vaccine-induced vascular thrombosis in certain individuals necessitates further investigations regarding the possible mechanisms involved. In our current paper, we aimed to focus on the associations mentioned, their implications, importance, and consequences., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Anesthesia for cardiac surgical patients with antiphospholipid antibody syndrome (APLS) presents challenges with monitoring anticoagulation during cardiopulmonary bypass. Additionally, this condition is associated with other autoimmune diseases and comorbidities that need to be considered in caring for these patients, and there is minimal evidence for specific strategies during cardiac surgery. Separately, Jehovah's Witness (JW) patients typically do not consent to receiving blood products, presenting an additional challenge for resuscitation during cardiac surgery and especially in the context of APLS. We present our approach to the anesthetic management of a JW patient with systemic lupus erythematosus (SLE) complicated by APLS, thrombocytopenia, and renal failure with history of renal transplant who presented for coronary artery bypass surgery. Management strategies we recommend include administration of antifibrinolytics after heparinization to mitigate bleeding risk and interdisciplinary management with the perfusion, intensive care, surgical, and nephrology teams., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Greco: none. Dr Varelmann: receiving royalties from UpToDate (Wolters Kluwer),consulting fees from Edwards (stopped 2019), and from EnCare (ended 2021). Dr Patel: none.

Introduction: Despite thromboprophylaxis, women with antiphospholipid syndrome (APS) face high-risk pregnancies due to proinflammatory and prothrombotic states. This highlights the need for new monitoring and prognostic tools. Recent insights into the pathophysiological role of neutrophil activation and extracellular trap (NET) formation in this syndrome led to the exploration of plasma cell-free DNA (cfDNA), a derivative of NETosis, as a promising biomarker., Materials and Methods: cfDNA was isolated and quantified from plasma samples of healthy pregnant women (control group, HC) and women with APS (APS group). We assessed the physiological variability of cfDNA across the three trimesters in HC. Levels of cfDNA were compared between APS and HC by gestational trimester. ROC curve analysis was performed to evaluate the efficacy of cfDNA levels for classifying APS patients. Furthermore, cfDNA levels in pregnant women with APS with obstetric complications were compared to those from uncomplicated pregnancies., Results: Among HC, cfDNA significantly increased in the third trimester compared to the first and second. Elevated cfDNA levels in APS compared to HC were observed in the first and second trimesters. First-trimester cfDNA levels demonstrated the highest classification ability to discriminate between APS and HC patients (AUC: 0.906). Among APS, those with complicated pregnancies (fetal growth restriction, preeclampsia, placenta accreta) exhibited significantly elevated cfDNA levels in the second trimester., Conclusions: Elevated levels of cfDNA in pregnant women with APS, particularly among those with obstetric complications, supports further investigation into the potential of cfDNA as a valuable tool in the obstetric management of women with APS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Antiphospholipid syndrome (APS) is a systemic autoimmune condition that predisposes patients to venous thromboembolism (VTE). Although many studies have explored risk factors for VTE after joint reconstructive procedures, the impact of APS is still unclear., Materials and Methods: A retrospective cohort study was conducted using TriNetX, a health care database that includes 442,494 patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). Ninety-day postoperative complications and 1- and 2-year surgical complications were compared between patients with and without preexisting APS. Patients underwent propensity score matching in a 1:1 ratio based on relevant comorbidities., Results: Patients undergoing THA or TKA with APS, compared with those without, had higher rates of deep venous thrombosis (hip: 9.2% vs 6.0%, odds ratio, 1.589, P =.022; knee: 10.5% vs 4.1%, odds ratio, 2.763, P <.001), pulmonary embolism (hip: 6.9% vs 3.6%, odds ratio, 1.992, P =.005; knee: 8.4% vs 3.0%, odds ratio, 2.989, P <.001), and anemia (hip: 24.8% vs 18.6%, odds ratio, 1.447, P =.004; knee: 18.5% vs 13.9%, odds ratio, 1.406, P =.007). Patients undergoing THA with APS also had higher rates of urinary tract infection (5.0% vs 2.8%, odds ratio, 1.842, P =.029) and pneumonia (3.7% vs 1.8%, odds ratio, 2.119, P =.025). APS did not impact rates of surgical complications or revision surgery., Conclusion: Overall, APS heightens patients' risk for complications after THA and TKA. Specific anticoagulation protocols and preoperative risk stratification should be implemented to reduce the risk of adverse events. [ Orthopedics . 2024;47(5):301-307.].

Objectives: Cerebral venous sinus thrombosis (CVST) is a rare but serious manifestation of venous thrombosis in patients with antiphospholipid syndrome (APS). This study investigated the risk factors, clinical characteristics and prognosis of CVST in APS patients., Methods: This retrospective cohort study included all thrombotic APS (tAPS) patients from Peking Union Medical College Hospital (PUMCH) from April 2005 to August 2023. Demographic characteristics, laboratory data and thrombotic risk factors were compared between tAPS-CVST group and tAPS-non-CVST group. Kaplan-Meier survival analysis was utilized to compare the recanalization rate and the recurrence rate., Results: A total of 453 APS patients were enrolled, and 40 (8.8%) APS patients were with CVST. The median age of the APS-CVST patients was 27 (21.25, 32.75) years, and 72.5% were females. In 50% of these patients, CVST was the initial symptom of APS, with headache being the most prevalent clinical symptom (95%). Involvement of more than two venous sinuses were observed in 79.5% of patients, with the transverse sinus (79.5%) and sigmoid sinus (74.4%) being the most commonly affected sites. Oral contraceptives, intracranial infections and malignancy were identified as risk factors of APS-CVST. There were no statistically significant differences in baseline characteristics or the distribution of antiphospholipid antibodies profiles between the two groups. After a median follow-up of 24 (12, 52) months, 21 patients (52.5%) experienced recanalization, and 13 patients (32.5%) had a thrombotic recurrence. Survival analysis indicated that adequate anticoagulant therapy significantly contributed to recanalization (HR 6.27, 95% CI 2.616-15.02, P = 0.003), while continuous anticoagulant therapy was highly effective in reducing the recurrence of thrombotic events (HR 0.14, 95% CI 0.0447-0.4328, P = 0.0007)., Conclusion: CVST should be considered in APS patients who experience sudden onset headaches, particularly those with thrombotic risk factors, such as the use of oral contraceptives, intracranial infections and malignancy. Continuous and adequate anticoagulant therapy is pivotal and beneficial for achieving recanalization and prevention of recurrence. Key Points • The prevalence of CVST in patients with APS may be underestimated. • APS-CVST is associated with special risk factors, including pregnancy, intracranial infection, oral contraceptives and tumors. • Long-term and adequate anticoagulation therapy can increase the vascular recanalization rate and reduce thrombosis recurrence., Competing Interests: Declarations. Conflicting interests: All authors declare that there are no conflicts of interest., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Importance: Antiphospholipid syndrome in neonates and children is a rare, but in some cases life-threatening condition with arterial and/or venous thrombosis and/or non-thrombotic neurological, skin, ophthalmological and other manifestations., Observations: This review highlights the available information about the features of pediatric APS, including the rare catastrophic form, the differences between pediatric and adult APS, and the role of genetic thrombophilia in APS manifestation., Conclusions and Relevance: The clinical manifestations and treatment options for APS in children may differ from those in adults, and prescribing therapy can be challenging due to the unique clinical and morphological characteristics of the pediatric patient. Pediatric APS may be a predictor of the development of certain autoimmune diseases and classic manifestations of APS in adulthood, therefore, a revision of the existing criteria for the diagnosis and treatment of APS in children is necessary.

Introduction: Systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS) represents a challenging SLE endotype whose molecular basis remains unknown., Methods: We analysed whole-blood RNA-sequencing data from 299 patients with SLE (108 SLE-antiphospholipid antibodies (aPL)-positive, including 67 SLE-APS; 191 SLE-aPL-negative) and 72 matched healthy controls (HC). Pathway enrichment analysis, unsupervised weighted gene coexpression network analysis and machine learning were applied to distinguish disease endotypes., Results: Patients with SLE-APS demonstrated upregulated type I and II interferon (IFN) pathways compared with HC. Using a 100-gene random forests model, we achieved a cross-validated accuracy of 75.6% in distinguishing these two states. Additionally, the comparison between SLE-APS and SLE-aPL-negative revealed 227 differentially expressed genes, indicating downregulation of IFN-α and IFN-γ signatures, coupled with dysregulation of the complement cascade, B-cell activation and neutrophil degranulation. Unsupervised analysis of SLE transcriptome identified 21 gene modules, with SLE-APS strongly linked to upregulation of the 'neutrophilic/myeloid' module. Within SLE-APS, venous thromboses positively correlated with 'neutrophilic/myeloid' and 'B cell' modules, while arterial thromboses were associated with dysregulation of 'DNA damage response (DDR)' and 'metabolism' modules. Anticardiolipin and anti-β2GPI positivity-irrespective of APS status-were associated with the 'neutrophilic/myeloid' and 'protein-binding' module, respectively., Conclusions: There is a hierarchical upregulation and-likely-dependence on IFN in SLE with the highest IFN signature observed in SLE-aPL-negative patients. Venous thrombotic events are associated with neutrophils and B cells while arterial events with DDR and impaired metabolism. This may account for their differential requirements for anticoagulation and provide rationale for the potential use of mTOR inhibitors such as sirolimus and the direct fIIa inhibitor dabigatran in SLE-APS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Competing Interests: Conflict of interest: None declared.

Rationale: Adrenal infarction (AI) is a rare type of adrenal damage, which is relatively common in systemic lupus erythematosus, antiphospholipid antibody syndrome (APS) and pregnancy. The diagnosis of AI is mainly by computed tomography (CT) and magnetic resonance imaging, but is easily confused with other adrenal disease. Hence, this report details a condition of AI with systemic lupus erythematosus, APS and made a differential diagnosis from imaging., Patient Concerns: We report a case of a 55-year-old woman with pain in her fossa axillaries and inguinal regions. Then CT scan disclosed bilateral adrenal diseases, and the patient was diagnosed with systemic lupus erythematosus, APS and AI after additional autoimmune examinations., Diagnoses: The patient was diagnosed as systemic lupus erythematosus with lupus nephritis, hematological damage and oromeningitis, APS, AI and secondary blood coagulation disorders., Interventions: The patient was treated with methylprednisolone, hydroxychloroquine and low molecular heparin., Outcomes: The patient relieves and remains well 1 year after treatment., Lessons Subsections: AI can be divided hemorrhagic and non-hemorrhagic, with bilateral lesions more common. In our case, the AI was bilateral, partially involved and non-hemorrhagic, and the "cutoff sign" was first put forward in CT, which might assist the diagnosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Antiphospholipid syndrome (APS) is the most frequent acquired thrombophilia of autoimmune basis. Pregnancy complications of APS may include recurrent miscarriage, and placental dysfunction presenting as fetal death, prematurity, intrauterine growth restriction and preeclampsia. For the management of obstetric APS, a coordinated medical-obstetric management is essential, and this should start for a preconceptional visit in order to estimate the individual risk for complications, adjust therapies and establish the indications for preconceptional and first-trimester therapy. The basis of APS therapy during pregnancy is low-dose aspirin, combined in certain clinical scenarios with low-molecular weight heparin. Induction of delivery should not be routinely indicated in the absence of maternal and/or fetal complications. Postpartum management should be warranted., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

The catastrophic antiphospholipid syndrome (CAPS) is a rare life-threatening clinical condition that represents the most severe clinical presentation of the antiphospholipid syndrome (APS). It was first described in 1992 in a group of patients that presented with multiorgan involvement and microangiopathic features of APS. Most of the current knowledge of CAPS comes from the analysis of all cases collected at the "CAPS Registry" that was created in 2000 to perform studies on this condition. Most cases are triggered by a prothrombotic situation that leads to a multiorgan thrombosis and a cytokine storm. The analysis of cases included in the "CAPS Registry" has shown that the triple therapy with anticoagulation, glucocorticoids, and plasma exchange and/or intravenous immunoglobulins is associated to a better prognosis of CAPS. The improvement of the knowledge allowed a decrease from the 50% mortality rate reported in the first series to 25-30% in the most recent publications., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)