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Recurrent pregnancy loss (RPL) affects approximately 5% of couples. Although RPL definitions vary across professional societies, an evaluation after a second clinically recognized first-trimester pregnancy loss is recommended. Good quality evidence links parental chromosomal rearrangements, uterine anomalies, and antiphospholipid syndrome (APS) to RPL. In contrast, the relationship between RPL and other endocrine, hematologic, and immunologic disorders or environmental exposures is less clear. Anticoagulant therapy and low-dose aspirin are recommended for patients with RPL who have also been diagnosed with APS. Vaginal progesterone supplementation may be considered in patients experiencing vaginal bleeding during the first trimester. Surgical correction may be considered for patients with RPL in whom a uterine anomaly is identified. Evaluation and management of additional comorbidities should be guided by the patient's history rather than solely based on the diagnosis of RPL, with the goal of improving overall health to reduce complications in the event of pregnancy. Most people with RPL, including those without identifiable risk factors, are expected to achieve a live birth within 5 years from the initial evaluation. Nevertheless, clinicians should be sensitive to the psychological needs of individuals with this condition and provide compassionate and supportive care across all stages., Competing Interests: Financial Disclosure Stephanie T. Ros disclosed receiving payment from UpToDate for a chapter about Zika in pregnancy. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

This document is an editorial celebrating the 50th anniversary of Seminars in Thrombosis and Hemostasis (STH), a medical journal that first published in 1974. The editorial discusses the various celebratory issues that have been published over the years, which contain historical content related to the fields of thrombosis and hemostasis. The document also mentions the republishing of highly cited and downloaded papers from STH, along with accompanying commentaries from experts in the respective fields. Additionally, the document provides a list of the 50 most highly downloaded papers from STH between 2014 and 2023. [Extracted from the article]

Background: Diagnosing Antiphospholipid Syndrome (APS) relies heavily on laboratory findings, particularly the detection of specific antibodies like lupus anticoagulant (LA), IgG and/or IgM anti-cardiolipin (aCL), and IgG and/or IgM anti-β2 glycoprotein 1 (aB2GP1). Although ELISA is widely used in the US for this purpose, standardization between different assay methodologies remains challenging, leading to significant variability across laboratories. Particle-based multi-analyte technology (PMAT) offers a streamlined one-step detection for all six antiphospholipid (aPL) autoantibodies, covering aCL and aB2GP1 of IgA, IgG, and IgM isotypes., Methods: In this study involving 224 subjects, including 34 clinically diagnosed with APS, alongside 160 non-APS patients and 30 healthy donors, PMAT's performance was evaluated against commercial ELISA in detecting aPL antibodies., Results: At the manufacturer's suggested cutoff, PMAT exhibited sensitivity comparable to ELISA, albeit with a low to moderate decrease in specificity for certain antibodies. With anti-CL IgM alone, PMAT displayed a 17.7% decrease in sensitivity, accompanied by a corresponding 31.1% increase in specificity compared to ELISA. However, applying a stricter cutoff (88-90% specificity), IgA and IgM antibodies yielded 5.9-17.6% higher sensitivities with PMAT, and IgG antibodies displayed similar sensitivity., Conclusions: In this study cohort, PMAT demonstrated higher or comparable sensitivity to that of commercial ELISA for all six aPL antibodies at a specificity cutoff near 90%. Notably, PMAT demonstrated superior sensitivity and specificity overall in detecting IgA aCL and aB2GP1 antibodies. This study highlights the potential of automated PMAT for detecting aPL antibodies in APS evaluation., 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 B.V. All rights reserved.)

Objective: This paper presents an analysis of the pregnancy trajectory and therapeutic regimen documentation of a primigravida with APSN. It aims at communicating the therapeutic approach and preventive measures for APSN in pregnancy., Case Presentation: This paper reports the trajectory and therapeutic regimen documentation of a primigravida with APSN. The APSN was discovered in a primigravida woman aged 26 years at 11 weeks of gestation. The initial therapy regimen consists of daily administration of prednisone 10 mg, hydroxychloroquine 200 mg, dapparin 5000 IU, and aspirin 50 mg. At a gestational age of 20 + 3 weeks, the dosage of dapparin was modified to 5000 IU/other day, along with a significant rise in urinary protein level seen at 30 + 3 weeks of gestational age. The initial dosage of dapanin sodium was renewed. The patient delivered at 38 + 3 weeks of gestation without other complications., Conclusion: It is imperative to acknowledge that altering the dosage and administration of medication should not be done haphazardly during pregnancy., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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

Background: Antiphospholipid syndrome (APS) can occur primarily (PAPS) or secondary to another autoimmune disease (SAPS), most commonly systemic lupus erythematosus (SLE). Recently, we reported that subclinical brain involvement was highly prevalent in patients with autoimmune diseases, including SLE. We aimed to investigate whether patients with SLE, PAPS or SAPS and cardiac symptoms showed differences in cardiac/brain involvement based on combined brain-heart magnetic resonance imaging (MRI)., Methods: We prospectively recruited 15 patients with SAPS (86 % with SLE) and 3 patients with PAPS and compared their MRI findings to those of 13 patients with SLE from our previous publication. All patients underwent routine cardiovascular/neurological examination and standard echocardiography., Results: No patients had abnormalities in routine clinical workup/echocardiography. The vast majority had white matter hyperintensities (WMHs) and all had evidence of myocardial fibrosis and/or inflammation. Patients with SAPS had a lower median WMH number [1.00 (1.00, 2.00)] than those with PAPS [3.00 (2.50, 3.00)] or SLE [2.00 (2.00, 3.00)] (p = 0.010). Subcortical and deep WM were highly prevalent. Periventricular WMHs were more frequent in patients with SLE [6 (46.2 %)] or PAPS [2 (66.7 %)] (p = 0.023). Higher lesion burdens (1 WMH vs. 2 WMHs vs. ≥ WMHs) were associated with the presence of cardiac fibrosis [3 (33.3 %) vs. 10 (83.3) vs. 7 (77.8), p = 0.039] and affected the deep and periventricular WM (p < 0.001 for both)., Conclusion: In patients with PAPS, SAPS or SLE, cardiac symptoms and normal routine workup, combined brain-heart MRI identified abnormalities in both organs in the majority of patients. Combined brain-heart MRI offers excellent diagnostic value, but its incorporation into routine clinical practice should be further investigated. Clinical relevance statement Combined brain-heart magnetic resonance imaging in antiphospholipid syndrome may help to assess the presence of abnormalities in both organs., 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 B.V. All rights reserved.)

This document is a list of articles published in the journal Seminars in Thrombosis and Hemostasis. The articles cover a wide range of topics related to platelets, coagulation, and thrombosis. Some of the topics include the role of platelets in cancer, the measurement of microparticles, risk factors for venous thromboembolism, and the use of statins in COVID-19 patients. The articles provide valuable information for researchers and healthcare professionals interested in these areas of study. [Extracted from the article]

In antiphospholipid syndrome (APS), the risk of clinical manifestations increases with higher titers of antiphospholipid antibodies (aPL). Despite the adoption of aPL titers in the classification approach to aPL-positive subjects, the value of longitudinal monitoring of those titers in the follow-up is still debated, being well studied only in systemic lupus erythematosus (SLE). The literature suggests that the rate of aPL positivity decreases during follow-up in primary APS, estimating that seroconversion occurs in between 8.9 and 59% of patients over time. Negativisation of aPL occurs more frequently in asymptomatic aPL carriers than in patients with full-blown APS as well as in subjects with single aPL positivity or low aPL antibody titers. In patients with SLE, aPL typically behave fluctuating from positive to negative and back again in the course of follow-up. The few studies assessing the longitudinal course of aPL positivity with no associated systemic connective tissue disease reported a progressive decrement of aPL titers over time, in particular of antibodies against β2 glycoprotein I (antiβ2GPI) and cardiolipin (aCL) of IgG isotype. After a thrombotic event, aPL titers tend to decrease, as emerged from cohorts of both primary and secondary APS. Hydroxychloroquine has been identified as the most effective pharmacological agent to reduce aPL titers, with multiple studies demonstrating a parallel reduction in thrombosis rate. This review addresses available evidence on the significance of aPL titer fluctuation from clinical, therapeutic and pathogenic perspectives., 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 B.V. All rights reserved.)

Background and Aims: Several non-criteria (NC) anti-phospholipid antibodies (APLA) have been proposed as candidates for antiphospholipid antibody syndrome (APS) diagnosis. The objectives of this study were 1) to determine the association of five different NC-APLA with positivity for Lupus anti-coagulant (LAC) and the criteria antibodies anti-cardiolipin (aCL) and anti-beta glycoprotein (aB2GPI), and 2) to assess the ability of NC-APLA to predict LAC presence and clinical APS diagnoses., Material and Methods: Results from 486 patients tested for LAC and APLA were retrieved. Patients were grouped according to LAC and serology positivity into three groups: Single-positives (SP) for LAC, aCL or aB2GPI; Double-positives for aCL and aB2GPI; Triple-positives (TP) for LAC, aCL and aB2GPI. NC-ALPA titers were compared between LAC-positive and negative and APS and non-APS patients., Results: Forty-two of 486 patients were LAC-positive and 28 were diagnosed with APS. All criteria and NC-APLA titers were significantly higher in TP than SP patients. ROC analyses based on LAC status showed highest area under the curve (AUC, 95% CI) for aPS/PT IgG (0.75, 0.65-0.85) and aPS/PT IgM (0.73, 0.63-0.82). Based on APS diagnosis, aPS/PT IgM achieved highest AUC (0.87; 0.79-0.95)., Conclusion: Anti-phosphatidyl-serine/prothrombin (aPS/PT) antibodies are superior predictors of LAC presence and APS diagnoses., 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. Published by Elsevier B.V.)

The antiphospholipid syndrome (APS) is an autoimmune and prothrombotic condition defined by the association of thrombotic events and/or obstetrical complications and the persistence of antiphospholipid antibodies (aPL) over time. Among the new criteria recently included in the 2023 ACR/EULAR classification criteria for APS, thrombocytopenia is one of the most frequent. The occurrence of thrombocytopenia in aPL/APS patients is important to consider because it could predict APS-related clinical events with a 3-fold increased risk for thrombotic events or obstetrical morbidity or all-cause deaths. A debate on the need or not of anticoagulation and/or antiaggregation in APS patients and aPL carriers with thrombocytopenia took place on the 7th edition of the International Congress on Controversies in Rheumatology and Autoimmunity (CORA), that was organized in Turin, Italy, on March 18th, 2023, and this review summarizes the main arguments that were discussed in this session., 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 © 2023 Elsevier B.V. All rights reserved.)

Long-term vitamin K antagonist (VKA) anticoagulation is the cornerstone of the management of subjects with thrombotic antiphospholipid syndrome (APS). Recent investigations have opened up new discussion points regarding the potential for stopping anticoagulant medication in patients with a history of thrombotic APS who no longer have detectable aPL (the so called aPL negativization). Despite the lack of unanimous agreement, some experts agreed on defining aPL negativization as the presence of two negative determinations, 1 year apart. What to do in order to optimize the management of these subjects with thrombotic APS when aPL turn negative is still a matter of debate. In this review, we aim to summarize the main evidence highlighting the magnitude of aPL negativizing among patients with APS and the features to keep in mind when considering (or not) stopping anticoagulation., 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 © 2023. Published by Elsevier B.V.)

Cardiovascular diseases, among which includes coronary artery disease, represent one of the most important causes of mortality and morbidity worldwide. Research aimed at determining the risk factors involved recognizes a group of "traditional" risk factors, but also more recent studies identified over 100 "novel" ones which may have a role in the disease. Among the latter is the thrombophilia profile of a patient, a pathology well-established for its involvement in venous thromboembolism, but with less studied implications in arterial thrombosis. This paper reviews the literature, explaining the pathophysiology of the thrombophilia causes associated most with coronary thrombosis events. Results of several studies on the subject, including a meta-analysis with over 60,000 subjects, determined the significant involvement of factor V Leiden, prothrombin G20210A mutation, plasminogen activator inhibitor–1 and antiphospholipid syndrome in the development of coronary artery disease. The mechanisms involved are currently at different stages of research, with some already established and used as therapeutic targets. [ABSTRACT FROM AUTHOR]

The latest issue of Seminars in Thrombosis and Hemostasis (STH) is a compilation of articles covering various topics related to thrombosis and bleeding. It includes reviews on neonates with intrauterine growth restriction, pediatric presentations of the antiphospholipid syndrome, genetic variations in tissue factor-dependent disease, heterozygous factor XIII deficiency, and the use of global hemostasis assays in patients with myeloproliferative neoplasms. The document also features reviews on the role of CD36 in platelet activation, laser-induced blood coagulation in surgery, detecting blood clots in ECMO circuits, post-COVID venous thrombosis, and the effects of SARS-CoV-2 spike protein variants on platelets. Commentaries on various topics and the republishing of historical papers are also included. [Extracted from the article]

Thrombosis in antiphospholipid syndrome (APS) involves in most cases the venous circulation. Why in some patients thrombotic APS affects the arterial circulation and in particular cerebral circulation is unknown. In previous studies, both patient characteristics and antiphospholipid antibody types and titers have been associated with arterial thrombosis. Aim of this study was to compare the clinical characteristics and laboratory findings of venous and arterial thrombotic APS from a large series of patients. Data were retrieved from the Start 2 antiphospholipid, a multicenter prospective register of long-term collected data from Thrombosis Centers in Italy. Of 167 patients with thrombotic APS, 114 (68 %) had a venous and 53 (32 %) had an arterial event as first clinical manifestation. Several clinical characteristics and risk factors were different among groups in univariate analysis. Using logistic regression analysis, reduced creatinine clearance and hyperlipidemia were independent variable for the occurrence of arterial APS. Notably, no difference in antiphospholipid antibody profiles and aβ2-Glycoprotein I levels were found between groups. A higher adjusted global antiphospholipid syndrome score (aGAPSS) was found in arterial group indicating a possible high recurrence rate in arterial APS. These data have pathophysiological and clinical implication since associated conditions might predispose patients to arterial rather than venous events and call to a close monitoring and treatment of arterial APS due to their increased tendency to recurrence. [ABSTRACT FROM AUTHOR]

This article aims to evaluate the magnitude of adverse pregnancy outcomes (APOs) risks associated with different antiphospholipid antibody (aPL) profiles in women with systemic lupus erythematosus (SLE). Multiple databases were investigated to identify articles that explored the relationship between aPLs and APOs in SLE patients. A random effects model was used for calculating pooled odds ratios (OR). Stata version 15.0 was utilized to conduct the meta-analysis. There were 5234 patients involved in 30 studies. Overall aPL was linked to an increased incidence of any kind of APOs, fetal loss, and preterm birth. Any kind of APOs and preterm delivery were more common in patients with lupus anticoagulant (LA) positive. Anticardiolipin antibody (aCL) was associated with an increased risk of any kind of APOs and fetal loss. The association between aCL-IgM and fetal loss was also significant. Patients with anti-beta2-glycoprotein1 antibody (antiβ2GP1) positivity had an increased risk of fetal loss. Both LA and aCL were risk factors of APOs in patients with SLE. Not only ACL, particularly aCL-IgM, but antiβ2GP1 were associated with an increased risk of fetal loss, while LA appeared to indicate the risk of preterm birth. PROSPERO (CRD42023388122). [ABSTRACT FROM AUTHOR]

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare entity characterized by the presence of lupus anticoagulant (LA) and prothrombin (factor II) deficiency. It may cause severe bleeding contrary to classical antiphospholipid syndrome. Here, we report a case of LAHPS presenting with a hemorrhagic ovarian cyst in a 17-year-old girl with systemic lupus erythematosus (SLE) nephritis. She had been followed up for 8 years. Her first manifestation of SLE was prolonged gingival bleeding after tooth extraction at 9 years of age. During the follow-up period, she had neither severe bleeding nor thrombotic complications despite a positive LA and a prolonged activated partial thromboplastin time (aPTT). At this visit, the patient presented with colicky abdominal pain, a hemorrhagic ovarian cyst, a prolonged prothrombin time, a prolonged aPTT, a low factor II level, and a positive LA, leading to the diagnosis of LAHPS. While a hemorrhagic ovarian cyst resolved completely in 3 months, she received oral pill, transfusions of red blood cells and plasma, and intravenous cyclophosphamide pulse therapy in combination with glucocorticoids due to persistent menorrhagia, anemia, prolonged aPTT, and lupus flaring. Thus, LAHPS needs to be considered in SLE patients with positive LA and prolonged aPTT. [ABSTRACT FROM AUTHOR]

Objectives: We aim to independently assess the validity of the damage index for antiphospholipid syndrome (DIAPS) in thrombotic antiphospholipid syndrome (APS) patients by exploring the prevalence and risk factors of organ damage and evaluating its impact on health-related quality of life (HR-QoL). Methods: Cross-sectional study including all thrombotic APS patients (Sydney criteria) attending a Portuguese tertiary centre. Damage was assessed using the DIAPS, and HR-QoL using the 3- and 5-level EuroQol HR-QoL (EQ-D5-3L and 5L), and Visual Analogue Scale (VAS) applied via a phone questionnaire. Spearman's correlation between DIAPS and the HR-QoL scales was performed. Risk factors for damage accrual and HR-QoL impairment were explored using univariate and multivariate logistic regression. Results: Among the 108 patients (female, 65.7%; white, 90.7%; primary APS, 75.9%; median disease duration, 6 years), damage (DIAPS≥1) developed in 48.2% of patients (mean ± SD DIAPS, 3.08 ± 1.83). DIAPS's neuropsychiatric domain was the most affected (24.2%), followed by the peripheral vascular domain (20.3%). No clinical, demographic nor laboratory parameters were significantly associated with damage. Regarding HR-QoL, pain/discomfort, anxiety/depression and usual activities domains were the most frequently impaired in both scales. DIAPS's domains correlated similarly with the EQ-5D-3L and 5L scales' individual domains. Female sex, medical disorders, secondary APS and type of presenting thrombosis (arterial) increased the risk of HR-QoL impairment. Total DIAPS was associated with higher odds of mobility, self-care and pain/discomfort impairment in both EQ-5D-3L and 5L scales but lost its independent risk in multivariable analysis. Conclusion: This external validation of DIAPS reinforces the ability of the score to correlate with HR-QoL while also highlighting risk factors for HR-QoL impairment other than damage accrual. [ABSTRACT FROM AUTHOR]

Introduction: Although RT has improved the survival of the population with ESRD due to all causes, renal outcomes in SLE are controversial. The objective of this study is to describe the characteristics and evolution of the patients and the kidney transplant in LN, and compare it with patients transplanted for other causes. Materials and methods: Retrospective, observational, analytical, single-center study in which records of patients undergoing nephrotransplantation for LN were analyzed. They were compared with a group of patients transplanted at the same center for other causes of ESRD. Results: 41 patients with kidney transplant due to SLE and 89 transplanted due to other causes of ESRD were registered. Graft loss occurred in 12 (29.26%) patients with LN and 34 (38.2%) patients in the comparison group (p =.428). Only one case (4.8%) presented reactivation of the LN in the graft, without graft loss. Median graft survival was 73.1 months in the LN group and 66.3 months in the comparison group (p =.221). A total of 8 (19.5%) patients with LN and 11 (12.4%) without LN died (p =.42), with infections being the main cause in both groups. There were no statistically significant differences between groups in graft and patient survival. In a sub-analysis of 28 patients with LN with aPL study, 4 thrombotic events were observed, in 3 different patients, in the aPL-positive group. There were no statistically significant differences in terms of causes of graft loss and graft survival (positive aFL 75.7 months vs negative aFL 72.7 months, p=.96). There were also no differences in mortality between the groups (p =.61). Conclusion: Patients transplanted for LN did not differ from the control population in terms of graft and patient survival. Infections were the main cause of death, so prophylaxis and vaccination continue to be a fundamental pillar in the prevention of infections in immunocompromised patients. [ABSTRACT FROM AUTHOR]

Despite being some of the most anecdotally well‐known roads to pathogenesis, the mechanisms governing autoimmune rheumatic diseases are not yet fully understood. The overactivation of the cellular immune system and the characteristic development of autoantibodies have been linked to oxidative stress. Typical clinical manifestations, such as joint swelling and deformities and inflammation of the skin and internal organs, have also been connected directly or indirectly to redox mechanisms. The differences in generation and restraint of oxidative stress provide compelling evidence for the broad variety in pathology among rheumatic diseases and explain some of the common triggers and discordant manifestations in these diseases. Growing evidence of redox mechanisms in pathogenesis has provided a broad array of new potential therapeutic targets. Here, we explore the mechanisms by which oxidative stress is generated, explore its roles in autoimmunity and end‐organ damage, and discuss how individual rheumatic diseases exhibit unique features that offer targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Introduction: Thrombotic events are more than twice as common in inflammatory bowel disease patients as in the general population. We report an interesting and rare case of portal vein thrombosis as a venous thromboembolic event in the context of extraintestinal manifestations of Crohn's disease. We also conducted a literature review on portal vein thrombosis associated with inflammatory bowel disease, with the following concepts: inflammatory bowel diseases, ulcerative colitis, Crohn's disease, portal vein, and thrombosis. Case presentation: A 24-year-old Syrian female with active chronic Crohn's disease was diagnosed 11 years ago and classified as A1L3B1P according to the Montreal classification. She had no prior surgical history. Her previous medications included azathioprine and prednisolone. Her Crohn's disease activity index was 390 points. Gastroduodenoscopy revealed grade I esophageal varices, a complication of portal hypertension. Meanwhile, a colonoscopy revealed several deep ulcers in the sigmoid, rectum, and descending colon. An investigation of portal vein hypertension revealed portal vein thrombosis. We used corticosteroids to induce remission, followed by tapering; additionally she received ustekinumab to induce and maintain remission. She began on low-molecular-weight heparin for 1 week, warfarin for 3 months, and then apixaban, a novel oral anticoagulant, after excluding antiphospholipid syndrome. Primary prophylaxis for esophageal varices was not required. After 1 year, she achieved clinical, biochemical, and endoscopic remission. Despite 1 year of treatment, a computed tomography scan revealed no improvement in portal vein recanalization. Conclusion: Portal vein thrombosis is a rare and poorly defined complication of inflammatory bowel disease. It is usually exacerbated by inflammatory bowel disease. The symptoms are nonspecific and may mimic a flare-up of inflammatory bowel disease, making the diagnosis difficult. Portal vein Doppler ultrasound for hospital-admitted inflammatory bowel disease patients may contribute to the diagnosis and management of this complication. [ABSTRACT FROM AUTHOR]

The European Journal of Rheumatology is an open access journal that covers various aspects of rheumatology. It publishes original articles, reviews, case-based reviews, and letters to the editor. The journal is aimed at academicians, practitioners, specialists, and students in the field of rheumatology. The document provides a schedule of sessions and presentations at a conference on autoimmune diseases, covering topics such as COVID-19, lupus, vasculitis, and novel approaches to handling autoimmune diseases. It also contains summaries of presentations on topics related to autoimmune diseases, including myositis, post-COVID syndrome, uveitis, and genetic predisposition to autoimmunity. The document discusses cell therapy, novel therapies, and the impact of environmental factors on autoimmune diseases. It explores the potential of CAR-T cell therapy, mesenchymal stromal cell transplantation, cannabis, therapeutic peptides, and RNA gene expression in the treatment and management of autoimmune diseases. The document also highlights the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), finding that SLE patients have an increased risk of severe COVID-19 and higher mortality rates. The document contains summaries of various research studies and discussions related to autoimmune diseases, covering topics such as inflammatory signals in myeloid cells, cardiovascular risk profile of rheumatoid arthritis patients, and immunonutritional status of patients with systemic lupus erythematosus. It also explores subjects such as autoantib [Extracted from the article]

Objective Transcranial Doppler (TCD) and brain MRI may be useful in evaluating patients with APS, helping to stratify the risk of cerebrovascular ischaemic events in this population. This study aimed to assess the frequency of brain MRI abnormalities in patients with primary antiphospholipid syndrome, secondary antiphospholipid syndrome and SLE and correlate to TCD findings. Methods The study, conducted over four years at two autoimmune disease referral centres, included 22 primary antiphospholipid syndrome patients, 24 secondary antiphospholipid syndrome patients, 27 SLE patients without APS and 21 healthy controls. All participants underwent TCD to assess cerebral haemodynamics, detect microembolic signals and evaluate right-to-left shunts, followed by brain MRI and magnetic resonance angiography. MRI scans were reviewed for acute microembolism, localized cortical infarctions, border infarctions, lacunar infarctions, ischaemic lesions, white matter hyperintensity, micro and macro haemorrhages and arterial stenosis ≥50% of the cervical carotid artery, by two neuroradiologists blinded to the clinical data. Results Brain MRI findings were similar between the groups, except for lacunar infarction, more frequent in patients with secondary antiphospholipid syndrome (P  = 0.022). Patients with intracranial stenosis detected by TCD had a higher frequency of territorial infarction (40% vs 7.5%, P  = 0.02), lacunar (40% vs 11.3%, P  = 0.075) and border zone infarcts (20% vs 1.9%, P  = 0.034). Conclusions Patients with intracranial stenosis presented a higher frequency of territorial, lacunar and border zone infarcts, suggesting that evaluating the intracranial vasculature should not be neglected in patients with APS and stroke. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We present a rare case of primary antiphospholipid syndrome in a 38‐year‐old male who presented with painful digital ischemia. Early initiation of anticoagulation and addition of glucocorticoid led to a significant improvement in the patient. [ABSTRACT FROM AUTHOR]

To evaluate the ovarian reserve (OR) in women with antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE), especially SLE-associated APS, and to determine the association between OR and clinical and laboratory parameters. We compared the antral follicle count (AFC), anticardiolipin antibody, and anti-Müllerian hormone (AMH), inhibin B (INHB), antiphospholipid (aPL) antibody, follicle-stimulating hormone (FSH), progesterone (P), testosterone (T), and estradiol (E2) among patients with primary APS (PAPS), SLE-APS, and SLE who were treated at Jinhua Central Hospital between 2017 and 2020. We conducted correlations and logistic regression analyses to identify the risk factors of OR failure in women with APS. Serum AMH were positively correlated with AFC and INHB in APS patients, and low AMH was independent risk factor for OR decline in APS patients. The ROC curve showed a high accuracy for AMH in the prediction of OR failure. Compared to healthy subjects (HS), patients with PAPS, SLE-APS, and SLE exhibited lower serum AMH, AFC, INHB, and E2 levels and higher FSH and levels (p<0.05). Of all the patients, those with SLE-APS manifested the lowest serum AMH, AFC, INHB, and E2 levels and the highest FSH levels (p<0.05). APS and SLE patients showed lower indications of OR, including AFC and AMH, compared to HS. SLE-APS patients also appeared to have a lower OR than either SLE or PAPS patients. [ABSTRACT FROM AUTHOR]

Objective: This retrospective study aimed to conduct a comprehensive analysis of Turkish Systemic Lupus Erythematosus (SLE) patients of Caucasian ethnicity, focusing on their clinical, immunological, and therapeutic characteristics, damage accural and mortality. Patients and Methods: We carried out a retrospective assessment of 300 SLE patients diagnosed between 2001 and 2017 at Kocaeli University Rheumatology Clinic. Demographic data, clinical manifestations, immunological profiles, treatment approaches, disease-related damage, and survival information were collected. Results: The study population had a significant female predominance (89%) with a mean age of disease onset of 35.4 (SD:13.3) years. Hematological (72.6%) and mucocutaneous (72%) manifestations were the most common clinical findings, followed by arthritis (66.3%). Females had higher frequency of photosensitivity (p = 0.019), malar rash (p < 0.001), and alopecia (p = 0.014). Anti-dsDNA antibodies were detected in 61.6% of patients, while 57% of patients had hypocomplementemia. Secondary antiphospholipid syndrome was observed in 15.3% of patients; the most common manifestations included deep venous thrombosis (32.6%) and cerebrovascular accidents (30.4%). Lupus Nephritis (LN) affected 40.3% of the cohort. The most common pathologic finding was Class IV LN (30.5%). Eventually, 13 (4.3%) patients developed chronic kidney disease (CKD) and 4 had renal replacement therapies. Patients with LN had higher usage of pulse steroids, azathioprin, mycophenolate mofetil, cyclophosphamide, and rituximab (p < 0.001 for each). In the juvenile-onset group (n = 31, 10.3%), an increased occurrence of malar rash (p = 0.009), nephritis (p = 0.034), hypocomplementemia (p = 0.001), positive anti-dsDNA (p = 0.007), anti-Sm (p = 0.046), anti-rib-P (p = 0.014) antibodies were observed. At least one damage parameter was observed in 32.6% patients with musculoskeletal manifestations being the most common. Thirteen patients were diagnosed with various malignancies, with cervical cancer being the most common (4 cases). The total 5 and 10-year survival rates were 92.5% and 86.7%, respectively. However, patients with CKD, had lower survival rates; 75% at 3 years and 60% at 15 years. Regression analysis demonstrated an association of CKD and history of infections with decreased survival (p = 0.02, each). Conclusion: Ethnicity and geography influence the clinical diversity of SLE. Recognizing these disparities is crucial for tailoring patient care. Future inception cohort studies in Turkish SLE patients are necessary to address the limitations of retrospective research. [ABSTRACT FROM AUTHOR]

In systemic lupus erythematosus (SLE), cardiovascular complications are among the leading causes of death. Cardiovascular risk in SLE is even higher in the presence of antiphospholipid antibodies or secondary antiphospholipid syndrome (APS). The aim of this retrospective, single-center study was to investigate the occurrence of antiphospholipid antibodies and non-thrombotic cardiac manifestations in 369 SLE patients. We also assessed the clinical and laboratory characteristics of the patients to reveal the risk factors for cardiac manifestations. Patients were divided into two groups based on the presence of antiphospholipid antibodies (APA); 258 (69.9%) patients were APA positive, and 111 (30.1%) patients were APA negative. Mitral and tricuspid insufficiency, aortic stenosis and pulmonary arterial hypertension were more common in APA-positive patients. Anticardiolipin IgG showed the strongest correlation with any non-thrombotic cardiac manifestations. Based on our results, the adjusted global antiphospholipid syndrome score (aGAPSS) above 8.5 is predictive of valvulopathies and ischemic heart disease, while aGAPSS above 9.5 is predictive of cardiomyopathies. The presence of antiphospholipid antibodies may affect the development of cardiac manifestations in SLE. Periodic cardiological and echocardiographic screening of patients without cardiac complaints, as well as regular monitoring of antiphospholipid antibodies, have great importance during the treatment of SLE patients. [ABSTRACT FROM AUTHOR]

Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disorder, characterised by consistently high levels of antiphospholipid antibodies, thrombosis, and/or pregnancy morbidity. Due to various suspected causes, deficient or insufficient levels of vitamin D in the serum have been reported in patients with PAPS; however, the reports have been sporadic and inconclusive. This systematic review and meta-analysis aimed to comprehensively evaluate the serum vitamin D levels in patients with PAPS compared to controls. A protocol was registered in PROSPERO (Registration No. CRD42019132128) and a systematic literature search was conducted through Google Scholar, PubMed, Web of Science, Scopus, and ScienceDirect databases without restricting language and year. Pooled prevalence, mean difference (MD), and odds ratio (OR) along with 95% confidence intervals (CI) were determined by using a random effects model. Study quality was assessed by the Joana Brigg's Institute (JBI) protocol and publication bias was evaluated by a trim and fill funnel plot, Begg's, and Egger's tests. The pooled prevalence of vitamin D deficiency and insufficiency was found to be 32.2% [95% CI: 16.3–48.2] and 61.5% [95% CI: 40.2–82.8], respectively. Serum levels of vitamin D were considerably lower in the PAPS patients compared to controls (MD: −5.75, 95% CI: −9.73 to −1.77; p = 0.005). Multiple sensitivity analyses showed that the results remained statistically significant, demonstrating the robustness of this meta-analysis. No significant publication bias was detected in determining the MD of serum vitamin D levels in PAPS and controls. In conclusion, PAPS patients had greater rates of vitamin D deficiency or insufficiency, higher frequency of thrombosis, and lower serum vitamin D levels than healthy individuals. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibody (aPL)-persistent positivity is frequent in hemodialysis (HD) patients. Native arteriovenous fistula (AVF) complications such as stenosis and thrombosis are among the most important causes of morbidity and mortality in hemodialysis patients. The association between aPL positivity and AVF thrombosis seems to now be well established. However, whether aPL positivity is associated with other AVF complications, such as maturation failure or stenosis, is not well known. Given the significant impact of AVF failure on patient's prognosis, it is of interest to further investigate this particular point in order to improve prevention, surveillance and treatment, and, ultimately, the patient's outcome. This literature review aims to report the recent literature on aPL-associated native AVF complications. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenic purpura (ITP) is an immune-mediated disorder characterized by the destruction of platelets and megakaryocytes due to autoantibodies against the platelet surface proteins. ITP without any apparent cause of thrombocytopenia is defined as primary ITP, and ITP in the setting of SLE is secondary ITP, which can be diagnosed after excluding other causes of thrombocytopenia by history, physical examination, and laboratory testing. Patients with ITP associated with SLE have higher median platelet count and less bleeding manifestations compared to the patients with primary ITP. It can be very challenging to diagnose primary ITP in SLE patients as other causes of thrombocytopenia including drug-induced thrombocytopenia, antiphospholipid syndrome, and thrombotic microangiopathic process should be ruled out. Corticosteroids are the main modality of treatment. IVIG can be used in severe cases. Splenectomy was found to be less effective in ITP associated with SLE compared to primary ITP. Control of disease activity with immunosuppressive therapy can be helpful in some cases associated with active disease flares in SLE patients. [ABSTRACT FROM AUTHOR]

Vaccine- induced immune thrombocytopenia and thrombosis (VITT) is a rare adverse event occurring after immunization with adenoviral vector-based vaccines against SARS-CoV-2. This life-threatening condition is characterized by thrombocytopenia, systemic activation of coagulation, and anti-platelet factor 4 antibodies, often resulting in extensive venous thrombosis. Arterial thrombosis is less common and mainly affects the aorta, peripheral arteries, heart, and brain. Several cases of ischemic stroke have been reported in VITT patients, frequently being associated with large vessel occlusion (LVO). Here, we present a case of aggressive VITT in a 46-year-old woman with a past mild SARS-CoV-2 infection, who was admitted with a left-middle cerebral artery (MCA) territory stroke and thrombocytopenia eight days after her first dose of the ChAdOx1 nCoV-19 vaccine. The patient developed a diffuse arterial thrombosis with concomitant thrombotic events in the intrahepatic portal branches. The patient's clinical condition worsened rapidly due to a significant enlargement of the ischemic cerebral lesion in the left hemisphere, cerebral herniation, and incipient hydrocephalus requiring decompressive neurosurgery with an unfavorable outcome. Our observations may be indicative of a stroke variant in VITT and highlight the diverse clinical manifestations of the syndrome. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to explore what non-pharmacological interventions have been examined for individuals with antiphospholipid syndrome (APS). Methods: We conducted a systematic literature search of the databases PubMed, Embase, Scopus, Web of Science, CINAHL, and ClinicalTrials.gov from 1983–Feb. 2023. Our scoping review included studies that examined non-pharmacological interventions for individuals with APS using patient-reported outcome measures. We excluded studies that reported physiological outcomes only. Results: The review yielded one case study on the safety and efficacy of an exercise program for a 15-year-old male with secondary APS using physiological and patient-reported outcome measures. Despite the lack of evidence of non-pharmacological interventions for individuals with APS, one excluded study reported that individuals with APS want guidance about physical activity and exercise. We also found several types of potentially relevant non-pharmacological interventions for individuals with lupus, a disease that often co-occurs with APS. Conclusions: Non-pharmacological interventions may offer a solution for addressing some non-thrombotic or non-obstetric APS symptoms, such as neurological, physical, and cognitive symptoms that are not well-controlled by anticoagulation. Due to the unique risks associated with APS, research is needed to determine the safety and efficacy of non-pharmacological interventions, particularly those involving exercise. Adopting a comprehensive, multidisciplinary approach to managing patients with APS and involving rehabilitation professionals, who are experts in the design and delivery of non-pharmacological interventions, may provide a foundation for developing and testing novel interventions that improve health outcomes while also fulfilling unmet needs reported by patients. [ABSTRACT FROM AUTHOR]

Russell Viper Venom (RVV) is widely used as a diagnostic test for antiphospholipid syndrome (APS). But the history of how this venom came to be discovered is well known. Dr Patrick Russell is responsible for the identification of the venom during his work on snake bites in India while Dr Robert Macfarlane used it to staunch bleeding in persons with haemophilia. The ability to directly activate factor X led RVV to the laboratory diagnosis of APS. More recently, it has come back to clinical world with a potential for an engineered factor X activator from RVV to be used in the treatment of haemophilia. [ABSTRACT FROM AUTHOR]

Proteins in the plasma/serum mirror an individual's physiology. Circulating extracellular vesicles (EVs) proteins constitute a large portion of the plasma/serum proteome. Thus, deep and unbiased proteomic analysis of circulating plasma/serum extracellular vesicles holds promise for discovering disease biomarkers as well as revealing disease mechanisms. We established a workflow for simple, deep, and reproducible proteome analysis of both serum large and small EVs enriched fractions by ultracentrifugation plus 4D-data-independent acquisition mass spectrometry (4D-DIA-MS). In our cohort study of obstetric antiphospholipid syndrome (OAPS), 4270 and 3328 proteins were identified from large and small EVs enriched fractions respectively. Both of them revealed known or new pathways related to OAPS. Increased levels of von Willebrand factor (VWF) and insulin receptor (INSR) were identified as candidate biomarkers, which shed light on hypercoagulability and abnormal insulin signaling in disease progression. Our workflow will significantly promote our understanding of plasma/serum-based disease mechanisms and generate new biomarkers. A workflow is established for simple, deep, and reproducible proteomic analysis of serum EVs enriched fractions by 4D-DIA-MS, achieving 4270 and 3328 proteins quantified from large and small EVs enriched fractions, respectively, in a cohort study. [ABSTRACT FROM AUTHOR]

Background: Alterations of the trimethylation of histone 3 lysine 4 (H3K4me3) mark in monocytes are implicated in the development of autoimmune diseases. Therefore, the purpose of our study was to elucidate the role of H3K4me3‐mediated epigenetics in the pathogenesis of antiphospholipid syndrome (APS). Methods: H3K4me3 Cleavage Under Targets and Tagmentation and Assay for Transposase‐Accessible Chromatin were performed to determine the epigenetic profiles. Luciferase reporter assay, RNA immunoprecipitation, RNA pull‐down, co‐immunoprecipitation and chromatin immunoprecipitation were performed for mechanistic studies. Transmission electron microscopy and propidium iodide staining confirmed cell pyroptosis. Primary monocytes from patients with primary APS (PAPS) and healthy donors were utilised to test the levels of key molecules. A mouse model mimicked APS was constructed with beta2‐glycoprotein I (β2GPI) injection. Blood velocity was detected using murine Doppler ultrasound. Results: H3K4me3 signal and open chromatin at the ARID5B promoter were increased in an in vitro model of APS. The epigenetic factor ARID5B directly activated LINC01128 transcription at its promoter. LINC01128 promoted the formation of the BTF3/STAT3 complex to enhance STAT3 phosphorylation. Activated STAT3 interacted with the NLRP3 promoter and subsequently stimulated pyroptosis and apoptosis. ARID5B or BTF3 depletion compensated for LINC01128‐induced pyroptosis and apoptosis by inhibiting STAT3 phosphorylation. In mice with APS, β2GPI exposure elevated the levels of key proteins of pyroptosis and apoptosis pathways in bone marrow‐derived monocytes, reduced the blood velocity of the ascending aorta, increased the thrombus size of the carotid artery, and promoted the release of interleukin (IL)‐18, IL‐1β and tissue factor. Patients with PAPS had the high‐expressed ARID5B and LINC01128, especially those with triple positivity for antiphospholipid antibodies. Moreover, there was a positive correlation between ARID5B and LINC01128 expression. Conclusion: This study indicated that ARID5B/LINC01128 was synergistically upregulated in APS, and they aggravated disease pathogenesis by enhancing the formation of the BTF3/STAT3 complex and boosting p‐STAT3‐mediated pyroptosis and apoptosis, thereby providing candidate therapeutic targets for APS. Highlights: The H3K4me3 mark and chromatin accessibility at the ARID5B promoter are increased in vitro model mimicked APS.ARID5B‐mediated LINC01128 induces pyroptosis and apoptosis via p‐STAT3 by binding to BTF3.ARID5B is high‐ expressed in patients with primary APS and positively correlated with LINC01128 expression.OICR‐9429 treatment mitigates pyroptosis and related inflammation in vivo and in vitro models mimicked APS. [ABSTRACT FROM AUTHOR]

Background: While the prevalence of antiphospholipid antibodies (aPL) in venous and arterial thrombotic events had already been estimated by previous studies, the prevalence of aPL in subjects with Thrombotic Microangiopathy (TMA) is still not fully elucidated. Thus, we conducted a systematic review to estimate the frequency of aPL in subjects with biopsy-proven renal TMA. Methods: We conducted in the PubMed database a search for English-language studies investigating the presence of aPL in subjects with biopsy-proven renal TMA from January 1985 to December 2022. Keywords used in the search included: 'antiphospholipid syndrome', 'antiphospholipid antibodies' and 'thrombotic microangiopathy'. Cohorts of HUS patients were excluded due to the risk of over-estimating the prevalence of aPL in these populations. The median frequency for positive aPL including anticardiolipin antibodies (aCL), antibodies against β2-glycoprotein-I (anti-β2GPI) and lupus anticoagulant (LA) was then calculated. Results: 522 articles were identified through the literature search. Six studies, assessing the prevalence of aPL in 211 subjects with renal TMA, were retrieved. The overall aPL prevalence was estimated as 24.4% (range 22–56). The estimated prevalence of aCL (IgG/IgM), anti-β2GPI, (IgG/IgM) and LA was 4.0% (range 3–27), 4.0% (range 3–16) and 18.9% (range 13–25), respectively. APS was diagnosed in 16.3% (range 11–29) of the patients. Of note, a high level of heterogeneity was observed when comparing the reported aPL profiles for each study. Conclusions: This comprehensive systematic analysis of studies investigating the prevalence of aPL in renal TMA showed that, despite the high heterogeneity of the included studies, aPL are present in about one case out of four renal-TMA cases. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which is associated with nonspecific respiratory syndromes, varying from mild symptoms of upper airway to required mechanical ventilation hypoxemia. A unique feature of this disease is COVID-19-associated coagulopathy (CAC) that linked with disease severity and hospital mortality. These patients have a profound hypercoagulable state and in patients with severe type arterial and venous thrombotic events are frequent. Abnormal coagulation parameters such as activated partial thromboplastin time (aPTT) were observed in patients with COVID-19. Regarding the above finding it could be considered as a reason to avoid anticoagulation at the both doses of therapeutic and prophylactic. A prolonged aPTT may indicate a coagulation factor deficiency or inhibitor of coagulation, which can be specific (antibody to factor VIII) or nonspecific (lupus anticoagulant, LA). LA can affect laboratory tests of blood coagulation, but is not usually associated with bleeding; however, it can be associated with thrombotic risk as a part of the antiphospholipid syndrome. In a phospholipid concentration-dependent manner LA recognizes a type of antiphospholipid antibodies (aPLs) that prolong clotting tests. In patients with antiphospholipid syndrome (APS) LA is considered as one of the laboratory criteria representing a significant risk factor of both thrombosis and pregnancy morbidity. Similarities between some of the pathophysiological features of COVID-19 and APS has been focused in several reports particularly in the most severe form, catastrophic APS. This study aimed to evaluate the effect of LA on the incidence of thrombophilia in patients with COVID-19, as well as its impact on the inflammation and finally the mortality final rate. [ABSTRACT FROM AUTHOR]

Stroke is considered one of the most common and life-threatening manifestations of antiphospholipid syndrome (APS), which leads to high mortality and permanent disability. This study investigated the prevalence and the potential risk factors of stroke in APS. We enrolled 361 APS patients retrospectively from 2009 to 2022 at Peking University People's Hospital. Stroke was found in 25.8% (93/361) of the participants. The multivariate logistic regression showed that hypertension, diabetes, livedo reticularis, and other central nervous system involvements were significant related factors for stroke. The use of hydroxychloroquine appeared to relate to a lower incidence of stroke. During a median follow-up of 3.0 years, 11.8% (11/93) of the individuals with a previous stroke developed stroke recurrence, and thrombocytopenia seemed to be a predictor of stroke recurrence. [ABSTRACT FROM AUTHOR]