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Introduction: The antiphospholipid syndrome (APS) is defined by the occurrence of venous and/or arterial thrombosis and/or pregnancy-related morbidity, combined with the presence of antiphospholipid antibodies (aPL) and/or a lupus anticoagulant (LAC). Large, controlled, intervention trials in APS are limited. This paper aims to provide clinicians with an expert consensus on the management of APS., Methods: Relevant papers were identified by literature search. Statements on diagnostics and treatment were extracted. During two consensus meetings, statements were discussed, followed by a Delphi procedure. Subsequently, a final paper was written., Results: Diagnosis of APS includes the combination of thrombotic events and presence of aPL. Risk stratification on an individual base remains challenging. 'Triple positive' patients have highest risk of recurrent thrombosis. aPL titres > 99th percentile should be considered positive. No gold standard exists for aPL testing; guidance on assay characteristics as formulated by the International Society on Thrombosis and Haemostasis should be followed. Treatment with vitamin K-antagonists (VKA) with INR 2.0-3.0 is first-line treatment for a first or recurrent APS-related venous thrombotic event. Patients with first arterial thrombosis should be treated with clopidogrel or VKA with target INR 2.0-3.0. Treatment with direct oral anticoagulants is not recommended. Patients with catastrophic APS, recurrent thrombotic events or recurrent pregnancy morbidity should be referred to an expert centre., Conclusion: This consensus paper fills the gap between evidence-based medicine and daily clinical practice for the care of APS patients.

In this guideline, recurrent miscarriage has been defined as three or more first trimester miscarriages. However, clinicians are encouraged to use their clinical discretion to recommend extensive evaluation after two first trimester miscarriages, if there is a suspicion that the miscarriages are of pathological and not of sporadic nature. Women with recurrent miscarriage should be offered testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, prior to pregnancy. [Grade C] Women with second trimester miscarriage may be offered testing for Factor V Leiden, prothrombin gene mutation and protein S deficiency, ideally within a research context. [Grade C] Inherited thrombophilias have a weak association with recurrent miscarriage. Routine testing for protein C, antithrombin deficiency and methylenetetrahydrofolate reductase mutation is not recommended. [Grade C] Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage(s) and in any second trimester miscarriage. [Grade D] Parental peripheral blood karyotyping should be offered for couples in whom testing of pregnancy tissue reports an unbalanced structural chromosomal abnormality [Grade D] or there is unsuccessful or no pregnancy tissue available for testing. [GPP] Women with recurrent miscarriage should be offered assessment for congenital uterine anomalies, ideally with 3D ultrasound. [Grade B] Women with recurrent miscarriage should be offered thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies. [Grade C] Women with recurrent miscarriage should not be routinely offered immunological screening (such as HLA, cytokine and natural killer cell tests), infection screening or sperm DNA testing outside a research context. [Grade C] Women with recurrent miscarriage should be advised to maintain a BMI between 19 and 25 kg/m 2 , smoking cessation, limit alcohol consumption and limit caffeine to less than 200 mg/day. [Grade D] For women diagnosed with antiphospholipid syndrome, aspirin and heparin should be offered from a positive test until at least 34 weeks of gestation, following discussion of potential benefits versus risks. [Grade B] Aspirin and/or heparin should not be given to women with unexplained recurrent miscarriage. [Grade B] There are currently insufficient data to support the routine use of PGT-A for couples with unexplained recurrent miscarriage, while the treatment may carry a significant cost and potential risk. [Grade C] Resection of a uterine septum should be considered for women with recurrent first or second trimester miscarriage, ideally within an appropriate audit or research context. [Grade C] Thyroxine supplementation is not routinely recommended for euthyroid women with TPO who have a history of miscarriage. [Grade A] Progestogen supplementation should be considered in women with recurrent miscarriage who present with bleeding in early pregnancy (for example 400 mg micronised vaginal progesterone twice daily at the time of bleeding until 16 weeks of gestation). [Grade B] Women with unexplained recurrent miscarriage should be offered supportive care, ideally in the setting of a dedicated recurrent miscarriage clinic. [Grade C]., (© 2023 Royal College of Obstetricians and Gynaecologists.)

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]

Purpose: We aimed to evaluate adherence and persistence to warfarin therapy among patients with antiphospholipid syndrome (APS) and investigate the association between adherence and thrombotic events in those patients., Methods: We conducted a retrospective cohort study using the Japan Medical Data Center claims database from 2005 to 2018. Patients with APS receiving warfarin treatment were included in this study. Adherence and persistence were evaluated using the proportion of days covered (PDS) and refill gap methods, respectively. Demographic characteristics of patients were obtained. Kaplan-Meier curves with log-rank tests and Cox regression models were used to examine the association between adherence or persistence and time to thrombotic events., Results: A total of 186 patients (mean age: 46.5 ± 12.4 years, females 68.8%) were included in this study. No significant differences were observed in risk factors for thrombosis and cardiovascular diseases among groups. Most patients were adherent (91.4%) and persistent (88.2%) to warfarin treatment. Adherent and persistent patients had a significantly higher rate of thrombotic event-free survival than nonadherent and nonpersistent patients (p < 0.05). Multivariable Cox regression showed that the risk of thrombotic events was higher in nonadherent patients (with a hazard ratio of 3.23 [95% confidence interval CI: 1.15-9.11]) and in nonpersistent patients (with a hazard ratio of 3.45 [95% CI: 1.35-8.82])., Conclusions: In patients with APS, nonadherence and nonpersistence to warfarin treatment was associated with a higher risk of thrombotic events, suggesting the careful monitoring of those patients., (© 2021 John Wiley & Sons Ltd.)

Catastrophic antiphospholipid syndrome (CAPS) is an unusual complication of antiphospholipid syndrome (APS) occurring in about 1% of patients. If left untreated, mortality can be as high as 50%. Therapy of APS and its complication CAPS is hampered by the lack of validated prospective, controlled, intervention clinical trials, although there is consensus that treatment should include anticoagulation therapy. But there are issues that need to be addressed such as duration and intensity of therapy. The present report describes our experience in 7 patients with CAPS in whom anticoagulation was discontinued after 6 months of therapy. During an average follow-up of 5.5 years, only 2 patients exhibited one episode each of recurrent venous thrombosis, but none of the patients in whom anticoagulation was discontinued experienced recurrent CAPS.Key Points• Discontinuation of long-term anticoagulation therapy in CAPS patients was not followed by recurrence of CAPS.

Background: Catastrophic antiphospholipid syndrome (CAPS) is an uncommon, often fatal, variant of the antiphospholipid syndrome (APS) that results in a widespread coagulopathy and high titres of antiphospholipid antibodies (aPL) and affects predominantly small vessels supplying organs with the development of multiorgan failure. It remains unclear why some patients develop the typical clinical picture of APS (thrombosis of large vessels), whereas others show the development of progressive microthrombosis, which the authors called "thrombotic storm" and multiple organ failure, that is, CAPS., Materials and Methods: Since 2001-2016, we discovered 17 patients with CAPS development., Conclusion: CAPS is life-threatening condition, but optimal treatment for CAPS is not developed yet and the mortality rate is as high as 30%-40%.

Background: Antiphospholipid syndrome is an autoimmune disorder characterized by recurrent vascular thrombosis and pregnancy losses in the presence of persistently positive antiphospholipid antibodies. Bibliometric analysis and altmetric analysis are methods of analyzing academic productivity and influence. Currently, the assessment of antiphospholipid syndrome through the above analyses is lacking. This study investigated the quantity and quality of studies in the field of antiphospholipid syndrome and revealed the characteristics of worldwide productivity on this disease by the bibliometric analysis and altmetric analysis. Methods: The terms "APS," "antiphospholipid syndrome," "antiphospholipid-antibody syndrome," and "Hughes syndrome" were searched on the Web of Science Core Collection from January 1, 2011, to December 31, 2021. Original articles and reviews were selected. We set the filters as "English." Results and conclusion: A total of 1818 articles were retrieved from 68 countries, of which 20 met the criteria of major active countries. High-income countries contributed 1341 articles (73.48%). The number of articles annually increased significantly in the 10-year period (P < 0.001). The USA (253, 13.91%) was the most productive country. Adjusted by population, Serbia was top of the list. According to the gross domestic product analysis, Serbia ranked first. The most used keywords such as thrombosis and antiphospholipid antibodies were presented by keywords analyses. A content analysis found antithrombotic and anticoagulant therapy as research hotspots. A significant correlation was detected between average citations and altmetric attention scores (P = 0.002) and Mendeley readers count (P < 0.001). From 2011 to 2021, the number of global articles increased rapidly. Most papers came from high-income countries. The relationship between the bibliometric and altmetric analyses were basically consistent; therefore the two can prove/complement each other. Key points • We revealed the global productivity characteristics of the papers related to antiphospholipid syndrome by using the methods of bibliometric analysis and altmetric analysis. • We found the most selected articles that describe the treatment of antiphospholipid syndrome, especially antithrombotic and anticoagulant treatments, which may be the current research hotspot. [ABSTRACT FROM AUTHOR]

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]

Background: Given the catastrophic results of antiphospholipid syndrome (APS) left untreated, the possible role of non-criteria antiphospholipid (aPL) in the diagnosis of seronegative (SN)-APS patients, and its impact on the timely treatment of people with SNAPS, the present review aimed to gather the available literature up to 2022 focusing on the role of non-criteria aPL in the diagnosis of SN cases suspected of APS using non-criteria aPL. Methods: All published papers focusing mainly on the diagnosis of the SN-APS patients by non-criteria aPL were searched in four databases of PubMed, Scopus, Medline, and Web of Sciences, followed by manual search up to 20 February 2022 using such keywords as "Antiphospholipid Syndrome", "Seronegative", and "Non-Criteria". Finally, 15 studies were selected after the detailed evaluation of the full-text versions. Results: Based on the obtained results of our study, 24% to 81.9% of the SN-APS cases were positive for at least one isotype of non-criteria aPL. Thrombophilia events were more frequent in the APS population, compared to SN-APS; however, obstetric manifestations were more frequent in the SN-APS population, compared to seropositive-APS. Antivimentin/cardiolipin and antiphosphatidylserine/prothrombin IgG/IgM were introduced as the best non-criteria aPL to detect seronegative cases that were correlated with clinical manifestations. Conclusion: It seems that a combination of testing for non-criteria aPL should be performed for cases suspected of APS with negative criteria markers. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome is an autoimmune disorder which is characterized by the presence of heterogeneous antiphospholipid antibodies. There is an evidence on antiphospholipid (aPL) antibodies related to thromboembolic events in cancer patients. In fact, the thrombotic complications in patients with malignancy occur at a rather high frequency, compared to other risk factors. In parallel with standard therapies available, there is need of case-by-case monitoring of each patient and the introduction of new therapies and need for more clinical trials which will address many questions for the optimal management of patients. This paper presents a basic review of the literature on the aPL antibodies associated with cardiovascular disease and cancer, as well as its complications, which are reported so far in the bibliography., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Antiphospholipid Antibody Syndrome (APS) is a complex autoimmune disorder that includes a combination of laboratory criteria and clinical events (thrombosis, pregnancy complications). Accurate classification is essential, as APS patients may have limited oral anticoagulant options and requires indefinite anticoagulation. The prevalence of inaccurate APS misclassification is unknown. This study sought to determine the proportion of patients in an academic health-system who formally met APS criteria., Methods: This retrospective cohort study included any patient within the University of Utah Health system who had an International Classification of Diseases-10 code for APS, between January 1, 2016 and June 30, 2020. Manual chart review was performed to assess the appropriateness of the APS classification by laboratory and clinical criteria., Results: Of the 184 patients identified, 59 (32.1 %) formally met APS criteria, while 69 (37.5 %) did not meet criteria. The remaining 56 (30.4 %) patients lacked enough information in their medical records to decide on appropriateness of APS classification. The most prevalent reason for inappropriate APS classification in the 69 patients identified was incorrect interpretation of lab values as positive (62; 89.9 %), followed by lack of repeat confirmation testing (32; 46.4 %)., Conclusion: The results of this single-center study indicate that only one-third of patients with presumed APS met classification criteria. This was predominantly due to incorrect collection or interpretation of APS laboratory data. One-third had insufficient medical record data to determine APS classification, which impairs clinical decision-making. This suggests more education or implementation of anticoagulation stewardship is needed to ensure accurate APS classification and proper management of anticoagulation therapy., 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 © 2022 Elsevier Ltd. All rights reserved.)

Objective: The primary objective of this study was to explore whether antisense oligonucleotides (ASOs) that reduce LncNR&#95;040117 expression in patients with antiphospholipid antibody syndrome (APS)-induced recurrent pregnancy loss (RPL), and further decrease apoptosis and improve trophoblasts invasion through mitogen-activated protein kinase (MAPK) pathways. This paper aimed to provide a new strategy to treat APS-induced RPL., Methods: In this study, we used quantitative reverse transcription-polymerase chain reaction (RT-qPCR) to analyze the expression level of LncNR 040117 in HTR-8/SVneo cells following transfection with ASOs. Then we utilized Western blotting to test the expression levels of interleukin-1β (IL-1β), intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and key molecules of MAPK pathways, including the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and p38. In addition, we examined the HTR-8/SVneo cells apoptosis by cell apoptosis assay, and migration and invasion by transwell antibody assay. Each experiment was repeated three times. The data are presented as the means ± SDs, and statistical comparisons were performed using Student's t-test. p  < 0.05 was considered significant., Result: Transfected with ASOs, LncNR&#95;040117 was downregulated in trophoblasts compared with APS-induced RPL patients. And LncNR&#95;040117 low expression induced IL-1β and downstream adhesion molecules ICAM-1 and VCAM-1expression level decreased, as well as MAPK pathways downregulation, including the ERK pathway, JNK pathway and p38/MAPK pathway. Furthermore, all these changes resulted in decreased apoptosis and increased migration and invasion of trophoblasts., Conclusion: This study indicated that ASOs that decrease LncNR&#95;040117 expression can reduce apoptosis and enhance the invasion and migration of trophoblasts by regulating the MAPK pathway.

Autoimmune diseases have specific pathophysiologic mechanisms leading to an increased risk of arterial and venous thrombosis. The risk of venous thromboembolism (VTE) varies according to the type and stage of the disease, and to concomitant treatments. In this review, we revise the most common autoimmune disease such as antiphospholipid syndrome, inflammatory myositis, polymyositis and dermatomyositis, rheumatoid arthritis, sarcoidosis, Sjogren syndrome, autoimmune haemolytic anaemia, systemic lupus erythematosus, systemic sclerosis, vasculitis and inflammatory bowel disease. We also provide an overview of pathophysiology responsible for the risk of VTE in each autoimmune disorder, and report current indications to anticoagulant treatment for primary and secondary prevention of VTE., 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.)

Introduction: Low-grade endotoxemia is associated with systemic inflammation, enhanced oxidative stress and cardiovascular events in different clinical settings, but its possible role as "second hit" in patients with primary antiphospholipid syndrome (PAPS) has never been investigated., Purpose: To evaluate the relationship between plasma lipopolysaccharide (LPS) levels, oxidative stress markers and risk of thrombosis in the prospective multicenter ATHERO-APS study., Methods: Baseline LPS, soluble NADPH-oxidase 2-derived peptide (sNOX-dp), H 2 O 2 production, hydrogen peroxide breakdown activity (HBA), and nitric oxide (NO) bioavailability were compared in 97 PAPS, 16 non-thrombotic aPL carriers and 21 controls (CTRL) matched for age and sex. Correlations among laboratory variables were explored by Rho Spearman's correlation (rS). Cox-regression analysis was performed to assess the association between LPS and risk for a composite outcome of cardiovascular death, venous and arterial thromboembolism., Results: In the whole cohort (median age 51 years (IQR 43-60), 72 % female), PAPS demonstrated higher levels of LPS, sNOX-dp and H 2 O 2 and lower levels of NO and HBA compared to non-thrombotic aPL carriers and CTRL. LPS levels were inversely correlated with HBA (rS: -0.295, p = 0.001) and NO (rS: -0.322, p < 0.001) and directly correlated with sNOX-dp (rS:0.469, p < 0.001) and H 2 0 2 (rS:0.282, p < 0.001). PAPS showed higher levels of LPS, sNOX-dp and H 2 O 2 and lower levels of NO and HBA compared to aPL carriers and CTRL. After a 4.7 years follow-up of, 11 composite outcomes were reported in PAPS (2.5 per 100 patient-years) while none was observed in aPL carriers. On Cox-regression analysis, patients with LPS above the median (>23.1 pg/ml) had a 5-fold increased risk of composite outcome compared to those with LPS below the median, after adjustment for sex, age, diabetes, and global antiphospholipid syndrome score., Conclusion: Low-grade endotoxemia is associated with an increased oxidative stress and a higher risk of thrombosis in PAPS. Its prognostic value in carriers needs to be investigated in larger cohorts., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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]

Introduction: We aimed to describe the pattern of placental injuries in women with systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS) and non-criteria obstetric APS (NC-OAPS), and to correlate the placental findings with the occurrence of adverse perinatal outcomes., Methods: The perinatal outcomes and placental findings of pregnancies of women with SLE, APS, and NC-OAPS and gestational-age matched healthy controls were analyzed and classified according to the 2015 Redline - Classification of placental lesions., Results: 91 women with SLE, APS, and NC-OAPS and 91 controls were included. Mean values of placental weight differed between groups, being significantly lower in NC-OAPS and APS groups compared to controls. Furthermore, 14.3% of placentas in the APS group were under the 3rd percentile, which was significantly higher in comparison with other groups. Regarding histopathological placental findings, maternal-side malperfusion was significantly increased in APS (46.4%) compared to NC-OAPS (14.3%) and SLE (9.5%). Fetal-side maldevelopment was significantly increased in NC-OAPS (19.1%) compared to controls (1.1%) and SLE (2.4%). A significantly increased prevalence of adverse perinatal outcomes (APOs) was observed in all studied groups compared to healthy controls (controls 3.3%, SLE 52.4%, NC-OAPS 57.1%, APS 64.3%). Overall, both maternal (OR 6.8, 95%CI 2.1-22) and fetal-side (OR 4.1, 95%CI 1.3-13.5) lesions were significantly associated with APO. Maternal malperfusion and fetal maldevelopment were the lesions most strongly associated with APOs., Discussion: Pregnant women with SLE, APS, or NC-OAPS showed a different pattern of histopathological findings. Compared to controls, SLE, APS, and NC-OAPS conferred an increased risk of APOs that was strongly associated with placental maternal-side malperfusion and fetal-side maldevelopment., 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 Ltd.)

We read with interest the paper by Lee I et al i .[1] in which they describe widespread microvascular damage marked by endothelial cell damage/activation, microthrombi, complement activation, and disruption of the blood-brain barrier (BBB). Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein. [Extracted from the article]

Adrenal hemorrhage is a rare, but important, diagnosis to recognize, in particular when there is involvement of both adrenal glands. Bilateral adrenal hemorrhage can in fact lead to adrenal insufficiency, with dramatic consequences if not promptly recognized and treated. It is normally caused by systemic conditions that lead to the vasoconstriction and thrombosis of the adrenal vein. Oftentimes, the clinical diagnosis of this condition can be very challenging, as its signs and symptoms are generalized and nonspecific (abdominal pain, nausea, and fatigue). Here, we present the cases of two patients admitted to the Emergency Department in 2016 and 2022 with acute abdominal pain, having recently undergone surgery and subsequently prescribed low-molecular-weight heparin. In both cases, laboratory results revealed neutrophilic leukocytosis and an unexplained anemia. Due to the persistence of abdominal pain despite medication, a CT scan was performed, showing an enlargement of both adrenal glands suggestive of bilateral adrenal hemorrhage. Adrenal function was tested that correlated with a diagnosis of adrenal insufficiency, and both patients were promptly treated with parenteral hydrocortisone as a result. On 5 years' follow-up from the acute event, the second patient's adrenal function had returned to normal, and he has not needed further adrenal replacement therapy; the first patient however demonstrated persistence of adrenal failure requiring replacement therapy. In this paper, through our experience and a literature analysis, we will aim to outline some clues to identify patients at potential risk of bilateral adrenal hemorrhage. [ABSTRACT FROM AUTHOR]

To optimize patient prognosis, patient needs, including unmet needs, should be adequately assessed. However, such needs are more challenging to report and, consequently, more likely to go unmet compared with the needs reported by physicians. We aimed to determine the appropriate direction of future research on unmet medical needs in rheumatic diseases in Japan by conducting a literature review. We searched PubMed and Web of Science using 23 terms linked to unmet medical needs for major rheumatic diseases in Japan. Further, we collected articles on health-related quality of life and investigated the scales used for assessment, as well as whether the terms "unmet needs" or "unmet medical needs" were used. We identified 949 papers on 10 diseases, including systemic lupus erythematosus, systemic sclerosis, dermatomyositis, juvenile idiopathic arthritis, adult-onset Still's disease, antiphospholipid syndrome, mixed connective tissue disease, Takayasu arteritis, Sjögren's syndrome, and Behçet's disease; 25 of the 949 papers were selected for full-text review. Fifteen articles on five diseases were related to health-related quality of life. The term "unmet needs" was used in only one article. Six out of 15 studies used the 36-item short form survey, whereas the scales used in other studies differed. The optimal treatment plan determined by a physician may not necessarily align with the best interests of the patient. In clinical research, cross sectional and standardized indicators of health-related quality of life should be employed along with highly discretionary questionnaires to assess and optimize resource allocation in healthcare and simultaneously achieve patient-desired outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Antiphospholipid syndrome is an autoimmune disease characterized by pregnancy-related morbidity, related to persistent positivity of antiphospholipid antibodies (APL). One of the characteristics of pregnancy-related morbidity in patients with antiphospholipid syndrome is recurrent spontaneous abortion (RSA). This study aimed to examine the mechanism through which metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) regulates methyl-CpG-binding domain protein 4 (MBD4) expression in APL-positive RSA., Methods: Clinical samples were subjected to microarray analysis to filter differentially expressed genes. RSA mice with APL positivity were generated, followed by adenoviral vector injection to artificially upregulate MALAT1. The effects of MALAT1 on the biological behavior of trophoblast cells were assessed. The downstream mechanism of MALAT1 was analyzed using subcellular fractionation and bioinformatics prediction, and the relationship between MALAT1 and CREB binding protein (CREBBP) or MBD4 was investigated in trophoblast cells., Results: MALAT1 was downregulated in APL-positive RSA patients. MALAT1 was predominantly localized in the nucleus and recruited CREBBP to mediate the MBD4 transcription. In the APL-positive RSA mice overexpressing MALAT1, the expression of soluble Fms-related tyrosine kinase 1 and anticardiolipin antibody and the embryonic resorption rate were decreased, indicating that MALAT1 reduced the occurrence of RSA in mice. Moreover, MALAT1 enhanced proliferation, migration, and invasion of trophoblast cells through recruiting CREBBP to promote MBD4 expression. Silencing of CREBBP or MBD4 increased embryonic resorption rate in RSA mice overexpressing MALAT1., Discussion: MALAT1 suppresses APL-positive RSA by promoting MBD4 transcription through recruitment of CREBBP to the MBD4 promoter region., 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 Ltd. All rights reserved.)

Currently, the guidelines for the prevention of atherosclerosis in patients with antiphospholipid syndrome (APS) do not differ substantially from those in the general population. We aimed to assess the risk of subclinical atherosclerosis in patients with APS and subjects with antiphospholipid antibody (aPL) positivity. Systematic literature search was conducted through Medline and Scopus until January 2023. Random effects meta-analyses were performed to examine the differences in markers of subclinical atherosclerosis between APS patients, subjects positive for aPLs and healthy controls. Patients with APS had significantly higher values of common carotid artery (CCA) intima-media thickness (IMT) (MD = 0.07 mm; P < 0.0001), internal carotid artery IMT (MD = 0.06 mm; P < 0.01), carotid bifurcation IMT (MD = 0.14 mm; P < 0.01) and were more frequently diagnosed with atherosclerotic plaques compared to controls (OR = 3.73; P < 0.01). Similarly, APS patients showed a decreased flow and nitrate-mediated dilation (MD = -4.52 %; <0.01, MD = -1.25 %; P < 0.05, respectively). Interestingly, comparable were the results for subjects with aPL positivity, who had higher CCA-IMT (MD = 0.06 mm; P < 0.01) and higher prevalence of atherosclerotic plaques (OR = 2.59; P = 0.08) compared to controls. Sensitivity analysis conducted on primary APS patients revealed that the risk of atherosclerosis is associated with APS per se and is not exclusively driven by other underlying conditions. Patients with APS and subjects with aPLs have an increased risk of subclinical atherosclerosis and require early and disease-specific prevention of atherosclerosis., 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 Inc. All rights reserved.)

Objective: There is a limited understanding of racial disparities in adverse pregnancy outcomes (APO) among women with rheumatic diseases. The aim of our study was to conduct a systematic literature review to evaluate the impact of race on APO in women with rheumatic diseases., Methods: Databases were searched to find reports of APO stratified by race among women with rheumatic diseases. The initial searches were conducted in July 2020 and updated in March 2021. Of the final included articles, the full text was reviewed, and data was extracted from each study using a standard data abstraction form., Results: Ten studies with a total of 39,720 patients met our eligibility criteria. There was a greater propensity for APO in racial minorities with rheumatic diseases compared to their White counterparts. Among women with systemic lupus erythematosus (SLE), Black women had the highest odds of APOs, particularly those with a concomitant diagnosis of antiphospholipid syndrome. Pooled meta-analysis could not be done due to multiple factors, including heterogeneity between studies., Conclusion: Racial minorities with rheumatic diseases are more prone to APO compared to their White counterparts. One limitation is the lack of standardized criteria for APO, which prohibited direct comparison between studies. There is also a paucity of data looking at APOs among women with rheumatic diseases other than SLE. Further research is needed to explore the drivers of these racial disparities to guide targeted solutions for those in the greatest need., 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 Inc. All rights reserved.)

Objectives: Neurological manifestations compatible with small vessel brain lesions (SVBL), such as migraine, cognitive impairment, seizures, and transverse myelitis, may be related to antiphospholipid syndrome (APS) and patients could need APS therapies even though they do not fit into thrombosis or obstetric morbidity. Furthermore, extra-criteria antiphospholipid antibodies (aPL) provide an increase in sensitivity in patients with clinical manifestations related to APS but negative for IgG/IgM anticardiolipin (aCL), anti-β2 glycoprotein I (aβ2GPI), and lupus anticoagulant, which are the antibodies included in the classification criteria for APS., Methods: We determined extra-criteria aPL in 65 SVBL patients with neurological traits and Magnetic Resonance Imaging suggestive of APS but negative for APS classification criteria, 47 of whom were prospectively followed and tested over three years. A group of 95 patients with autoimmune diseases (AD) but without clinical traits of APS was also studied., Results: A persistent presence of extra-criteria aPL was detected in 27.7% of patients: 12.77% IgM anti- prothrombin (PT), 6.38% IgG anti-PT, 6.38% IgM anti-phosphatidylethanolamine (PE), 4.26% IgA aβ2GPI, 2.13% IgG anti-phosphatidylserine/prothrombin (PS/PT) and 2.13% IgM anti-PS/PT. There was a tendency towards a higher prevalence of these aPL in SVBL patients than in AD - especially for IgA aβ2GPI - and a lack of IgG aPS/PT positivity in the AD group. We found no SVBL patient positive for IgA aCL, IgG anti-PE, annexin V, or aβ2GPI domain I., Conclusions: Extra-criteria aPL can improve sensitivity for APS diagnosis in patients with SVBL, especially IgA aβ2GPI and IgG anti-PS/PT antibodies., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest regarding the publication of this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)