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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. [ABSTRACT FROM AUTHOR]

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 The editorial discusses the various celebratory issues that have been published over the years, which contain historical content related to the fields of thrombosis and hemostasis.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]

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]

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]

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]

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]

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. [ABSTRACT FROM AUTHOR]

Summary: Adjuvants, as the name indicates, are adjoined material aimed to assist in functioning as when added to vaccines they are meant to boost the effect and strongly stimulate the immune system. The response of the immune system can be unpredictable, and the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was developed to address possible adverse reactions of an autoimmune and inflammatory type that may be caused by adjuvants. While ASIA, as a syndrome, was coined and defined in 2011; reports describing patients with vague and nonspecific clinical symptoms following vaccinations appeared much earlier. In other words, ASIA came to define, arrange, and unite the variety of symptoms, related to autoimmunity, caused not by the vaccine itself, rather by the adjuvant part of the vaccine such as aluminum, among others. Accordingly, the introduction of ASIA enabled better understanding, proper diagnosis, and early treatment of the disorder. Furthermore, ASIA was shown to be associated with almost all body systems and various rheumatic and autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, and systemic sclerosis. In addition, the correlation between COVID-19 and ASIA was noticed during the pandemic. In this review, we summarized the reported effects of adjuvants and medical literature before and after ASIA was defined, the several ways ASIA can manifest and impact different systems of the body, and the incidences of ASIA during the COVID-19 pandemic. It is important to clarify, that vaccines are among, if not the, most effective means of fighting infectious diseases however, we believe that vaccines manufacturing is not above criticism, particularly when it comes to added substances possessing a risk of side effects. Adjuvants such as aluminum, mineral oils, and silicone are added to vaccines in order to trigger a stronger immune response. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was introduced in 2011 to address nonspecific symptoms and disorders appearing following vaccinations, which in fact were reported by many papers before the introduction of the syndrome. During the pandemic of COVID-19, a correlation between ASIA, COVID-19, and COVID-19 vaccines has been reported. [ABSTRACT FROM AUTHOR]

Extracellular microparticles provide a means of cell-to-cell communication and can promote information exchanges between adjacent or distant cells. Platelets are cell fragments that are derived from megakaryocytes. Their main functions are to stop bleeding, regulate inflammation, and maintain the integrity of blood vessels. When platelets are activated, they can perform related tasks by secreting platelet-derived microparticles that contain lipids, proteins, nucleic acids, and even organelles. There are differences in the circulating platelet levels in many autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid antibody syndrome, and Sjogren's syndrome. In this paper, the latest findings in the research field of platelet-derived microparticles are reviewed, including the potential pathogenesis of platelet-derived microparticles in various types of immune diseases, their potential as related markers, and for monitoring the progress and prognosis of disease treatment are expounded. [ABSTRACT FROM AUTHOR]

Thrombophilia is a group of inherited or acquired coagulation disorders that have been associated with reproductive failure. However, there are still no clear recommendations on whether its inclusion in the initial study of the infertile couple or patients with recurrent implantation failure is necessary. In this discussion paper, based on a SWOT (strengths, weaknesses, opportunities, threats) analysis, the different aspects of the repercussions of thrombophilia screening and treatment in reproduction are evaluated. To avoid possible subjectivity in the analysis and results of this study, researchers followed Oxford criteria for the evaluation of evidence. The results from the evaluation of the reviewed bibliography seem to indicate that, pending new evidence, it would be advisable not to include thrombophilia screening in the initial baseline study of the infertile couple. There is no evidence to support a clear association between thrombophilia and implantation failure or infertility. Thrombophilia testing in this setting may increase cost, with minimal potential benefit and lead to inappropriate use of anticoagulants with possible deleterious adverse effects. Future well-designed studies are needed to assess the possible benefit of anticoagulant therapy in infertile thrombophilic patients with implantation failure. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to explore whether antisense oligonucleotides (ASOs) that reduce LncNR_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. 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. Transfected with ASOs, LncNR_040117 was downregulated in trophoblasts compared with APS-induced RPL patients. And LncNR_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. This study indicated that ASOs that decrease LncNR_040117 expression can reduce apoptosis and enhance the invasion and migration of trophoblasts by regulating the MAPK pathway. [ABSTRACT FROM AUTHOR]

Aortitis is a classic manifestation of large vessel vasculitis. Antiphospholipid syndrome (APS), sometimes known as Hughes syndrome, is an acquired autoimmune disorder that manifests clinically as recurrent venous or arterial thrombosis. Patients with APS may also suffer from various underlying diseases, most frequently systemic lupus erythematosus (SLE). Catastrophic antiphospholipid syndrome (CAPS) is a rare but serious complication of APS characterized by failure of several organs due to diffuse microcirculatory thrombi. Its main manifestations involve the kidneys, lungs, heart and central nervous system, and require early diagnosis and rapid therapeutic management. While APS can affect virtually any blood vessel, aortitis is not a known symptom of APS. We report the case of a 36-year-old patient with APS and SLE who presented with CAPS during pregnancy, with no concomitant SLE flare. The first manifestation of CAPS was aortitis, preceding renal, cardiac and haematological manifestations. The outcome was favourable with combined treatment including corticosteroids, anticoagulants, plasma exchange and rituximab. We then carried out a literature search for papers describing the presence of aortitis in APS and/or SLE. In the cases of aortic involvement identified in the literature, including another case of CAPS, the occurrence of aortitis in SLE, often associated with the presence of antiphospholipid antibodies/APS, suggests that aortitis should be considered as an under-recognized manifestation and potential non-criterion feature of APS. [ABSTRACT FROM AUTHOR]

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]

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by the presence of antiphospholipid antibodies in patients with arterial or venous thrombosis or pregnancy complications. This paper reports a case of a 31-year-old woman who died after she underwent C-section for intrauterine fetal death (IUFD) at the 25th week of gestation. The patient was complaining of pelvic pressure, swelling in the lower limbs, and pain in the groin, one big toe, and both wrists. She had low platelet count, liver abnormalities, and proteinuria. After IUFD, she complained of flank pain and headache. After discharge from the hospital, the patient had constant headaches and 5 days later woke up with hemiplegia. CT scan showed cerebral hemorrhage in the right hemisphere and thrombosis in the left hemisphere. The LA and APS tests were positive. The main cause of death was hemorrhage and infarction in the brain. [ABSTRACT FROM AUTHOR]

The term thrombophilia describes disorders associated with an increased predisposition of developing venous thromboembolism (VTE). It may be acquired, like in those with antiphospholipid syndrome or inherited. The aim of this review was to compare the complications and outcomes of pregnancies in women with inherited thrombophilia between different populations, including the population of our country where the results of the research are scarce. The review of literature included all papers indexed on PubMed and Medline in the last 20 years, with different study design, including other reviews of literature, systematic reviews with meta-analysis and several case-control studies and population-based cohort studies. We aimed to cover as many geographic regions as possible with the aim to show the differences in the different parts of the world and including our country. Our analysis showed that types of thrombophilia differ in different geographic regions. Also, the differences exist between one particular type of thrombophilia in different regions. Nevertheless, no matter what the differences are between prevalence, all authors investigated the association between inherited thrombophilia and poor pregnancy outcome and managed to find some kind of association. The case with our own country is similar. Although we lack in studies with this issue and the design of published studies is not powerful enough, we may conclude that in our samples, women with thrombophilia are in potential risk of several poor pregnancy outcomes. Further and better analyses are necessary to prove this hypothesis not only on the level of study sample but also on general population. Given the fact that thrombophilia certainly affects the pregnancy and its outcome, the urge to perform screening tests in every woman suspected to have this kind of disorder and with respect to differences that exist in different world regions is inevitable. [ABSTRACT FROM AUTHOR]

Background: This paper describes a case of antiphospholipid syndrome-like condition caused by coronavirus disease 2019. The medical community still faces many diagnostic and therapeutic challenges vis-à-vis coronavirus disease 2019. Ultimately, coronavirus disease 2019 is diagnosed on the basis of laboratory and radiological findings. Considering the high rate of mortality due to coagulation abnormalities and thrombosis among coronavirus disease 2019 patients, it is important to pay attention to the differential diagnoses of coronavirus disease 2019 and other diseases following thrombotic events.Case Description: The patient was a 56-year-old Iranian man who underwent coronary artery bypass graft surgery and mitral valve repair. During hospitalization, the patient showed an elevated level of anticardiolipin antibody (immunoglobulin G isotype), antiphospholipid antibodies, and thrombosis in the brachial artery of the left hand, based on which a differential diagnosis of antiphospholipid syndrome was made. However, ultimately, the coronavirus disease 2019 polymerase chain reaction test and computed tomography scan of the lungs showed that the patient had coronavirus disease 2019.Conclusion: According to the few studies performed on coronavirus disease 2019 patients, elevated levels of the isotypes of antiphospholipid antibodies in coronavirus disease 2019 patients create conditions similar to antiphospholipid syndrome, which, in the absence of reliable coronavirus disease 2019 testing, can lead to misdiagnosis and consequently delayed or improper treatment. Therefore, to provide timely and appropriate treatment, it is important to pay attention to differential diagnosis. [ABSTRACT FROM AUTHOR]

Background: Antiphospholipid syndrome (APS) is an acquired pre-thrombotic autoimmune condition, which produces autoantibodies called antiphospholipid antibodies (APL) against phospholipid-binding plasma proteins. The diagnosis of APS requires at least one of Sapporo standard clinical manifestations and one laboratory criteria (persistently medium/high titer anticardiolipin antibodies, and/or medium/high titer anti-β2-glycoprotein I antibodies, and/or a positive lupus anticoagulant test). Gastrointestinal lesions are rarely reported in APS patients. APS cases with recurrent abdominal pain as the first clinical manifestation are even rarer.Case Presentation: This report describes an APS case with recurrent abdominal pain as the first clinical manifestation of antiphospholipid syndrome. The patient has a history of two miscarriages. Computed tomography of the abdomen confirmed mesenteric thrombosis and intestinal obstruction while laboratory tests for serum antiphospholipid and anti-β2-glycoprotein I antibodies were positive. This led to the diagnosis of APS.Conclusions: This paper provides useful information on gastrointestinal manifestations and APS, also including a brief literature review about possible gastrointestinal symptoms of APS. [ABSTRACT FROM AUTHOR]

Objectives: In this paper, we describe the steps followed for the development of a certified reference material for immunoglobulin G antibodies against β2-glycoprotein I (also known as apolipoprotein H). These steps include processing of the material, commutability, the impact of dilution, the appropriate reconstitution conditions, homogeneity and stability during transport and storage. Methods: We analysed 69 clinical samples from patients suffering from antiphospholipid syndrome with several commercial enzyme-linked immunosorbent assays (ELISA) purchased from in vitro diagnostic manufacturers. Results: Analysis of the results indicated that the candidate reference material can be safely freeze-dried, and that the user should carefully follow the reconstitution instructions as small changes in e.g. temperature may have unwanted effects. The statistical analysis of the commutability studies indicated that the analytical response of the reference material upon dilution is similar to that of clinical samples, and that correlation between results may differ from assay to assay. Finally yet importantly, the presented and developed candidate reference material is commutable for most assays tested, homogeneous and stable. Conclusions: Immunoglobulin G antibodies against β2-glycoprotein I are associated with a higher risk of thrombosis and pregnancy complications. Their measurement is essential for the diagnosis and monitoring of antiphospholipid syndrome. These antibodies are detected by specific immunoassays, routinely used in clinical diagnostics, but various of these methods show enormous variability, in part due to the lack of a reference material. [ABSTRACT FROM AUTHOR]

Nephrotic syndrome (NS) can be a symptom of many autoimmune, metabolic, or infectious diseases. Kidney involvement is often observed in the course of diabetes mellitus (DM) and systemic lupus erythematosus (SLE). The development of NS with coexisting SLE and DM generates serious diagnostic problems. In this paper, the authors present diagnostic and therapeutic dilemmas in a patient with long-lasting DM, SLE, and secondary antiphospholipid syndrome, in whom NS symptoms appeared. Histopathological examination of the kidney confirmed the diagnosis of lupus nephritis. Immunosuppressive and anticoagulant drugs were used. The authors demonstrated that the character of morphologic lesions in the kidney biopsy can help in diagnosis, nephropathy classification, and further therapeutic decisions, which are distinct in both diseases. [ABSTRACT FROM AUTHOR]

Objective: The objective of this paper is to assess the prevalence of the main clinical manifestations and laboratory features at disease onset and during the ensuing 10 years of a large cohort of patients with antiphospholipid syndrome (APS) from a single center. Methods: The study included all consecutive APS patients followed longitudinally in our center from 2003 to 2013. Descriptive statistics for demographics, clinical and laboratory features and mortality were performed. Results: A total of 160 patients were included. Most of them, 128 (78.8%), were women and the mean (SD) age at diagnosis was 39.1 (14.0) years. The majority of them, 104 (65.0%), had primary APS, 36 (22.5%) had APS associated with systemic lupus erythematous, and 20 (12.5%) had APS associated with other autoimmune disease. During the study period, thrombotic events occurred in 27 (16.9%) patients, the most common being strokes, nonbacterial thrombotic endocarditis and deep venous thrombosis. Regarding obstetric morbidity, 18 women (14.3%) became pregnant and 90% of pregnancies succeeded in having live births. The most common obstetric complication was early pregnancy loss (15% of pregnancies). Prematurity (11.1% of live births) and intrauterine growth restriction (5.6% of live births) were the most frequent fetal morbidities. Ten (6.3%) patients died and the most frequent causes of death were severe thrombosis, hemorrhage, and cancer. Three (0.9%) cases of catastrophic APS occurred. The survival probability at 10 years was 93.8%. Conclusions: Patients with APS develop significant morbidity and mortality despite current treatment. It is imperative to identify prognostic factors and therapeutic measures to prevent these complications. [ABSTRACT FROM AUTHOR]

An Erratum to this paper has been published: https://doi.org/10.1134/S160767292305006X [ABSTRACT FROM AUTHOR]

An Erratum to this paper has been published: https://doi.org/10.1134/S1607672923050046 [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder marked by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). At the present time, treatment is primarily focused on anticoagulation. However, there is increasing awareness of the mechanisms involved in APS pathogenesis, which has led to the trial of novel therapies targeting those mechanisms. Following a brief review of the etiopathogenesis of and current management strategies in APS, this paper focuses on the evidence for these potential, targeted APS treatments, e.g., hydroxychloroquine, statins, rituximab, belimumab, eculizumab, defibrotide, sirolimus, and peptide therapy. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Lipid profiles of injured and healthy knees' synovial fluids show significant differences. • Osteoporosis changes the SF content and the lipid profile substantially. • An increase in phospholipids over the fractured ones and in the lysophosphatidylcholine levels was observed. • The frictional behavior of the solid bilayer lubricant is dominated by lamellar slippage of bilayers. • The high concentration of PL during inflammation (APS) is of secondary importance in the frictional behavior. Abstract The paper shows that osteoporosis (OA) changes the SF content and the lipid profile substantially. To estimate the implication of the lipid environment in case the articular cartilage (AC) changes, we measured friction coefficient normal samples, with early and late stages of (OA). During joint inflammation and osteoarthritis, enzymatically activated β 2 -Glycoprotein I is transformed into antibody conformation. Our hypothesis about cartilage degradation of PL bilayers by antibodies (β 2 -Glycoprotein I) is considering antiphospholipid syndrome (APS), which was not discussed in the literature before. Deactivated PL molecule has no ability to form bilayers, lamellar phases, and liposomes. The phospholipid content in synovial fluid (SF) during joint inflammation, osteoarthritis, and rheumatoid arthritis is significantly higher (2–3 times) above the normal concentration of PL, and has a poor boundary-lubricating ability is deactivated. [ABSTRACT FROM AUTHOR]

The article introduces various papers published within the issue, including one on thrombosis as a major contributor to global disease burden, another on venous thromboembolism (VTE) in tropical Australia and in indigenous Australians and a paper on antiphospholipid syndrome (APS).

Objective: The objective of this paper is to conduct a systematic review and meta-analysis on the risk of developing elevated antiphospholipid (aPL) antibodies and related thromboembolic and/or pregnancy events following a viral infection. Method: We searched Medline, EMBASE, Web of Science, PubMed ePubs, and Cochrane Central Register of Controlled Trials through June 2016. Independent observational studies of elevated aPL antibodies in patients with a viral infection compared with controls or patients with lupus were included. Results: We analyzed 73 publications for 60 studies. Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) were most commonly reported. Compared with healthy controls, patients with HIV were more likely to develop elevated anticardiolipin (aCL) antibodies (risk ratio (RR) 10.5, 95% confidence interval (CI) 5.6-19.4), as were those with HCV (RR 6.3, 95% CI 3.9-10.1), hepatitis B virus (HBV) (RR 4.2, 95% CI 1.8-9.5), and Epstein-Barr virus (EBV) (RR 10.9 95% CI 5.4-22.2). The only statistically significant increased risk for anti-β2-glycoprotein I (anti-β2-GPI) antibodies was observed in patients with HCV (RR 4.8 95% CI 1.0-22.3). Compared with patients with lupus, patients with HIV were more likely to develop elevated aCL antibodies (RR 1.8, 95% CI 1.3-2.6), and those with EBV, elevated anti-β2-GPI antibodies (RR 2.2, 95% CI 1.3-3.9). Thromboembolic events were most prevalent in patients with elevated aPL antibodies who had HCV (9.1%, 95% CI 3.0-18.1), and HBV (5.9%, 95% CI 2.0-11.9) infections, and pregnancy events were most prevalent in those with parvovirus B19 (16.3%, 95% CI 0.78-45.7). However, compared to virus-infected patients with negative aPL antibodies, the only statistically significant increased risk was observed in those with HCV and positive aPL. Conclusions: Viral infection can increase the risk of developing elevated aPL antibodies and associated thromboembolic events. Results are contingent on the reported information. [ABSTRACT FROM AUTHOR]

Objectives This paper aims to assess in a retrospective fashion the clinical and laboratory features, severity and outcome of juvenile systemic lupus erythematosus (jSLE) from a referral center in Turkey. Methods We have included all jSLE patients (n = 92) diagnosed according to the revised American College of Rheumatology 1997 criteria between January 2004 and January 2017. Results The most prevalent clinical feature in our cohort was mucocutaneous manifestations (97.8%), followed by constitutional (81.5%), hematological (59.8%) and musculoskeletal manifestations (56.5%). Renal involvement was observed in 38% (n = 35) of the patients, whereas biopsy-proven lupus nephritis was detected in 29.3% (n = 27) of the cohort. Neurologic involvement was seen in 15 (16.3%) individuals. Among the patients positive for anticardiolipin IgM and/or IgG (n = 11, 12%), only three developed antiphospholipid antibody syndrome. The mean SLEDAI-2K scores at disease onset (10.5 ± 4.8) showed a substantial decrease at last visit (4.3 ± 4.6). One-quarter of the patients (26.1%, n = 24) had damage according to the PedSDI criteria with a mean score of 0.45 ± 1.0 (range 0–7). When the PedSDI damage items were evaluated individually, growth failure was the most frequent damage criterion (n = 6), followed by seizure (n = 5). Two patients died during the designated study period of end-stage renal disease. The five-year and 10-year survival rate of our cohort was 100% and 94.4%, respectively. Conclusions Given the lower frequency of nephritis and central nervous system disease and lower basal disease activity and damage scores, we could conclude that children with jSLE in Turkey have a more favorable course compared to Asian and African American children, as expected from Caucasian ethnicity. [ABSTRACT FROM AUTHOR]

The major treatment issues in Antiphospholipid Syndrome (APS) include the the prevention of first thrombosis, the treatment of acute thromboembolic manifestations, the choice of anticoagulation, the duration of anticoagulation and secondary thrombosis prevention. Anticoagulation should individualized to the patient and clinical setting. Clasical anti vitamin K antagonists, warfarin and acenocumoral, carry some risks and disadvantages. Direct thrombin inhibitor and direct anti-Xa inhibitors are currently available and were approved for the prevention of stroke and systemic embolism in patients with atrial fibrillation, for the treatment of deep vein thrombosis (DVT) and for the prevention of recurrent DVT and pulmonary embolism. Besides many case series reports, there are ongoing clinical trials testing their efficiency and safety in patients with APS. In this paper we reviewed the advantages, risks and disadvantages for the use of direct oral anticoagulants in this category of patients. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibody syndrome (APS) is an autoimmune acquired thrombophilia characterized by recurrent thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). APS can be primary, if it occurs in the absence of any underlying disease, or secondary, if it is associated with another autoimmune disorder, most commonly systemic lupus erythematosus. The exact pathogenetic mechanism of APS is unknown, but different, not mutually exclusive, models have been proposed to explain how anti-PL autoantibodies might lead to thrombosis and pregnancy morbidity. Diagnosis of APS requires that a patient has both a clinical manifestation (arterial or venous thrombosis and/or pregnancy morbidity) and persistently positive aPL, but the clinical spectrum of the disease encompasses additional manifestations which may affect every organ and cannot be explained exclusively by a prothrombotic state. Treatment for aPL-positive patients is based on the patient's clinical status, presence of an underlying autoimmune disease, and history of thrombotic events. In case of aPL positivity without previous thrombotic events, the treatment is mainly focused on reduction of additional vascular risk factors, while treatment of patients with definite APS is based on long-term anticoagulation. Pregnancy complications are usually managed with low-dose aspirin in association with low molecular weight heparin. Refractory forms of APS could benefit from adding hydroxychloroquine and/or intravenous immunoglobulin to anticoagulation therapy. Promising novel treatments include anti-B cell monoclonal antibodies, new-generation anticoagulants, and complement cascade inhibitors. The objective of this review paper is to summarize the recent literature on APS from pathogenesis to current therapeutic options. [ABSTRACT FROM AUTHOR]

Cognitive disorders have frequently been described in the field of antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Nevertheless, the relationship between those disorders and antiphospholipid antibodies (aPL) remains unclear and seems to involve various mechanisms. Overlap with systemic lupus erythematosus, the small sample size of studies, and discrepancies in antiphospholipid antibodies and cognitive impairment determinations complicate analyses of the literature data. In this paper, we summarize current knowledge on epidemiologic, clinical data, imaging findings and treatment of cognitive dysfunction associated with aPL. We separately analyzed data on aPL-positive carriers without history of clinical feature of APS, APS patients without overlaps autoimmune disease, and SLE-associated aPL patients. [ABSTRACT FROM AUTHOR]

The scope of clinical and laboratory manifestations of the antiphospholipid syndrome (APS) has increased dramatically since its discovery in 1983, where any organ system can be involved. Musculoskeletal complications are consistently reported in APS patients, not only causing morbidity and mortality, but also affecting their quality of life. We reviewed all English papers on APS involvement in the musculoskeletal system using Google Scholar and Pubmed; all reports are summarized in a table in this review. The spectrum of manifestations includes arthralgia/arthritis, avascular necrosis of bone, bone marrow necrosis, complex regional pain syndrome type-1, muscle infarction, non-traumatic fractures, and osteoporosis. Some of these manifestations were reported in good quality studies, some of which showed an association between aPL-positivity and the occurrence of these manifestations, while others were merely described in case reports. [ABSTRACT FROM AUTHOR]

Objective The objective of this paper is to determine which kinds of assays for antiphospholipid antibodies (aPL) should be tested for clinical practice for patients with recurrent pregnancy loss (RPL). Materials and methods We studied 560 patients with a history of RPL prospectively. We determined the obstetric significance of 11 commercially available tested assays for lupus anticoagulant (LA)-aPTT StaClot, phosphatidylserine-dependent antiprothrombin (aPS/PT) IgG, IgM, classical cardiolipin (CL) IgG, IgM, CL IgG, IgM, IgA, and β2glycoprotein I (β2GPI) IgG, IgM, IgA Phadia. Obstetric significance was defined as the potential for anticoagulant therapy to improve the subsequent live birth rate, or a difference in the live birth rate between positive and negative untreated cases. Results The LA-aPTT StaClot assay and aPS/PT IgG assay, but not CL IgG, were found to have obstetric significance. Our conventional tests covered positive cases with the aPS/PT IgM and classical CL IgG assays. The results of the LA-aPTT StaClot, LA-aPTT and LA-RVVT assays showed different distributions, although strong or moderate correlation was observed. Conclusion LA-aPTT StaClot and aPS/PT IgG might be suitable for use in routine practice for patients with RPL. Each test for aPL should be ascertained for obstetric significance, because similar assays may have different outcomes. [ABSTRACT FROM AUTHOR]

Background: In this paper we describe a novel method to achieve high yield bacterial expression of a small protein domain with considerable therapeutic potential; Domain I of Beta-2-glycoprotein I (β2GPI). β2GPI is intrinsic to the pathological progression of the Antiphospholipid Syndrome (APS). Patients develop autoantibodies targeting an epitope located on the N-terminal Domain I of β2GPI rendering this domain of interest as a possible therapeutic. Results: This new method of production of Domain I of β2GPI has increased the production yield by ~20 fold compared to previous methods in E.coli. This largely scalable, partially automated method produces 50-75 mg of pure, folded, active Domain I of β2GPI per litre of expression media. Conclusion: The application of this method may enable production of Domain I on sufficient scale to allow its use as a therapeutic. [ABSTRACT FROM AUTHOR]

Introduction In antiphospholipid syndrome (APS), certain principal manifestations are associated with a worse prognosis and organ damage. Objective The objective of this paper is to describe the development and initial content, criterion and construct validity of a disease-specific cumulative damage index in patients with thrombotic APS (DIAPS). Methods Through expert panel agreement, 47 items were considered to reflect damage in APS. This preliminary version of the DIAPS was submitted to four local and international clinical and research experts in APS who ranked each item according to severity. A Delphi exercise resulted in a final 37 item instrument. In the second phase, a cross-sectional study was conducted applying the DIAPS in patients included in a multicenter electronic registry of patients with APS. Quality of life related to health status was evaluated with the EuroQol for construct validation. An α Cronbach and correlation with the EuroQol scale were calculated with SPSS 20.0 (p < 0.05). Results We evaluated the DIAPS in 156 patients, 77% female, with a mean age at diagnosis 34.7 ± 5.5 years. A total of 69% had primary APS. Common comorbidities included obesity, depression and dyslipidemia. The most frequent manifestations resulting in sequelae were deep venous thrombosis and ischemic stroke. Blindness, retinal occlusive vessel disease, myocardial infarction, cardiac valve requiring replacement, mesenteric thrombosis, and renal insufficiency also occurred. Homogeneity: α Cronbach 0.619. DIAPS items correlated with EuroQol domains with the exception of pulmonary, renal, gastrointestinal, and endocrine systems. Conclusion This study demonstrates content, criterion and construct validity of a new physician-reported instrument to assess the DIAPS. In addition, the DIAPS correlated with the EuroQol. [ABSTRACT FROM AUTHOR]

In a previous systematic literature search, we demonstrated that the frequencies of antiphospholipid antibodies (aPL) in general-population patients with pregnancy morbidity (PM), deep vein thrombosis (DVT), myocardial infarction (MI), and stroke (ST) are 6%, 10%, 11%, and 14%. To determine the association between aPL and clinical outcomes, we conducted a follow-up analysis of the 120 studies included in the original paper. Based on the analysis of 81 studies, a significant difference in the frequency of aPL criteria tests between patients and controls emerged considering all the outcomes together (10% versus 3%). In particular, a significant difference was reported for overall PM, pregnancy loss (PrL), late PrL, severe preeclampsia (PEC), ST, MI, and DVT. No difference emerged for early PrL, intrauterine growth restriction (IUGR), PEC, eclampsia (EC), and HELLP. A positive association was found in more than half of the studies for overall PrL, severe PEC, HELLP, ST, MI, and DVT and in less than half for early and late PrL, PEC, EC, and IUGR. The positive association between aPL and clinical outcomes included in the antiphospholipid syndrome classification criteria is not supported by every study, being particularly inconsistent for early PL, IUGR, PEC, EC, and HELLP. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) and antiphospholipid syndrome (APS) share common clinical, laboratory and radiological features. We reviewed all the English papers on MS and APS published in the literature from 1965 to 2014 using PubMed and Google Scholar. We found that APS can mimic antiphospholipid antibodies (aPL)-positive MS in many ways in its clinical presentation. Nevertheless, APS diagnosis, clinical manifestations and management differ from those of MS. aPL were found in MS patients with titers ranging from 2% to 88%. The distribution and volume of lesions on magnetic resonance imaging (MRI) may help to differentiate MS from primary APS. In addition, atypical MS presentation can guide physicians toward an alternative diagnosis, especially when features of thrombosis and/or history of connective tissue disease are present. In that case, an anticoagulation trial could be worthwhile. [ABSTRACT FROM AUTHOR]

Background: Agenesis of the inferior vena cava (AIVC) is a rare disorder that, when combined with co-morbid hypercoagulable disease such as antiphospholipid antibody syndrome (APAS), increases the risk of chronic deep vein thrombosis (DVT). We report a 33-year-old female with a past medical history of recurrent DVTs and antiphospholipid antibody syndrome (APAS) who at the age of 33, was incidentally found to have AIVC while assessing clot burden, which likely contributed to her recurrent DVT episodes earlier in life. Management: The combination of AIVC and antiphospholipid antibody syndrome is rare and can lead to recurrent DVTs in young patients. Prolonged anticoagulation is the preferred treatment when used in conjunction with the prescription of compression stockings, modification of risk factors, and treatment of further complications. In this paper we provide a case discussion and up-to-date information on diagnosis and management of a patient with both AIVC and APAS. [ABSTRACT FROM AUTHOR]

Background: Agenesis of the inferior vena cava (AIVC) is a rare disorder that, when combined with co-morbid hypercoagulable disease such as antiphospholipid antibody syndrome (APAS), increases the risk of chronic deep vein thrombosis (DVT). We report a 33-year-old female with a past medical history of recurrent DVTs and antiphospholipid antibody syndrome (APAS) who at the age of 33, was incidentally found to have AIVC while assessing clot burden, which likely contributed to her recurrent DVT episodes earlier in life. Management: The combination of AIVC and antiphospholipid antibody syndrome is rare and can lead to recurrent DVTs in young patients. Prolonged anticoagulation is the preferred treatment when used in conjunction with the prescription of compression stockings, modification of risk factors, and treatment of further complications. In this paper we provide a case discussion and up-to-date information on diagnosis and management of a patient with both AIVC and APAS. [ABSTRACT FROM AUTHOR]

Sir, I read with great interest the study by Sato et al. comparing factor Xa inhibitors for preventing recurrent thrombosis in heterogeneous patients with antiphospholipid syndrome (APS) with warfarin in the same group of patients and with warfarin in the control group.[1] Results of the study are reported for all three factor Xa inhibitors as a single entity. Because of that, a table with information about the factor Xa inhibitor used, time to event and aPL profile of every Xa inhibitor used would be valuable, more so because data on edoxaban use in APS patients are scarce and not easy to find in existing papers, and they are not presented in this study either. [Extracted from the article]

Recently, we read with great interest the papers by Kwak-Kim et al from "The 39th Annual Meeting of the American Society for Reproductive Immunology" (12-15 June 2019, Grand Rapids, Michigan, USA).[[1]] The authors investigated reproductive outcomes of women with recurrent pregnancy loss (RPL) and repeated implantation failure (RIF) who received intravenous immunoglobulin G (IVIg) infusion. The most commonly reported allergies were similar before and after IVIg treatment reaching a prevalence similar to general population estimates. Taken together, these indirect data clearly support the high success rate of IVIg-treated pregnancy in RPL women with APS or immunological disorders [[3], [6]] and highlight that RPL seems most likely associated with the occurrence of thyroid diseases.[[5], [8], [10]] Interestingly, for the first time, our data provide overall evidence for a successful very long-term outcome for both the IVIg-treated mothers and their living children who were in utero exposed to IVIg. [Extracted from the article]

Background: The role of maternal exposures and conditions in the origin of childhood cancer has been a subject of growing interest, but current evidence is inconclusive. Case presentation: We present a case detected in a multicenter case-control study evaluating the association between parental risk factors and childhood acute lymphoblastic leukemia (ALL). The patient is a Colombian girl who was diagnosed with ALL-L1 when she was 2 years old. Her mother had been diagnosed with antiphospholipid syndrome before pregnancy and had also been treated with subcutaneous injections of heparin. Other potentially relevant maternal and patient exposures are also reported in this paper. Conclusion: We hypothesize that the maternal autoimmune disease could be a contributor in the causality network of the daughter's leukemia. However, the role of other exposures cannot be excluded. [ABSTRACT FROM AUTHOR]

Evidence from basic science studies supports a causative relationship between antiphospholipid antibodies (aPL) and recurrent early miscarriage (REM) (prior to 10 weeks of gestation). However, human studies have not consistently found a relationship between aPL and REM. Members of the Obstetric Task Force of the 14th International Congress on Antiphospholipid Antibodies performed a literature review of the association of aPL and REM and searched for clinical trials in women with REM who tested positive for aPL. Of the 46 studies that investigated the relationship between aPL and REM, 27 found a positive association, seven found no association, and the remaining 12 papers could not report an association (lack of control group). The main identified problems for such conflicting results were varying definitions of REM (two or three abortions, not necessarily consecutive; different gestational age at which pregnancy losses occurred); analysis of patients with previous fetal death (>10 weeks) in the same group of REM; and different definitions of “positive aPL” (cutoffs not following international recommendations; small number of studies confirmed persistence of positive aPL after six to 12 weeks). The 10 identified randomized trials with proposed treatments for women with REM who test positive for aPL also had heterogeneous inclusion criteria, with only one trial limited to subjects who would meet the current criteria for antiphospholipid syndrome (APS) by both clinical and laboratory criteria. Against this background, we conclude that the association between REM and aPL remains inconclusive and that the findings of treatment trials are at best inconsistent and at worst misleading. More convincing data are critically needed. Studies that identify, or at least stratify, according to international consensus criteria and include standardized core laboratory testing results are crucial if we are to establish an evidence-based association between aPL and REM and treatment recommendations. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

The article discusses a research paper on antiphospholipid (APS) syndrome. It references the study "Antiphospholipid Antibodies Induce Thrombosis by PP2A Activation Via apoER2-Dab2-SHC1 Complex Formation in Endothelium," by A. Sacharidou et al., published within the issue. It tackles the characterization of APS syndrome and the significant role of endothelial cells in the thrombotic risk induced by anti-β2 glycoprotein I antibodies.

Background: Rare diseases are a global public health priority. Though each disease is rare, when taken together the thousands of known rare diseases cause significant morbidity and mortality, impact quality of life, and confer a social and economic burden on families and communities. These conditions are, by their nature, encountered very infrequently by individual clinicians, who may feel unprepared to address their diagnosis and treatment. Clinical practice guidelines are necessary to support clinical and policy decisions. However, creating guidelines for rare diseases presents specific challenges, including a paucity of high certainty evidence to inform panel recommendations.Methods: This paper draws from the authors' experience in the development of clinical practice guidelines for three rare diseases: hemophilia, sickle cell disease, and catastrophic antiphospholipid syndrome.Results: We have summarized a number of strategies for eliciting and synthesizing evidence that are compatible with the rigorous, internationally accepted standards for guideline development set out by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. These strategies include: use of pre-existing and ad hoc qualitative research, use of systematic observation forms, use of registry data, and thoughtful use of indirect evidence. Their use in three real guideline development efforts, as well as their theoretical underpinnings, are discussed. Avenues for future research to improve clinical practice guideline creation for rare diseases - and any disease affected by a relative lack of evidence - are also identified.Conclusions: Rigorous clinical practice guidelines are needed to improve the care of the millions of people worldwide who suffer from rare diseases. Innovative evidence elicitation and synthesis methods will benefit not only the rare disease community, but also individuals with common diseases who have rare presentations, suffer rare complications, or require nascent therapies. Further refinement and improved uptake of these innovative methods should lead to higher quality clinical practice guidelines in rare diseases. [ABSTRACT FROM AUTHOR]

Background: Antiphospholipid syndrome is an autoimmune disorder characterized by the presence of antiphospholipid antibodies and commonly presents with vascular thromboembolic phenomena, thrombocytopenia, and obstetric complications. Antiphospholipid syndrome can be classified as either primary or secondary to other connective tissue diseases. Dermatologic manifestations are common; however, non-vasculitic skin ulceration is an uncommon manifestation of antiphospholipid syndrome with limited treatment options.Case Presentation: In this paper we report the case of a 58-year-old white woman who developed necrotic abdominal wall ulcers 27 years after a diagnosis of secondary antiphospholipid syndrome associated with systemic lupus erythematosus. The ulcers developed despite our patient being on therapeutic anticoagulation with warfarin and were resistant to further increases in the intensity of anticoagulation. Management was further complicated due to reluctance on the part of our patient to switch over to injectable heparin.Conclusions: This case highlights a rare late dermatologic presentation of antiphospholipid syndrome, which responded poorly to conventional anticoagulation with warfarin. Current management is limited to experimental therapies and the role of newer anticoagulants is still unknown. [ABSTRACT FROM AUTHOR]

High titer of anti-β2-glycoprotein I antibodies (anti-β2GPI Ab) plays a pathogenic role in antiphospholipid syndrome (APS). Numerous studies have focused on the pathological mechanism in APS; however, little attention is paid to the immune mechanism of production of anti-β2GPI antibodies in APS. Our previous study demonstrated that Toll-like receptor 4 (TLR4) plays a vital role in the maturation of bone marrow-derived dendritic cells (BMDCs) from the mice immunized with human β2-glycoprotein I (β2GPI). TLR4 is required for the activation of B cells and the production of autoantibody in mice treated with β2GPI. However, TLR4 provides a third signal for B cell activation and then promotes B cells better receiving signals from both B cell antigen receptor (BCR) and CD40, thus promoting B cell activation, surface molecules expression, anti-β2GPI Ab production, and cytokines secretion and making B cell functioning like an antigen presenting cell (APC). At the same time, TLR4 also promotes B cells producing antibodies by upregulating the expression of B-cell activating factor (BAFF). In this paper, we aim to review the functions of TLR4 in B cell immune response and antibody production in autoimmune disease APS and try to find a new way for the prevention and treatment of APS. [ABSTRACT FROM AUTHOR]