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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]

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]

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]

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

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

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]

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

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

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

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]

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]

Classification criteria for antiphospholipid syndrome (APS) require IgG or IgM isotypes of the anticardiolipin (aCL) antibodies, anti-β2 glycoprotein I (anti-β2GPI) antibodies, and/or the lupus anticoagulant (LA) to satisfy the laboratory disease definition. Over the past 20 years, non-criteria antiphospholipid antibodies (aPL) directed to other proteins of the coagulation cascade (i.e. prothrombin and/or phosphatidylserine–prothrombin complex) or to some domains of β2GPI have been proposed. This task force concentrated and reviewed the literature on data including aPS/PT, antibodies to domain 4/5 of β2GPI and the newly described antibodies to protein/HLA-DR complex. In addition, we discussed testing of LA in the 'new' oral anticoagulants' era and the value of triple positivity in the risk assessment of aPL. The conclusions were presented at a special session during the 16th International Congress on aPL, Manchester, UK, September 2019. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease that primarily affects women of childbearing-age. Antiphospholipid syndrome (APS) is a systemic autoimmune disorder defined by the occurrence of venous and arterial thrombosis, often multiple, and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). Recently, the long-term outcome of children born to patients with lupus and APS has become a major topic of interest both to patients and physicians. One of the major problems related to maternal disease is preterm delivery with all the consequences that this condition may bring. Prematurity may also be due to the presence of aPL; however, aPL do not generally display any thrombotic potential on neonates. Another complication may be neonatal lupus (NL), mediated by the presence of maternal antibodies (anti-Ro/SSA and anti-La/SSB). In addition, behaviour and neuropsychological outcomes have also been a matter of interest, but there are currently few data available. Beyond the biological influence of both maternal disease and autoimmune background, it is important to focus on the possible influence of maternal chronic illness on the neuropsychological development of her children. Whether aPL exposure could have a direct effect on brain development is still being debated. In children of mothers with APS, language delays have been noted and learning disabilities were described with a higher rate than the general age-school population. Several studies were performed on children born to lupus mothers: even if maternal lupus does not seem to impair intelligence levels, it may increase the occurrence of learning disabilities and particularly dyslexia in male children. To the best of our knowledge, no studies are available on the long-term outcome of children born to mothers with lupus or APS and particularly regarding the development of autoimmune diseases. Nevertheless, common experience of experts in the field is that these children do not show a significantly increased risk of displaying the same autoimmune disease as their mothers. The purpose of this paper is to answer the frequently asked questions of patients with lupus and APS who desire to become mothers, based on the little information available. [ABSTRACT FROM PUBLISHER]

Renal artery stenosis is the narrowing of the renal artery which causes hypertension and atrophy of the affected kidney, ultimately leading to renal failure if not treated and most often caused by atherosclerosis or fibromuscular dysplasia. Recently, renal artery stenosis has also been documented in patients with the antiphospholipid syndrome and in very few cases with myeloproliferative disease. In this paper, we describe a 31-year-old female with a history of gangrene affecting the toes with severe hypertension (200/110 mmHg), whose investigations revealed a combination of renal artery stenosis, primary antiphospholipid syndrome and polycythaemia vera. [ABSTRACT FROM PUBLISHER]

Antiphospholipid syndrome (APS) is a multisystem autoimmune condition characterized by vascular thromboses and/or pregnancy loss associated with persistently positive antiphospholipid antibodies (aPL). Catastrophic APS (CAPS) is the most severe form of APS with multiple organ involvement developing over a short period of time, usually associated with microthrombosis. ‘Definite’ and ‘probable’ CAPS have been defined based on the preliminary classification criteria; however, in a real-world setting, aPL-positive patients with multiple organ thromboses and/or thrombotic microangiopathies exist who do not fulfill these criteria. Previous APS diagnosis and/or persistent clinically significant aPL positivity is of great importance for the CAPS diagnosis; however, almost half of the patients who develop CAPS do not have a history of aPL positivity. The purpose of this paper is to summarize the diagnostic challenges and the recently updated diagnostic algorithms for CAPS providing a ‘step-by-step’ approach for clinicians (and researchers) in the assessment of patients with multiple organ thromboses. [ABSTRACT FROM PUBLISHER]

The discovery of antiphospholipid antibodies (aPL) positivity in individuals who have never experienced thrombosis or pregnancy complications is not a rare event, and is one of the unresolved issues in the field of antiphospholipid syndrome (APS). This paper focuses on primary prophylaxis for thrombotic events in aPL carriers. In our view, patients with high risk aPL profiles and/or other cardiovascular risk factors, concomitant diagnosis of systemic lupus erythematosus (SLE) and patients with an history of obstetric APS (OAPS) should be offered thromboprophylaxis. Chronic thromboprophylaxis with low-dose aspirin and hydroxychloroquine in aPL positive SLE patients should be prescribed both to prevent thrombosis and to avoid early organ damage. [ABSTRACT FROM AUTHOR]

One of the greatest enigmas in thrombosis research is the observation that one can diagnose a person with a thrombotic risk with a prolongation of the clotting time. Our textbooks have taught us that prolongation of clotting correlates with a tendency to bleed. To confuse our textbook knowledge further, the same patients often have a prolonged bleeding time, a diagnostic test to detect a dysfunction in primary haemostasis. In this paper we critically review the literature that tries to explain the contradiction that exists between in-vitro diagnostic tests and the observed clinical manifestations and discuss our current opinion on how antiphospholipid antibodies can disturb the haemostatic balance. [ABSTRACT FROM AUTHOR]

The main objective of these meetings is to promote international collaboration in various clinical and research projects. This paper is the summary of the 2007 Ljubljana meeting, and offers an overview of the proposed projects. The technical and methodological details of the projects will be published on the forum's web site (http://www.med.ub.es/MIMMUN/FORUM/STUDIES. HTM). [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]

The heart lesions of rheumatic fever and the heart involvement in antiphospholipid syndrome (APS), have different clinical pictures. Yet, there are several common characteristics linking both diseases: 1) central nervous system (CNS) and heart involvement; 2) molecular mimicry between the a pathogen and the origin of the disease; 3) cross reacting antibodies between the pathogen and self molecules; 4) endothelial cell activation in the 'crime-area' i.e., the valves; 5) some of the patients with RF have circulating antiphospholipid antibodies, while APS may be associated with streptococcal infection; and 6) recently, a cross-reactivity between antibodies directed to the streptococcal M-protein and its synthetic derivative in rheumatic fever (RF) and antibodies derived from APS patients targeting the beta-2-glycoprotein-I (β2GPI) and a β2GPI related synthetic peptide. In the current paper, we summarize the possible links between the heart involvement in RF and APS. [ABSTRACT FROM AUTHOR]

Some cases of reproductive failure with autoimmune background are characterized by the involvement of autoantibodies. This occurs mainly in patients having systemic lupus erythematosus or antiphospholipid syndrome. The autoantibodies associated with reproductive failure include: a) antibodies which directly bind phospholipid (e.g., cardiolipin, phosphatidylserine, phosphatidylethanolamine); b) antiphospholipid Abs which bind the phospholipid via phospholipid-binding glycoproteins such as β2glycoprotein-I, annexin V and prothrombin; c) autoantibodies directed to laminin-I, actin, thromboplastin, the corpus luteum, prolactin, poly (ADP-ribose), thyroglobulin and mitochondrial antibodies of the M5 type. This paper will focus on the association of antiphosphatidylserine autoantibodies and reproductive failure. Future studies are likely to help to identify peptides resembling the epitope specificities associated with the specific clinical manifestations. [ABSTRACT FROM AUTHOR]

The objective of this paper is to investigate the long-term outcome of primary antiphospholipid syndrome (APS) in the paediatric age. The features of unselected patients with primary APS who had disease onset before the age of 16 years were retrospectively analysed in three Italian referral centres. Clinical and laboratory manifestations were assessed to establish whether, at the end of follow-up, the final diagnosis was still primary APS or whether they had developed definite SLE or lupus-like syndrome. Fourteen patients, nine boys and five-girls, who had the presenting clinical manifestation of APS between three and 13 years of age (median nine years) and were followed for two to 16 years (median six years). Six patients presented with deep vein thrombosis, five with cerebral stroke, two with peripheral artery occlusion and one with myocardial infarction. During follow-up, four patients had one or more recurrences of vascular thrombosis. At last observation, 10 patients could still be classified as having primary APS, two had developed SLE, one lupus-like syndrome and one Hodgkin's lymphoma. In conclusion; our analysis suggests that some children who present with the features of primary APS may progress to develop SLE or lupus-like syndrome. [ABSTRACT FROM AUTHOR]

Antiaggregant and anticoagulant drugs are essential in the management of the manifestations due to antiphospholipid syndrome (APS) in patients with primary Hughes' syndrome or systemic lupus erythematosus. Coumadin derivatives (warfarin and acenocumarol), heparin and aspirin are used for secondary thromboprophylaxis and treatment of recurrent miscarriage. The available evidence for each indication is reviewed in this paper. There is still debate regarding the optimal intensity of oral anticoagulation, the best drug combination for pregnancy failure in APS and the management of asymptomatic patients with antiphospholipid antibodies. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to describe clinical and biological characteristics and thrombotic relapses of patients diagnosed with antiphospholipid syndrome (APS) after the age of 65 years, in comparison with patients diagnosed with APS before 65. Methods: This retrospective multicenter study was performed to 2005 from 2017 and included patients diagnosed with APS after the age of 65 years, in accordance with Sydney criteria. We compared these patients with APS patients diagnosed before the age of 65 years, and with control thrombotic patients older than 65 years. Results: Fifty-eight APS patients over the age of 65 years were compared to 127 APS patients aged less than 65 and to 58 controls. In elderly APS versus younger APS, there was a male predominance (58.6% vs 36.2% p =.001); myocardial infarction and lower limb deep vein thrombosis (LLDVT) were more frequent in elderly, respectively, 12.1% versus 1.6% (p =.005), and 44.8% versus 29.9% (p =.048). Anticardiolipin antibody (aCL) IgM was more frequently found in old patients compared to younger patients (33.9% vs 18.1%, p =.02), contrary to lupus anticoagulant (LAC) (52.8% vs 66.9%, p =.02). Older patients were more often diagnosed with single positive APS (82.8% vs 59.8% p =.002). The thrombotic relapse free survival was lower in elderly APS patients (p =.044) compared to younger APS. Elderly APS patients had more recurrent arterial and venous thrombosis (p =.03) and had poorer overall survival (p =.004) than elderly controls. Conclusion: In this study, APS was different in patients aged more than 65 years, with a male predominance and more myocardial infarctions and LLDVT at diagnosis. Single antiphopholipid positivity and aCL IgM were more frequent in older patients. Older patient with APS had more thrombotic recurrence during follow-up. Compared to elderly controls, elderly APS patients had more thrombosis recurrences and poorer survival. [ABSTRACT FROM AUTHOR]

Background: Livedo is a well-known skin condition in patients with systemic lupus erythematosus (SLE) which correspond to small vessels involvement. The influence of antiphospholipid antibodies (aPL) on the occurrence of livedo is controversial. The aim of our study was to estimate the risk of livedo associated with aPL in patients with SLE. Methods: We conducted a systematic review and meta-analysis of the literature from 1977 to 2021 to estimate the risk of livedo in SLE patients according to different aPL profiles. Data sources were PubMed, Embase, Cochrane Library, hand search, and reference lists of studies. Studies were selected if they included SLE patients with descriptions of the exposure to aPL and the outcome (livedo). Two independent investigators assessed study eligibility, quality, and extracted patient characteristics from each study as well as exposure (aPL) and outcome (livedo). Risk estimates were pooled using random effects models and sensitivity analyses. For all stages of the meta-analysis, we followed the PRISMA guidelines. PROSPERO registration number: CRD42015027377. Results: Of the 2,355 articles identified, 27 were included with a total of 4,810 SLE patients. The frequency of livedo was 25.5% in aPL-positive patients and 13.3% in aPL-negative patients. The overall Odds Ratio (OR) for livedo in aPL-positive patients compared to aPL-negative patients was 2.91 (95% CI; 2.17–3.90). The risk of livedo was significantly increased for most of aPL subtypes, including lupus anticoagulant (LA) (OR = 4.45 [95% CI; 2.21–8.94]), IgG anticardiolipin (OR = 3.95 [95% CI; 2.34–6.65]), and IgG anti-β2-glycoprotein 1 (OR = 3.49 [95% CI; 1.68–7.27]). Conclusions: We demonstrated in this meta-analysis an excess risk of livedo in aPL-positive SLE patients compared to aPL-negative patients. For daily practice, in patients with SLE, livedo associated with aPL could correspond to a peculiar group of patients with small vessel disease. Livedo could be a good candidate for inclusion in future classification criteria for antiphospholipid syndrome. [ABSTRACT FROM AUTHOR]

Conventional therapeutic plasma exchange (TPE) is aimed at removing pathological agents from circulation using a medical device which separates out plasma from other components of blood. Usually, 1.0 to 1.5 plasma volumes are removed and replaced with a replacement solution. There is strong clinical evidence for the effectiveness of TPE in a wide spectrum of diseases, such as thrombotic thrombocytopenic purpura, severe acute inflammatory demyelinating polyneuropathy, and Guillain-Barré syndrome, among others. However, therapeutic approaches using lower plasma exchange volumes (LVPE) suggest some degree of effectiveness in a number of pathological conditions, although generally with low level of clinical evidence: hematology disorders (autoimmune hemolytic anemia), neuroimmunological diseases (Guillain-Barré syndrome, neuromyelitis optica, myasthenia gravis, multiple sclerosis), pulmonary disorders, liver failure, dermatology (pemphigus) and metabolic diseases (porphyria, cholesterol). Further or newer studies are needed to confirm LVPE as an alternative to TPE for such groups of pathologies. While plasma volume removed for TPE ranges 3-4.5 L per procedure, for LVPE ranges from 350 mL to 2 L (frequency and duration vary depending on the pathology treated). In the case of Alzheimer's disease (AD), the AMBAR trial recently investigated a combined sequence of intensive TPE with human albumin replacement followed by a maintenance phase LVPE (650-880 mL of plasma removed, similar to a plasma donation). The treatment slowed the decline or stabilized the disease symptoms. The AMBAR approach could justify investigating the use of LVPE in chronic conditions where plasma exchange strategies have proven successful. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in patients with antiphospholipid syndrome (APS). Methods: We performed a literature search using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. We also performed a meta-analysis of randomized controlled trials (RCTs) investigating the effectiveness and safety of DOACs versus warfarin in patients with APS. Results: Five RCTs involving 648 patients with APS (330 in DOAC-treated and 318 in control groups) were included in the meta-analysis. Among the patients included in the analysis, 29 (8.8%) patients experienced recurrent thrombosis in the DOAC treatment group, and 10 patients (3.1%) had thrombosis recurrence in the warfarin treatment group, resulting in a higher incidence in DOAC-treated than in the warfarin-treated groups [odds ratio (OR) = 2.163, 95% CI = 0.985–4.748, p = 0.055]. Incidence of arterial thrombosis was significantly higher in DOAC-treated patients than in warfarin-treated patients (OR = 5.168, 95% CI = 1.567–17.04, p = 0.007). Stroke and thrombosis occurrences were significantly higher in the triple positivity group than in the warfarin therapy group (OR = 12.03, 95% CI = 2.249–64.36, p = 0.004; OR = 2.940, 95% CI = 1.016–8.504, p = 0.047). However, venous thrombosis occurrences did not differ significantly between the DOAC-treated and warfarin-treated groups. There were no significant differences between the DOAC and warfarin groups in terms of any bleeding, major bleeding, minor bleeding, and all-cause mortality. Conclusion: DOACs were associated with higher rates of arterial thrombosis than warfarin in patients with APS, especially in the triple-positive group. However, a higher risk of recurrent venous thrombosis was not found in APS patients treated with DOACs compared to those treated with warfarin. [ABSTRACT FROM AUTHOR]

Objectives Health-related quality of life (HRQoL) has not been fully explored in antiphospholipid syndrome (APS); therefore, we compared HRQoL between APS patients and the general population and assessed the impact of thromboembolic history. Methods HRQoL was measured in a multicentre cohort study by the Medical Outcomes Study Short-Form 36 (MOS-SF-36) questionnaire. HRQoL scores were compared to the French general population norms. Factors significantly associated with an impaired HRQoL were identified. Results A total of 115 patients with aPL and/or systemic lupus erythematosus (SLE) were included (mean age 42.7 ± 14.1 years old, 86 women). In 53 patients APS was diagnosed. Compared to general population norms, patients with APS had an impaired HRQoL. SLE-associated APS patients had the worst HRQoL scores (physical component summary (PCS)=40.8 ± 10.6; mental component summary (MCS)=40.6 ± 16.5) in comparison with SLE or aPL patients without thromboembolic history. In APS patients, history of arterial thrombosis significantly impaired HRQoL (PCS score: 42.2 ± 9.4 vs 49.2 ± 8.5; MCS score: 33.9 ± 13.7 vs 44.6 ± 10.3). Conclusion Compared to the general population, APS patients experienced a lower HRQoL. In these patients, a history of arterial thrombosis significantly impaired HRQoL. Therefore, measurements of HRQoL should be included in APS patient management to assess the burden of the disease from a patient’s perspective and to provide patients with the support they need. [ABSTRACT FROM AUTHOR]

Budd Chiari syndrome (BCS) is defined as obstruction of hepatic venous outflow that can be located anywhere from small hepatic venules up to the entrance of inferior vena cava (IVC) into right atrium. Etiologies of BCS include myeloproliferative disorders, congenital, and acquired hypercoagulable states. Anticoagulation is the mainstay of treatment for all cases of BCS with a demonstrable hypercoagulable state. Interventional radiology procedures such as transjugular intrahepatic portosystemic shunting (TIPS) can be utilized to reduce portal hypertension and to improve complications related to portal hypertension. We present a patient with systemic lupus erythematosus who first presented with fever, weight loss, malar rash, alopecia, livedo reticularis, symmetric polyarthritis, pancytopenia, and class IV lupus nephritis when she was 23 years old. After receiving an induction treatment of cyclophosphamide and glucocorticoids, she received a maintenance treatment of azathioprine. She presented with ascites and abdominal pain when she was 36 and the abdominal imaging revealed reduced calibration of hepatic venules and intrahepatic segment of inferior vena cava. Lupus anticoagulant was positive and anti cardiolipin IgM and IgG were positive. Work up for hereditary hypercoagulable states was negative. Thus, the diagnosis was secondary antiphospholipid syndrome where BCS was the first clinical manifestation of the antiphospholipid syndrome. Patient was anticoagulated with warfarin and received diuretics for ascites. After the ascites became refractory to diuretics and the patient had multiple vertebral compression fractures due to volume overload secondary to ascites, she was successfully treated with TIPS. When control imaging was performed, 50% of stenosis was observed in the stent. Balloon dilation of the stent was performed. Interventional radiology techniques like TIPS can be used in BCS patients secondary to APS, in cases when medical treatment is insufficient to control complications of portal hypertension. In BCS patients secondary to APS, TIPS enables clinical improvement but due to the presence of endothelial dysfunction in APS patients, there is a risk of shunt dysfunction secondary to thrombosis or stenosis secondary to intimal hyperplasia. Therefore, strict anticoagulation and regular follow up of patients after TIPS is recommended. In cases with stent stenosis, reintervention may be necessary. [ABSTRACT FROM AUTHOR]

Background: Retinal vasculopathy including retinal artery occlusion (RAO) or retinal vein occlusion (RVO) was recently found to occur more frequently in antiphospholipid syndrome (APS) patients than non-APS patients. This study aims to investigate the clinical manifestation and risk factors of retinal vasculopathy among APS patients. Methods: In this single-center prospective cohort study, we evaluated APS patients with or without retinal vasculopathy during 2018–2020 at Peking Union Medical College Hospital. Clinical variables were compared, and a logistical regression model was built to explore risk factors. Hierarchical cluster analysis using Euclidean distances was applied to identify clusters of variables. Results: A total of 310 APS patients (67.4% female, mean age 38.1 years) were included, of whom 18 (5.8%) were diagnosed with retinal vasculopathy (9 with RVO and 9 with RAO). No significant differences were found among most demographic characteristics, clinical manifestations, or antibody profiles. APS-related heart valve disease (odds ratio OR 13.66, 95% confidence interval CI 4.55–40.98), APS nephropathy (OR 12.77, 95% CI 4.04–40.35), and thrombocytopenia (OR 2.63, 95% CI 1.01–6.89) were predictive of retinal vasculopathy. APS-related heart valve disease and nephropathy were also found to be statistically significant predictors in multivariate logistical regression analysis. Non-criteria manifestations were aggregated with retinal vasculopathy from a cluster analysis of variables. Conclusion: Patients with APS-related heart valve disease and nephropathy suffered a higher risk of retinal vasculopathy. The underlying mechanisms of aPL-associated retinal vasculopathy may involve thrombotic microangiopathy, leading to poor prognosis and therapeutic changes. [ABSTRACT FROM AUTHOR]

The antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by a hypercoagulability associated to vascular thrombosis and/or obstetric morbidity, is caused by the presence of antiphospholipid antibodies such as lupus anticoagulant, anti-β-2-glycoprotein 1, and/or anticardiolipin antibodies. In the obstetrical APS, antiphospholipid antibodies induce the production of proinflammatory cytokines and tissue factor by placental tissues and recruited neutrophils. Moreover, antiphospholipid antibodies activate the complement system which, in turn, induces a positive feedback leading to recruitment of neutrophils as well as activation of the placenta. Activation of these cells triggers myometrial contractions and cervical ripening provoking the induction of labor. In thrombotic and obstetrical APS, antiphospholipid antibodies activate endothelial cells, platelets, and neutrophils and they may alter the multimeric pattern and concentration of von Willebrand factor, increase the concentration of thrombospondin 1, reduce the inactivation of factor XI by antithrombin, increase the activation of factor XII, and reduce the activity of tissue plasminogen activator with the subsequent production of plasmin. All these effects result in less permeable clots, denser, thinner, and with more branched fibrin fibers which are more difficult to lysate. As a consequence, thrombosis, the defining clinical criterion of APS, complicates the clinical course of the patient. [ABSTRACT FROM AUTHOR]

Background: Not all patients fulfil criteria for specific autoimmune rheumatic diseases (ARDs) and are then defined as having non-criteria (nc)ARD. It is uncertain whether well-recognised associations with adverse pregnancy outcomes in patients with criteria ARD also exist in patients with ncARD or undifferentiated connective tissue disease (UCTD). Therefore, we undertook a systematic review of the prevalence of adverse pregnancy outcomes in various ncARD and UCTD compared with criteria ARD to identify whether there are increased risks and to examine for any benefits of treatment. Methods: This study was conducted in accordance with the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. A systematic literature review was performed using online databases including Medline and PubMed from inception to the beginning of April 2021 using appropriate keywords for various ARD and pregnancy outcomes. Results: After screening 665 articles, 36 articles were chosen for full text review and 15 selected for final analysis. There were eight studies of nc antiphospholipid syndrome (APS) of more than 7000 pregnancies and seven studies of UCTD of more than 1000 pregnancies. No studies of any other ncARD in pregnancy were identified. We found that patients with either ncAPS or UCTD seem to have an increased burden of poor pregnancy outcomes compared with the general population. Despite the heterogeneity and poor quality of the studies, we also noted that ncAPS and criteria APS patients may have similar rates of obstetric complications with standard and/or non-standard APS treatment regimens. Conclusion: Our findings of increased risks of poor pregnancy outcomes in patients with ncAPS or UCTD will be helpful for pre-pregnancy counselling and management of these patients in pregnancy and support their referral to specialist obstetric-rheumatology and obstetric-haematology clinics. [ABSTRACT FROM AUTHOR]

Highlights findings of research on renal disease in primary antiphospholipid syndrome (APS). Association of thrombotic microangiopathy with antiphospholipid antibodies; Hypertension and renal failure with primary APS and APS associated with systemic lupus erythematosus.

The aim of this paper is to analyze the epidemiologic, clinical, and immunologic characteristics of the antiphospholipid syndrome (APS), primary or secondary, in autoimmune patients from Northern Greece. Sixty-seven patients with APS were included (9 men, 13.4%, and 58 women, 86.6%). Fifty-two (77.6%) patients had secondary APS and 15 had primary APS (22.4%). The mean age was 46.0 ± 15.4 years and the mean follow-up period was 62.7 ± 15.0 months. Medical records were retrospectively analyzed from January 1994 until December 2001, according to a preestablished protocol. Eight patients (11.9%) had arterial thrombosis, 12 (17.9%) had vein thrombosis, 12 (17.9%) had thrombocytopenia, 20 (29.8%) had neurologic disorders, and 51.6% of the women in reproductive age had, at least 2 fetal losses (higher frequency in primary APS). Thirty-six patients (53.7%) had increased levels of both immunoglobulin G (Ige) and IgM anticardiolipin antibodies (ACA), 19 (28.4%) had IgG ACA only, and 12 (17.7%) had IgM ACA only. Antinuclear antibodies (ANA) were detected in 46 (68.6%) patients, and antineutrophil cytoplasmic antibodies (ANCA) in 29 (43.3%). All patients were prophylactically treated with aspirin (50–100 mg/day) and low-molecular-weight heparin and/or intravenous immunoglobulins-IVIGs occasionally (pregnant women). The findings of this study are, generally, similar to those described by others. Miscarriages seem to be more frequent in women with primary APS (p<0.05), compared to other studies. Differences between these findings and those described by others concerning epidemiologic, clinical, or immunologic data are discussed. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) and Primary Antiphospholipid Syndrome (PAPS) overlap clinical and immunological features. Therefore, misclassification of PAPS patients as SLE is a concern. The ACR/EULAR 2019 SLE classification has never been studied in PAPS. Objective: To verify if the ACR/EULAR 2019 SLE classification can correctly classify a PAPS patient as not having SLE and compare its performance with the SLICC 2012 SLE classification. Methods: One-hundred thrombotic PAPS patients who fulfilled the Sidney criteria were consecutively screened and those who attended the inclusion criteria were submitted to ACR/EULAR 2019 and SLICC 2012 classifications. Results: Sixty-seven PAPS patients were included in this study. The majority was female (89.6%) with median age at study inclusion of 45 years (35–53) and median PAPS disease duration of 13 years (8–19). PAPS correct classification was observed more often with ACR/EULAR 2019 than SLICC 2021 criteria (94.0% vs. 64.2%; p < 0.001). The 4 misclassified patients in ACR/EULAR 2019 were also misclassified in SLICC 2012. The comparison of misclassified patients to those correctly not classified as SLE resulted, for both criteria, in higher frequencies of hematological domain [ACR/EULAR 2019 (100% vs. 28.6%, p = 0.010) and SLICC 2012 (95.8% vs. 11.6%, p < 0.001)]. Further analysis of hematological manifestations revealed that for the ACR/EULAR 2019 leukopenia (100% vs. 22.2%, p = 0.004) and for the SLICC 2012 leukopenia/lymphopenia (91.7% vs. 7%, p < 0.001) were more frequent in misclassified group. Proteinuria (20.8% vs. 0%, p = 0.004) and low complement (45.8% vs. 20.9%, p = 0.033) were also more often observed in the incorrectly SLICC 2012 classified patients. Conclusion: ACR/EULAR 2019 had high accuracy for distinguishing PAPS from SLE, whereas the SLICC 2012 incorrectly classified more than one third of the PAPS patients as having SLE. [ABSTRACT FROM AUTHOR]

CAPS is an uncommon disease, characterized by clinical evidence of multiple organ involvement and histopathological evidence of multiple vessel occlusions, in patients with either primary or secondary antiphospholipid syndrome. The present series describes the clinical manifestations and autopsy findings of 12 patients with CAPS. Neurological involvement was considered the main cause of death in all of them. CNS pathology revealed thrombotic microangiopathy as well as small and large vessel occlusions in several brain areas. Neurological involvement in CAPS is strongly associated with thrombotic microangiopathy and should be considered a potential cause of death in these patients. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) and myeloproliferative neoplasms (MPN) are associated with an increased risk of thrombosis. The optimal management of patients with coexistent APS and MPN has not been defined. A single centre and systematic literature review of patients with coexistent APS and MPN was performed. Cases were divided into two groups based on whether they met international consensus criteria for APS. Of the 12 studies identified, eight were excluded (leaving five of a total 54 patients), as although antiphospholipid antibodies (aPL) were documented, the diagnosis of APS was not conclusively demonstrated. Another ten patients with definite APS were identified at our centre. Fifteen patients (ten females, five males) were therefore included in this analysis (eleven definite APS and four highly likely), median age 44 (range: 13–71) years. Nine had polycythaemia vera and six, essential thrombocythaemia. Thirteen of the 15 patients (86.7%) had thrombotic APS (seven with initial venous events and six arterial) and two (13.3%) had obstetric APS. Nine patients were single-positive, and six double-positive for aPL. None were triple aPL-positive. Four patients at our centre had recurrent thrombotic/obstetric events, including while on anticoagulation/antiplatelet treatment. [ABSTRACT FROM AUTHOR]

Objective: It has been reported that patients with antiphospholipid antibodies (aPL) and refractory migraine may experience symptomatic improvement with antithrombotic therapy, but this phenomenon has not been well studied. This study was undertaken to detail the response to trials of antithrombotic therapy in these patients. Methods: This is a retrospective study of 75 patients with refractory migraine and aPL who were given a 2-4 week trial of aspirin, clopidogrel and/or anticoagulation. Major response was defined as 50-100% improvement in frequency and/or severity of migraine; minor response: 25-49% improvement; no response: <25% improvement. Results: 66 patients were given a trial of aspirin: 47% responded (21% major); 60 patients were given a trial of clopidogrel: 83% responded (67% major); and 34 patients were given a trial of anticoagulation (usually apixaban): 94% responded (85% major). The response rate to any anti-thrombotic therapy was 89% (83% major). Many patients also noted improvement in non-headache symptoms. No patient experienced stroke. There was no major bleeding during any 2-4 week treatment trial and only 3 of 69 patients maintained on an antithrombotic regimen for a median follow up of 29.9 months (5-100) experienced major bleeding. Conclusions: There was a high rate of symptomatic response to antithrombotic therapy in this context and long-term follow up suggested an individualized symptom-derived antithrombotic regimen may be associated with a low bleeding risk. Our data support consideration of a 2-4 week trial of antithrombotic therapy, usually starting with antiplatelet therapy, in aPL-positive patients with refractory migraine, particularly if other treatment options have been exhausted. As a retrospective study, our data provide only Class IV level of evidence, but they suggest randomized controlled trials are warranted to validate these encouraging findings. [ABSTRACT FROM AUTHOR]

No difference in outcome between therapeutic and preventive anticoagulation in patients with superficial vein thrombosis involving the saphenous-femoral junction Keywords: anticoagulation; saphenous-femoral junction; superficial vein thrombosis (SVT); venous thromboembolism (VTE) EN anticoagulation saphenous-femoral junction superficial vein thrombosis (SVT) venous thromboembolism (VTE) 290 292 3 06/14/22 20220601 NES 220601 Following the demonstration that thrombosis involving the superficial veins of the lower extremities (SVT) is a less benign disease than previously thought,[1] several controlled studies have consistently shown that fondaparinux in preventive doses, low-molecular-weight heparins (LMWHs) in intermediate doses, and rivaroxaban in preventive doses are effective and safe strategies for preventing extension or recurrence of the disease, as well as progression to the deep vein system and migration to the pulmonary circulation.[2][3][4][5] [6] In all these clinical trials, patients with the thrombus head within 3 cm from the saphenous-femoral junction were not eligible for recruitment, as they were perceived as being at a higher risk of venous thromboembolic complications in the absence of an active drug, nor were they in studies addressing the treatment of deep vein thrombosis (DVT) because of the lack of involvement of the deep vein system. Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial. [Extracted from the article]

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune pathology that can involve any organ. Lupus-related acute pancreatitis (AP) is, together with lupus mesenteric vasculitis, an important cause of SLE-induced acute abdominal pain. Methods: A literature search was conducted using the terms "Pancreatitis" and "Lupus Erythematosus, Systemic" on PubMed/Medline and Web of Science from January 2007 to January 2020. Clinical characteristics, diagnostic approach, and treatment principles in SLE-related AP are presented in this review. Results: Mainly retrospective reports were identified. The reported incidence of SLE-associated AP ranges from 0.9 to more than 5% of patients. A total of 264 SLE patients were found in the selected research, with a net female predominance (sex ratio 9:1) and mean age of 31.4 years. Abdominal pain was virtually present in all cases. AP occurrence was more frequent in SLE patients with short disease duration, high activity scores, and multiorgan involvement. The AP definition was based on currently available guidelines and after exclusion of any other known causes (including iatrogenic, i.e. drugs), a diagnosis of "idiopathic" SLE-related AP might be sustained. Management is difficult, as there is no standardized therapeutic approach. Of note, glucocorticoid use remains still controversial as, especially for high doses, subsequent pancreatic injury may occur. Monitoring serum lipase levels after high dose steroids might be considered. One study reported beneficial prognostic effect of plasma exchange. Moreover, AP in SLE might raise awareness about macrophage activation syndrome association. Mortality up to one third of AP cases in SLE was reported. Conclusion: The SLE-related AP is a rare, but severe, life-threatening complication. Corticosteroids must be used with caution. Plasma exchange could be considered in selected cases. [ABSTRACT FROM AUTHOR]

Objectives: To compare and rank currently available pharmacological interventions for the prevention of recurrent miscarriage (RM) in women with antiphospholipid syndrome (APS). Methods: A search was performed using PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, CNKI, ClinicalTrials.gov, and the UK National Research Register on December 15, 2019. Studies comparing any types of active interventions with placebo/inactive control or another active intervention for the prevention of RM in patients with APS were considered for inclusion. The primary outcomes were efficacy (measured by live birth rate) and acceptability (measured by all-cause discontinuation); secondary outcomes were birthweight, preterm birth, preeclampsia, and intrauterine growth retardation. The protocol of this study was registered with Open Science Framework (DOI: 10.17605/OSF.IO/B9T4E). Results: In total, 54 randomized controlled trials (RCTs) comprising 4,957 participants were included. Low-molecular-weight heparin (LMWH) alone, aspirin plus LMWH or unfractionated heparin (UFH), aspirin plus LMWH plus intravenous immunoglobulin (IVIG), aspirin plus LMWH plus IVIG plus prednisone were found to be effective pharmacological interventions for increasing live birth rate (ORs ranging between 2.88 to 11.24). In terms of acceptability, no significant difference was found between treatments. In terms of adverse perinatal outcomes, aspirin alone was associated with a higher risk of preterm birth than aspirin plus LMWH (OR 3.92, 95% CI 1.16 to 16.44) and with lower birthweight than LMWH (SMD −808.76, 95% CI −1596.54 to −5.07). Conclusions: Our findings support the use of low-dose aspirin plus heparin as the first-line treatment for prevention of RM in women with APS, and support the efficacy of hydroxychloroquine, IVIG, and prednisone when added to current treatment regimens. More large-scale, high-quality RCTs are needed to confirm these findings, and new pharmacological options should be further evaluated. [ABSTRACT FROM AUTHOR]

Introduction: Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thromboembolic events, including ischemic stroke or complications in pregnancy, and the presence of antiphospholipid antibodies. Cervical artery dissection (CAD) is not an uncommon cause of stroke in young adults. The concomitant presence of APS and CAD is extremely rare. Methods: Two cases with APS who developed acute ischemic strokes related to CAD are reported. A comprehensive systematic literature search using the PubMed database was also conducted. Results: In Case 1, a 36-year-old woman who had been diagnosed with systemic lupus erythematosus and had been repeatedly positive for lupus anticoagulant tests developed an ischemic stroke caused by a vertebral artery dissection (VAD). After admission, she had a recurrent ischemic stroke, followed by considerable changes in steno-occlusive lesions of the vertebrobasilar artery system. In Case 2, a 36-year-old man developed multiple brain infarcts due to bilateral VAD with aneurysmal formations and associated with pulmonary embolism. The anticardiolipin antibody titer was repeatedly elevated after stroke. The literature review identified 8 patients with CAD associated with APS, involving the internal carotid artery in 6 patients and the middle cerebral artery and vertebral artery in 1 patient each. The patients were predominantly young and female, infrequently had atherosclerotic vascular risk factors, and were positive for various antiphospholipid antibodies. Conclusions: The current report described two rare cases of ischemic stroke caused by CAD secondary to APS, along with a review of the literature; the patients displayed characteristic clinical manifestations, implying specific mechanisms for cerebral artery disorders secondary to APS. [ABSTRACT FROM AUTHOR]

The current COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to distinct diagnostic and management challenges for front-line healthcare workers. The risk of excessive coagulation activation leading to a cascade of thrombotic events in critically ill patients with SARS-CoV-2 is now well reported. We discuss a recent case of COVID-19 with concurrent acute pulmonary embolism and a positive cardiolipin antibody (IgM). The presence of antiphospholipid antibodies is key to diagnosing antiphospholipid syndrome (APS). However, their presence can be transient or persistent after viral infections. Serial inflammatory markers in conjunction with anti-phospholipid antibody testing is critical for the diagnosis of APS in this emerging patient population. Our case report reviews details suggestive of APS in the setting of SARS-CoV-2 and aims to provide clinical diagnostic clues that could help warrant further workup and assist with management strategies. [ABSTRACT FROM AUTHOR]

Obstetric antiphospholipid syndrome (APS) remains a clinical challenge for practitioners, with several controversial points that have not been answered so far. This Obstetric APS Task Force met on the 16th International Congress on Antiphospholipid Antibodies in Manchester, England, to discuss about treatment, diagnostic and clinical aspects of the disease. This report will address evidence-based medicine related to obstetric APS, including limitations on our current management, the relationship between antibodies against domain 1 of β2GPI and obstetric morbidity, hydroxychloroquine use in patients with obstetric APS and factors associated with thrombosis after obstetric APS. Finally, future directions for better understanding this complex condition are also reported by the Task Force coordinators. [ABSTRACT FROM AUTHOR]