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Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and obstetric morbidity, with accurate laboratory examination of antiphospholipid antibodies (aPLs) being crucial for diagnosis. This study focused on anti-ß2 glycoprotein I (aß2GPI) antibodies and aimed to establish the first population-based cutoff values for aß2GPI IgA/IgM/IgG antibodies in non-pregnant women of reproductive age in Southwest China. The study cohort comprised 181 healthy women of reproductive age for study. Blood samples were collected on an early morning fast. Anti-ß2GPI antibodies including IgA, IgM and IgG were measured in serum using the HOB® BioCLIA kit. According to the Clinical and Laboratory Standards Institute (CLSI) guidelines, the study used non-parametric percentile methods to calculate the 95th, 97.5th, and 99th percentiles cutoff values for aß2GPI IgA/IgM/IgG antibodies, along with corresponding 90% confidence intervals (CI), while excluding outliers. A total of 168 independent samples were collected for verification, including 85 samples from healthy subjects and 83 samples from APS patients, in order to evaluate the analytical performance of the obtained cutoff values. The 99th percentile cutoff values were 3.36 RU/mL for aß2GPI IgA, 27.54 RU/mL for aß2GPI IgM and 1.81 RU/mL for aß2GPI IgG, which indicated that the levels of aß2GPI IgM antibodies were generally higher compared to those of IgA and IgG antibodies. Our established reference range was confirmed to be successful in validating the detected values of aß2GPI antibodies in all healthy controls. With the 99th percentile cutoff value, the sensitivity was 14.46% for aß2GPI IgA, 22.89% for aß2GPI IgG, and 9.64% for aß2GPI IgM in APS patients. This study established population-based cutoff values that are applicable to the local population for the accurate laboratory examination of aß2GPI antibodies in non-pregnant women of reproductive age. The study also recommends paying more attention to IgM positivity in women of reproductive age.

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INTRODUCTION: The objective of this study was to investigate both antiphospholipid antibodies (aPLs) and non-criteria aPLs (NC-aPLs) in relation with pregnancy outcomes. METHODS: We retrospectively analyzed 1574 pregnant women with experienced at least one miscarriage who were tested for aPLs and NC-aPLs, and compared their clinical characteristics, immune biomarkers, and pregnancy outcomes. The χ2 test or Fisher's exact test compared pregnancy outcomes among patients negative for all aPLs, positive for NC­aPLs subtypes, and positive for criteria aPLs subtypes. RESULTS: Multivariate logistic regression analysis indicated that positive aPLs (OR = 2.216, 95 % CI 1.381-3.558), and positive NC-aPLs (OR = 1.619, 95 % CI 1.245-2.106) are linked to adverse outcomes. For fetal loss, positive aPLs (OR = 2.354, 95 % CI 1.448-3.829), NC-aPLs (OR = 1.443, 95 % CI 1.076-1.936) were significant. Premature delivery was associated with positive NC-aPLs (OR = 2.102, 95 % CI 1.452-3.043). In the NC-aPLs positive group, the rate of adverse outcomes was higher in the multiple-positive subgroup (77.8 %) compared to the double-positive (52.3 %) and single-positive (37.0 %) subgroups. The rates of fetal loss and premature delivery were also higher in the multiple-positive NC-aPLs subgroup compared to the single-positive subgroup (48.1 % vs. 22.6 % for fetal loss and 57.1 % vs. 16.5 % for premature delivery). DISCUSSION: Our findings suggest that both aPLs and NC-aPLs are associated with an increased incidence of adverse pregnancy outcomes, and patients presenting with multiple NC-aPLs positivity were found to have a higher incidence of adverse outcomes compared to their single-positive counterparts.

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Thrombotic manifestations, mainly venous thromboembolism (VTE) and stroke, are the most common and potentially life-threatening presentations of antiphospholipid syndrome (APS). The management of APS requires the assessment of the antiphospholipid antibodies (aPL) profile, of concurrent systemic lupus erythematosus or other systemic autoimmune diseases and the presence of risk factors for cardiovascular disease and bleeding. Anticoagulation with vitamin K antagonists (VKA) remains the cornerstone of therapy for thrombotic APS. As platelets play a central role in APS, low-dose aspirin is the first option for primary thromboprophylaxis in asymptomatic aPL carriers, and also plays a role as combination therapy with VKAs in arterial thrombosis. Treatment with direct oral anticoagulants (DOACs) could be considered in certain low-risk situations, although they are not recommended in patients with arterial thrombosis or triple positive aPL. Adjuvant therapies such as hydroxychloroquine and statins may be useful in complex settings such as thrombotic recurrences or high risk of bleeding. In this article, we review the evidence and the recommendations of the guidelines for the treatment of APS, and provide a critical and practical approach of its management from our clinical perspective.

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

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

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Antiphospholipid antibodies (aPL) are a family of autoantibodies targeting phospholipid-binding proteins and are associated with several clinical settings, and most notably define the antiphospholipid syndrome (APS). These antibodies can be identified using a variety of laboratory tests, which include both solid-phase immunological assays and functional clotting assays that detect lupus anticoagulants (LA). aPLs are linked to a range of adverse medical conditions, such as thrombosis and complications affecting the placenta and fetus, potentially leading to morbidity and mortality. The specific aPL identified, along with the pattern of reactivity, correlates with the severity of these conditions. Therefore, laboratory testing for aPL is crucial for evaluating the risk of complications and for fulfilling certain classification criteria for APS, which are also applied as diagnostic markers in medical practice. This review provides an overview of the available laboratory tests currently for measuring aPL and discusses their clinical implications.

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In the 40 years since the original detailed description of antiphospholipid syndrome (APS), the condition has come to be regarded as one of the most common autoimmune diseases. The impact of the description has been enormous - for example, the recognition that some individuals with connective tissue diseases require anticoagulation rather than corticosteroids or anti-inflammatory treatment has bought about fundamental change in medical practice. In obstetrics, APS is now regarded as the most important prothrombotic cause of recurrent pregnancy loss - with pregnancy success improving from below 20% to current live birth rate over 80%. In neurology, APS may be associated with up to 20% of strokes in people under 40 - a striking figure not least in terms of medical economics, let alone in potentially preventable suffering. In vascular medicine, APS links immunology with thrombosis and vascular disease and may well provide insights into immunological factors in the pathogenesis of atherosclerosis.

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OBJECTIVES: This review aims to identify biological markers associated with the risk of recurrence of thrombotic and/or obstetric events in patients with antiphospholipid syndrome (APS). METHODS: A comprehensive review of literature was conducted to evaluate established and potential novel biological markers associated with thrombosis in APS. To this end, a PubMed literature search was conducted for the last twenty years using the following keywords or their combinations: thrombotic risk, recurrence of thrombosis, risk stratification, severity, predictive value. RESULTS: Previous studies showed that multiple aPL positivity correlates with an increased risk of thrombosis in APS. Moreover, the analysis of N-glycosylation of antiphospholipid antibodies (aPL) revealed that low levels of IgG sialylation, fucosylation or galactosylation increases the pro-inflammatory activity of aPL, predisposing to thrombosis. In addition, quantification of neutrophil extracellular traps (NETs) and antibodies directed against NETs (anti-NETs) in serum demonstrates promising prognostic utility in assessing APS severity. Oxidative stress plays a role in the pathogenicity of APS and paraoxonase 1 (PON1) activity emerges as a promising biomarker of thrombotic risk in APS. Furthermore, identification of novel antigenic targets involved in the pathophysiology of APS, such as lysobisphosphatidic acid (LBPA), had led to the discovery of unconventional aPL, antibodies directed against the LBPA (aLBPA), whose clinical value could make it possible to identify APS patients at high risk of thrombotic recurrence. CONCLUSION: The immunological profile of aPL, N-glycosylation of aPL, quantification of NETs and anti-NETs, analysis of biomarkers of oxidative stress and the discovery of aLBPA offer potential prognostic tools for risk stratification in APS patients.

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

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Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arteriovenous thrombosis and pathological pregnancy, accompanied by persistent antiphospholipid antibodies, (aPL). The incidence of APS is increasing year by year, clinicians lack of understanding of this type of disease, easy to misdiagnose and miss the diagnosis. Therefore, it is extremely important to establish a suitable animal model to reduce the process of disease development as much as possible and improve clinicians' understanding and understanding. This review will summarize the animal models of APS from the aspects of modeling methods, modeling mechanism, evaluation indicators and advantages and disadvantages of methods, providing a reference for finding an animal model highly similar to human APS, helping researchers to further clarify the pathogenesis of APS and find potential therapeutic targets, so as to achieve early diagnosis, early intervention, and ultimately improve the prognosis of patients.

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AIM: To analyze associations between clinical and morphological features of kidney involvement in patients with systemic lupus erythematosus. MATERIALS AND METHODS: In the retrospective cohort study, we enrolled adult (≥18 years) patients with morphologically proven lupus nephritis (LN) stratified according to the ISN/RPS classification. Systemic lupus erythematosus was classified in accordance with ACR/EULAR classification criteria (2019). Antiphospholipid syndrome was diagnosed according to the 2006 classification criteria. Disease activity was assessed with SELENA-SLEDAI score. RESULTS: We enrolled 62 patients with LN, among them 84% were females. Median age of SLE onset was 23 (16,3; 30,8) years. In all cases kidney involvement was accompanied by extrarenal manifestations, among which joint (82%), skin (57%) and hematological involvement (68%) was the most common. LN class I was proven in one patient, class II - in three patients, class III - in 24, including III+V in seven, class IV - in 18, including IV+V in two, class V - in 13, class VI - in three patients. APS nephropathy was diagnosed in 4 (6.5%) of patients with LN. The most common clinical manifestation was proteinuria (85%), however its prevalence, level and the frequency of nephrotic syndrome showed no significant differences between the LN classes. LN III/IV±V was characterized by the highest levels of serum creatinine (and the lowest eGFR) at the time of biopsy. CONCLUSION: LN is characterized by the high heterogeneity of the clinical and morphological manifestations, which makes LN class prediction impossible without kidney biopsy.

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Lupus nephritis (LN) is one of the most common organ-specific manifestations of systemic lupus erythematosus (SLE). Various clinical signs of LN develop in at least 50% of patients with SLE. In addition to LN, the spectrum of renal lesions associated with SLE also includes vascular pathology. One of the variants of renal microvascular injury is thrombotic microangiopathy (TMA), the mechanisms of which are diverse. The review focuses on the main forms of TMA, including antiphospholipid syndrome and nephropathy associated with antiphospholipid syndrome, TMA caused by complement system regulation disorders and deficiency of ADAMTS13. In most cases, these forms of TMA are combined with LN. However, they may also exist as a single form of kidney damage. This article discusses the TMA pathogenesis, the impact on kidney prognosis, and treatment options.

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RATIONALE: Adrenal infarction (AI) is a rare type of adrenal damage, which is relatively common in systemic lupus erythematosus, antiphospholipid antibody syndrome (APS) and pregnancy. The diagnosis of AI is mainly by computed tomography (CT) and magnetic resonance imaging, but is easily confused with other adrenal disease. Hence, this report details a condition of AI with systemic lupus erythematosus, APS and made a differential diagnosis from imaging. PATIENT CONCERNS: We report a case of a 55-year-old woman with pain in her fossa axillaries and inguinal regions. Then CT scan disclosed bilateral adrenal diseases, and the patient was diagnosed with systemic lupus erythematosus, APS and AI after additional autoimmune examinations. DIAGNOSES: The patient was diagnosed as systemic lupus erythematosus with lupus nephritis, hematological damage and oromeningitis, APS, AI and secondary blood coagulation disorders. INTERVENTIONS: The patient was treated with methylprednisolone, hydroxychloroquine and low molecular heparin. OUTCOMES: The patient relieves and remains well 1 year after treatment. LESSONS SUBSECTIONS: AI can be divided hemorrhagic and non-hemorrhagic, with bilateral lesions more common. In our case, the AI was bilateral, partially involved and non-hemorrhagic, and the "cutoff sign" was first put forward in CT, which might assist the diagnosis.

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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.

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

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OBJECTIVE: Antiphospholipid syndrome (APS) is an autoimmune disease mainly affecting young individuals. Testing for antiphospholipid antibodies is recommended for young patients who are suspected to have APS. Yet, it is hard to differentiate APS from other acquired thrombophilia disorders in elderly-onset APS patients. This study aim to investigate the characteristics and prognosis of elderly-onset APS. METHODS: This is an observational cohort study. Thrombotic APS patients who underwent follow-ups between 2009 and 2022 were included. Elderly-onset APS patients (onset age ≥60 years) were compared to non-elderly-onset APS patients (onset age <60 years) and matched cases of elderly non-APS patients (age ≥60 years with thrombosis). RESULTS: A total of 161 APS patients were included in this study, 45 (28.0%) were elderly-onset APS. Stroke (35.6% vs. 18.1%, p = .018) was more common at disease onset in elderly-onset APS patients. Compared to non-elderly-onset patients, elderly-onset APS patients were associated with a higher number of cardiovascular risk factors. Elderly-onset APS patients showed significantly lower positive rate (51.1% vs. 71.6%, p = .014) and ratios [1.24 (1.01-1.38) vs. 1.37 (1.16-1.77), p = .004] of lupus anticoagulant. Elderly-onset APS patients had a significantly higher 10-years cumulative all-cause mortality (p < .001) and APS-related mortality than non-elderly-onset patients (p = .002) and elderly non-APS patients (p = .040). CONCLUSIONS: Elderly-onset APS patients have unique disease characteristics with higher 10-years cumulative all-cause mortality and APS-related mortality. Early recognition and control of comorbidities may reduce the recurrence of thrombosis and mortality in elderly-onset APS patients.

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Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe pre-eclampsia and severe placental insufficiency. The persistent presence of antiphospholipid antibodies (aPLs) is the most important laboratory characteristic of OAPS. OAPS severely affects the reproductive health of women of childbearing age in China. Reports indicate that approximately 9.6% stillbirths, 11.5% severe pre-eclampsia, and 54% recurrent miscarriages are associated with OAPS or aPLs. However, the pathogenesis of OAPS remains unclear. Previously, thrombosis at the maternal-fetal interface (MFI) was considered the main mechanism of OAPS-related pathological pregnancies. Consequently, the use of low molecular weight heparin and aspirin throughout pregnancy was recommended to improve outcomes in OAPS patient. In recent years, many studies have found that thrombosis in MFI is uncommon, but various inflammatory factors are significantly increased in the MFI of OAPS patients. Based on these findings, some clinicians have started using anti-inflammatory treatments for OAPS, which have preliminarily improved the pregnancy outcomes. Nevertheless, there is no consensus on these second-line treatments of OAPS. Another troubling issue is the clinical diagnosis of OAPS. Similar to other autoimmune diseases, there are only classification criteria for OAPS, and clinical diagnosis of OAPS depends on the clinicians' experience. The present classification criteria of OAPS were established for clinical and basic research purposes, not for patient clinical management. In clinical practice, many patients with both positive aPLs and pathological pregnancy histories do not meet the strict OAPS criteria. This has led to widespread issues of incorrect diagnosis and treatment. Timely and accurate diagnosis of OAPS is crucial for effective treatment. In this article, we reviewed the epidemiological research progress on OAPS and summarized its classification principles, including: 1) the persistent presence of aPLs in circulation; 2) manifestations of OAPS, excluding other possible causes. For the first point, accurate assessment of aPLs is crucial; for the latter, previous studies regarded only placenta-related pregnancy complications as characteristic manifestations of OAPS. However, recent studies have indicated that adverse pregnancy outcomes related to trophoblast damage, such as recurrent miscarriage and stillbirth, also need to be considered in OAPS. We also discussed several key issues in the diagnosis and treatment of OAPS. First, we addressed the definition of non-standard OAPS and offered our opinion on defining non-standard OAPS within the framework of the 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) APS criteria. Then, we discussed the advantages and disadvantages of different aPL testing methods, emphasizing that harmonizing results across platforms and establishing specific reference values are keys to resolving controversies in aPL testing results. We also introduced the application of non-criteria aPLs, especially anti-phosphatidylserine/prothrombin antibody (aPS/PT) and anti-ß2 glycoprotein Ⅰ domain Ⅰ antibody (aß2GPⅠDⅠ). Additionally, we discussed aPL-based OAPS risk classification strategies. Finally, we proposed potential treatment methods for refractory OAPS. The goal is to provide a reference for the clinical management of OAPS.

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Antiphospholipid Syndrome (APS), characterized by hypercoagulability and pregnancy morbidity, poses a significant clinical challenge when involving organ systems, such as the endocrine system. APS can directly and indirectly influence the anterior and posterior lobes of the pituitary gland. The thyroid gland exhibits involvement, especially in patients with positive anticardiolipin antibodies, yet the clinical significance of the relationship with APS remains elusive. The pancreas, often overlooked, manifests in diverse ways, from pancreatitis to implications in diabetes. Adrenal insufficiency emerges as a common endocrine manifestation of APS, with adrenal hemorrhage or infarction being a presenting manifestation. Adrenal gland involvement has also been reported in the context of catastrophic APS. Pregnancy complications and infertility might be effects of APS on the female ovaries, while testicular torsion and decreased sperm concentration and total sperm count have been reported as rare effects of APS on male testes.

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