The 2023 ACR/EULAR antiphospholipid syndrome classification criteria identify patients at high risk of complications.

OBJECTIVES: This study aims to evaluate the utility of the 2023 ACR/EULAR antiphospholipid syndrome (APS) classification criteria in identifying primary APS patients at high risk of complications. METHODS: In this single-center study, primary APS patients were classified according to both the revised Sapporo criteria and the 2023 ACR/EULAR criteria. The risk of complications was assessed using the adjusted Global Antiphospholipid Syndrome Score (aGAPSS). RESULTS: Forty-five patients (73% females, median age 49 years) were included. Thirty-six patients met the 2023 ACR/EULAR criteria, all of whom also fulfilled the revised Sapporo criteria. Additionally, four out of nine patients not meeting the 2023 ACR/EULAR criteria satisfied the revised Sapporo criteria. Agreement rate between the two classification criteria was 91%, with a Cohen's kappa index of 0.66. Patients meeting the 2023 ACR/EULAR criteria had significantly higher aGAPSS scores compared to those who did not (13, 8-13 vs. 3, 0-5; p = 0.005). Furthermore, 55% of patients meeting the 2023 ACR/EULAR criteria were categorized as high risk based on aGAPSS scores, while those not meeting the criteria were predominantly categorized as low risk (77%). Interestingly, patients not meeting the 2023 ACR/EULAR criteria but fulfilling the revised Sapporo criteria had significantly higher aGAPSS scores compared to those not meeting either set of criteria (7, 5-13 vs. 0, 0-1.5; p = 0.015). CONCLUSION: The 2023 ACR/EULAR criteria effectively identify primary APS patients at increased risk of complications, as indicated by the aGAPSS score. Key Points • Identifying primary APS patients at high risk of complications remains a significant challenge. • The 2023 ACR/EULAR criteria show a correlation with the aGAPSS score, exhibiting the highest correlation with laboratory domains and minimal correlation with clinical domains. • The 2023 ACR/EULAR classification criteria are effective in identifying primary APS patients at high risk of complications.

Identification of common MicroRNAs expression signatures in antiphospholipid syndrome and thromboembolic disease: A scoping review.

BACKGROUND: Antiphospholipid syndrome (APS) is an acquired autoimmune disorder characterized by distinct pathophysiological mechanisms leading to heterogeneous manifestations, including venous and arterial thrombosis. Despite the lack of specific markers of thrombosis risk in APS, some of the mechanisms responsible for thrombosis in APS may overlap with those of other thromboembolic diseases. Understanding these similarities is important for improving the assessment of thrombosis risk in APS. MicroRNAs (MiRNAs) are RNA molecules that regulate gene expression and may influence the autoimmune response and coagulation. PURPOSE: In this scoping review we aimed to investigate shared miRNAs profiles associated with APS and other thromboembolic diseases as a means of identifying markers indicative of a pro-thrombotic profile among patients with APS. DATA COLLECTION AND RESULTS: Through a comprehensive search of scientific databases, 45 relevant studies were identified out of 1020 references. miRs-124-3p, 125b-5p, 125a-5p, and 17-5p, were associated with APS and arterial thrombosis, while miRs-106a-5p, 146b-5p, 15a-5p, 222-3p, and 451a were associated with APS and venous thrombosis. Additionally, miR-126a-3p was associated with APS and both arterial and venous thrombosis. CONCLUSION: We observed that APS shares a common miRNAs signature with non-APS related thrombosis, suggesting that miRNA expression profiles may serve as markers of thrombotic risk in APS. Further validation of a pro-thrombotic miRNA signature in APS is warranted to improve risk assessment, diagnosis, and management of APS.

Effect of vitamin D3 on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19.

OBJECTIVE: To investigate the effect of a single oral dose of 200,000 IU of vitamin D3 on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19. METHODS: This is a post-hoc, exploratory analysis from a double-blind, placebo-controlled, randomized clinical trial performed in two centers in Sao Paulo, Brazil. Hospitalized patients with COVID-19 were randomly assigned to receive either vitamin D3 (n = 97) or placebo (n = 97). In this post-hoc analysis, the endpoints were titers and frequency of anti-ß2-Glycoprotein-I (aß2-GP) and Anticardiolipin (aCL) antibodies [Immunoglobulin G, M and A (IgG, IgM and IgA)]. RESULTS: Overall mean (SD) age was 55.3 (13.9) years, Body Mass Index (BMI) was 32.2 (7.1 kg/m2), and 106 participants (54.6 %) were male. There was a significant group by time interaction (p = 0.046) for frequency of aCL IgG, with increased values from baseline to discharge in the placebo group [n (%), from 13 (13.4) to 25 (25.8)] compared to the vitamin D3 [from 25 (25.8) to 29 (29.9)]. However, the frequency of aCL IgG did not change between the groups on discharge. No significant differences between vitamin D3 and placebo groups were found for any other autoantibodies. CONCLUSION: These findings do not support the use of a single oral dose of 200,000 IU of vitamin D3 to modulate autoantibodies in hospitalized patients with moderate to severe COVID-19.

Plasma cell-free DNA as a monitoring tool for high-risk pregnancies associated with antiphospholipid syndrome.

INTRODUCTION: Despite thromboprophylaxis, women with antiphospholipid syndrome (APS) face high-risk pregnancies due to proinflammatory and prothrombotic states. This highlights the need for new monitoring and prognostic tools. Recent insights into the pathophysiological role of neutrophil activation and extracellular trap (NET) formation in this syndrome led to the exploration of plasma cell-free DNA (cfDNA), a derivative of NETosis, as a promising biomarker. MATERIALS AND METHODS: cfDNA was isolated and quantified from plasma samples of healthy pregnant women (control group, HC) and women with APS (APS group). We assessed the physiological variability of cfDNA across the three trimesters in HC. Levels of cfDNA were compared between APS and HC by gestational trimester. ROC curve analysis was performed to evaluate the efficacy of cfDNA levels for classifying APS patients. Furthermore, cfDNA levels in pregnant women with APS with obstetric complications were compared to those from uncomplicated pregnancies. RESULTS: Among HC, cfDNA significantly increased in the third trimester compared to the first and second. Elevated cfDNA levels in APS compared to HC were observed in the first and second trimesters. First-trimester cfDNA levels demonstrated the highest classification ability to discriminate between APS and HC patients (AUC: 0.906). Among APS, those with complicated pregnancies (fetal growth restriction, preeclampsia, placenta accreta) exhibited significantly elevated cfDNA levels in the second trimester. CONCLUSIONS: Elevated levels of cfDNA in pregnant women with APS, particularly among those with obstetric complications, supports further investigation into the potential of cfDNA as a valuable tool in the obstetric management of women with APS.

Updates in diagnosis and treatment of pediatric antiphospholipid syndrome.

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.

Etiology and diagnostic approach of recurrent miscarriage at a reference center in Bucaramanga, Colombia.

OBJECTIVE: The purpose of this study was to determine the etiologies of recurrent miscarriage in our hospital and whether its diagnostic approach followed the recommendations of the American Society of Reproductive Medicine (ASRM) guidelines published in 2012 and the National Institute for Health and Care Excellence (NICE) guidelines published in 2011. METHODS: This was a retrospective study. The medical records of 158 patients diagnosed with recurrent miscarriage between 2013 and 2018 at Santander University Hospital were reviewed. The Institutional Review Board of HUS approved the study in May 2020. RESULTS: The most common etiologies identified were protein S deficiency, thrombophilia, and cervical insufficiency, with incidence rates of 25.9%, 10.7%, and 3.8%, respectively. Moreover, the most frequently requested diagnostic tests were for protein S, protein C, and anti-phospholipid IgG. Abnormal results for protein S were obtained in 49% of the patients, whereas lupus anticoagulant was abnormal in 12.8%, and Factor V Leiden gene mutations in 8.5% of the patients. Three substantial deviations from the recommended diagnostic approach for recurrent miscarriage by international guidelines were identified in our population: the lack of request for cytogenetic analysis of pregnancy tissue, request for cytogenetic analysis for the parents in only 0.6% of the study sample, and the request for imaging tests to assess uterine anatomy in only 6.3% of the studied population. Both the ASRM and NICE guidelines were only partially followed with a combined adherence rate of 66.5%. CONCLUSION: The diagnostic approach for recurrent miscarriage poses important clinical challenges when compared to the recommendations of international guidelines. Therefore, the development of a local recurrent miscarriage assessment protocol is proposed in our institution.

Cerebrovascular disease in patients with antiphospholipid antibody syndrome: a transcranial Doppler and magnetic resonance imaging study.

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

Diferencias en la conclusión final de la búsqueda de anticoagulante lúpico en pacientes anticoagulados con antagonistas de la vitamina K / Differences in the final conclusion of the search for lupus anticoagulant in patients anticoagulated with vitamin K antagonists

Resumen Introducción. La detección de anticoagulante lúpico (AL) en pacientes que reciben el tratamiento con antagonistas de la vitamina K (AVK) es todavía una asignatura pendiente. Algunas guías recomiendan realizar todas las pruebas en la mezcla equimolar del plasma del paciente y el pool de plasmas normales (PN+PP), en aquellos pacientes con RIN<3. Sin embargo, la última guía de la ISTH sugiere no determinar AL en pacientes con AVK. Objetivo. Comparar la conclusión final de los estudios de AL, realizando las pruebas de tamizaje y confirmatorias en el plasma puro (PP) y en la mezcla (PP+PN), en pacientes en tratamiento con AVK. Población. 90 pacientes con diagnóstico previo de AL persistente, que al momento de su inclusión estaban en tratamiento con AVK con RIN < 3. Todos habían sido estudiados por segunda vez para confirmar el diagnóstico de AL persistente, a los tres meses, bajo tratamiento anticoagulante con heparina de bajo peso molecular y luego continuaron con el tratamiento con AVK. Materiales y métodos. Se realizaron los ensayos de tamizaje y confirmatorio del tiempo de veneno de víbora de Russell (dRVVT y cRVVT) y del tiempo de coagulación de sílice (sSCT y cSCT). Se preparó el pool de plasmas normales con 40 donantes de sangre, que fueron negativos para la evaluación de AL. Los puntos de corte fueron establecidos localmente de acuerdo a la guía ISTH. Resultados. 33/90 pacientes fueron AL positivo tanto en PP como en PP+PN, 27 negativos y 30 discordantes. 46 de las 90 muestras fueron positivas por dRVVT en PP, pero sólo 18/90 fueron positivas por ensayo de dRVVT en PP+PN. El valor de kappa para la medida de la concordancia entre el ensayo dRVVT en ambas situaciones fue de 0,21 (IC del 95 % = 0,047-0,374). 52/90 fueron negativos por ensayo SCT en PP y 50/90 fueron negativos en PP+PN. 31/90 fueron positivos en ambos casos. Sólo 9/90 fueron positivos por SCT en PP+PN y negativos en PP. El índice kappa para el SCT fue 0,64 (0,431-0,844). Discusión. Aunque realizar las pruebas de AL en PP+PN en pacientes anticoagulados con AVK es una práctica habitual, de acuerdo con estos resultados no es una buena opción, porque podría dar un diagnóstico falsamente negativo o positivo, dependiendo del ensayo. La discrepancia entre usar o no la mezcla es mayor en el ensayo de Drvvt.

Abstract Introduction. The detection of lupus anticoagulant (LA) in patients who are on vitamin K antagonist (VKA) treatment is still an unresolved issue. Some guidelines recommend performing all tests on the equimolar mixture of the patient's plasma plus normal plasma pool (PN+PP) in those patients with INR<3. However, the latest ISTH guideline suggests not determining LA in patients with VKA. AIM. To compare the final conclusion of LA studies, performing screening and confirmatory tests in pure plasma (PP) and in the mixture (PP+PN), in patients receiving VKA treatment. Population. 90 patients with a previous diagnosis of persistent AL, who at the time of inclusion were in treatment with VKA with INR < 3. All had been studied for a second time to confirm the diagnosis of persistent LA, three months later, under anticoagulant treatment with low molecular weight heparin and then continued treatment with VKA. Materials and methods. Screening and confirmatory tests of Russell's viper venom time (dRVVT and cRVVT) and silica coagulation time (sSCT and cSCT) were performed. The normal plasma pool was prepared with 40 blood donors, who were negative for the AL evaluation. The cut-off points were established locally according to the ISTH guideline. Results. 33/90 patients were LA positive considering PP and PP+PN, 27 were negative and 30 discordant. 46 of the 90 samples were positive by dRVVT in PP but only 18/90 were positive by dRVVT assay in PP+PN. The kappa value for the measure of agreement between the dRVVT test in both situations was 0.21 (95% CI = 0.047-0.374). 52/90 were negative by SCT assay in PP and 50/90 were positive in PP+PN. Only 9/90 were positive by SCT in PP+PN and negative in PP. The kappa index for the SCT was 0.638 (0.431-0.844). Discussion. Although performing LA tests on the PP+PN mixture in anticoagulated patients with VKA is a common practice, according to these results, it is not a good option because they could give a false negative or positive diagnosis, depending on the assay. The discrepancy between using or not using the mixture is greater in dRVVT´s assay.

Síndrome antifosfolipídico trombótico en una mujer con enfermedad mixta del tejido conectivo. Reporte de caso / Thrombotic antiphospholipid syndrome in a woman with mixed connective tissue disease. Case report

Introducción: El síndrome de anticuerpos antifosfolípidos es una enfermedad au-toinmune sistémica poco frecuente, produce hipercoagulabilidad con riesgo de trombosis. Para el diagnóstico se utilizan los criterios ACR/EULAR APS del 2023. El tratamiento es anticoagulantes y antiagregantes plaquetarios. La enfermedad mixta del tejido conectivo es enfermedad autoinmunitaria sistémica con la asociación de manifestaciones clínicas de otras entidades autoinmunes. Objetivo:Describir la presentación de dos enfermedades sistémicas autoinmunes poco frecuentes en conjunto, con el propósito de contribuir con un enfoque prác-tico para el diagnóstico y manejo. Presentación del caso: Se describe una paciente de 37 años que presentó un episodio de tromboembolia pulmonar secundario a síndrome de anticuerpos anti-fosfolípidos y en los 6 meses previos tuvo síntomas compatibles con enfermedad mixta del tejido conectivo. Discusión: La presencia de dos entidades autoinmunes, síndrome de anticuerpos antifosfolípidos y enfermedad mixta del tejido conectivo presentadas en conjunto y cuyo debut de complicaciones fue una tromboembolia pulmonar, encontrándo-se presencia de múltiples autoanticuerpos positivos entre estas anticuerpos an-tifosfolipídicos y anti-U1 snRNP, es un reto diagnóstico al diferenciar entre otras enfermedades del tejido conectivo como lupus eritematoso sistémico, esclerosis sistémica cutánea, enfermedad mixta del tejido conectivo y artritis reumatoide. El tratamiento se basó en las características del paciente y su condición clínica al momento del diagnóstico. Conclusiones: El síndrome de anticuerpos antifosfolipídicos conlleva la presencia de un episodio trombótico, por otro lado, su asociación con una enfermedad mixta del tejido conectivo es poco frecuente y puede aumentar su morbimortalidad.

Introduction: Antiphospholipid antibody syndrome is a rare systemic autoimmu-ne disease that produces Antiphospholipid antibody syndrome is a rare systemic autoimmune disease that causes hypercoagulability with risk of thrombosis. For diagnosis, the ACR/EULAR APS 2023 criteria are used. Treatment is anticoagulants and antiplatelet agents.Mixed connective tissue disease is a systemic autoimmune disease with the asso-ciation of clinical manifestations of other autoimmune entities.Objective:To describe the presentation of two rare autoimmune systemic diseases toge-ther, with the purpose of contributing a practical approach to diagnosis and management.Case presentation: 37-year-old patient with an episode of pulmonary thromboem-bolism secondary to antiphospholipid antibody syndrome and in the previous 6 months he had symptoms compatible with mixed connective tissue disease.Discussion:The presence of two autoimmune entities, antiphospholipid antibody syndrome and mixed connective tissue disease presented together and whose de-but of complications was a pulmonary thromboembolism, finding the presence of multiple positive autoantibodies between these antiphospholipid antibodies and an-ti-U1 snRNP, is a diagnostic challenge in differentiating between other connective tissue diseases such as systemic lupus erythematosus, cutaneous systemic sclero-sis, mixed connective tissue disease and rheumatoid arthritis. Treatment was based on the patient's characteristics and clinical condition at the time of diagnosis.Conclusions: Antiphospholipid antibody syndrome entails the presence of a thrombotic episode; on the other hand, its association with a mixed connective tissue disease is rare and may increase its morbidity and mortality.

Results and prognosis of kidney transplantation in lupus nephritis: Experience of an Argentine center.

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.

Loss of opportunities in the diagnosis and treatment of primary obstetric antiphospholipid syndrome (POAPS): from theory to reality.

OBJECTIVES: (I) To identify and measure the clinical consequences of a delayed diagnosis in patients with primary obstetric antiphospholipid syndrome (POAPS), in terms of time and events associated to antiphospholipid syndrome (APS), and (II) to evaluate the impact of their treatment status on perinatal outcomes, before and after diagnosis. METHODS: This retrospective multicentre study included 99 POAPS women who were separated in two groups of timelines based on their diagnostic status: group 1: women who met the clinical criteria for POAPS; group 2: included the same patients from group 1 since they meet the laboratory criteria for APS. In group 1, we assessed the following variables: obstetric events, thrombotic events and time (years) to diagnosis of APS. We also compared perinatal outcomes between patients in group 1 vs. group 2. Women in group 2 were treated with standard of care for POAPS. Simple and multivariable logistic regression analyses were performed. RESULTS: Regarding the impact of the delay on diagnosis, a total of 87 APS-related events were recorded: 46 miscarriages, 32 foetal losses and 9 premature deliveries before the 34th week due to preeclampsia, and one thrombosis. The estimated rate of preventable events was 20.58 per year/100 patients. The mean diagnostic delay time was 4.27 years. When we compared both groups during pregnancy, we found that patients in group 1 (no treatment) had a higher association with pregnancy losses [OR = 6.71 (95% CI: 3.59-12.55), p < 0.0001]. CONCLUSION: Our findings emphasize the negative impact of POAPS underdiagnosis on patient health and the critical importance of a timely intervention to improve pregnancy outcomes. Key Points •Our study shows the relevance of underdiagnosis on primary obstetric antiphospholipid syndrome (POAPS). •These patients presented a high risk of APS-related events with each passing year. •Shorter diagnostic delay time was observed in the reference centres.

Sub-segmental pulmonary thromboembolism in a pregnant woman with generalized lupus erythematosus, triple-negative antiphospholipid syndrome, and protein C deficiency. A case report.

Autoimmune diseases and thrombophilic disorders, notably antiphospholipid syndrome (APS) and protein S deficiency, present a formidable challenge in pregnancy, substantially increasing the risk of thromboembolic complications by up to 20%. Pulmonary thromboembolism (PTE), characterized by a significantly higher maternal mortality rate, is of particular concern. APS, defined by the presence of antiphospholipid antibodies, emerges as a pivotal risk factor for PTE during pregnancy, especially in women exhibiting triple negativity. Concurrently, protein S deficiency further amplifies vulnerability to thromboembolic events, establishing a high-risk scenario for pregnant individuals. In a case involving a 29-year-old pregnant woman with a history of generalized lupus erythematosus, triple-negative antiphospholipid syndrome, and protein S deficiency, sudden-onset dyspnea prompted thorough investigation. Despite her complex medical history, a multidisciplinary approach led to the accurate diagnosis and successful management of subsegmental pulmonary thromboembolism, ensuring the well-being of both mother and fetus. Effectively managing PTE during pregnancy demands a comprehensive, multidisciplinary approach involving collaboration among obstetricians, internists, rheumatologists, and hematologists. Accurate diagnosis, tailored anticoagulation strategies, and continuous monitoring stand as indispensable pillars for maternal and fetal well-being.

Damage measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in antiphospholipid antibody-positive patients included in the APS ACTION registry.

OBJECTIVES: Our primary objective was to quantify damage burden measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in aPL-positive patients with or without a history of thrombosis in an international cohort (the APS ACTION cohort). Secondly, we aimed to identify clinical and laboratory characteristics associated with damage in aPL-positive patients. METHODS: In this cross-sectional study, we analysed the baseline damage in aPL-positive patients with or without APS classification. We excluded patients with other autoimmune diseases. We analysed the demographic, clinical and laboratory characteristics based on two subgroups: (i) thrombotic APS patients with high vs low damage; and (ii) non-thrombotic aPL-positive patients with vs without damage. RESULTS: Of the 826 aPL-positive patients included in the registry as of April 2020, 586 with no other systemic autoimmune diseases were included in the analysis (412 thrombotic and 174 non-thrombotic). In the thrombotic group, hyperlipidaemia (odds ratio [OR] 1.82; 95% CI 1.05, 3.15; adjusted P = 0.032), obesity (OR 2.14; 95% CI 1.23, 3.71; adjusted P = 0.007), aß2GPI high titres (OR 2.33; 95% CI 1.36, 4.02; adjusted P = 0.002) and corticosteroid use (ever) (OR 3.73; 95% CI 1.80, 7.75; adjusted P < 0.001) were independently associated with high damage at baseline. In the non-thrombotic group, hypertension (OR 4.55; 95% CI 1.82, 11.35; adjusted P = 0.001) and hyperlipidaemia (OR 4.32; 95% CI 1.37, 13.65; adjusted P = 0.013) were independent predictors of damage at baseline; conversely, single aPL positivity was inversely correlated with damage (OR 0.24; 95% CI 0.075, 0.77; adjusted P = 0.016). CONCLUSIONS: DIAPS indicates substantial damage in aPL-positive patients in the APS ACTION cohort. Selected traditional cardiovascular risk factors, steroids use and specific aPL profiles may help to identify patients more prone to present with a higher damage burden.

Effect of vitamin D3 on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19

Abstract Objective: To investigate the effect of a single oral dose of 200,000 IU of vitamin D3 on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19. Methods: This is a post-hoc, exploratory analysis from a double-blind, placebo-controlled, randomized clinical trial performed in two centers in São Paulo, Brazil. Hospitalized patients with COVID-19 were randomly assigned to receive either vitamin D3 (n = 97) or placebo (n = 97). In this post-hoc analysis, the endpoints were titers and frequency of anti-β2-Glycoprotein-I (aβ2-GP) and Anticardiolipin (aCL) antibodies [Immunoglobulin G, M and A (IgG, IgM and IgA)]. Results: Overall mean (SD) age was 55.3 (13.9) years, Body Mass Index (BMI) was 32.2 (7.1 kg/m²), and 106 participants (54.6 %) were male. There was a significant group by time interaction (p = 0.046) for frequency of aCL IgG, with increased values from baseline to discharge in the placebo group [n (%), from 13 (13.4) to 25 (25.8)] compared to the vitamin D3 [from 25 (25.8) to 29 (29.9)]. However, the frequency of aCL IgG did not change between the groups on discharge. No significant differences between vitamin D3 and placebo groups were found for any other autoantibodies. Conclusion: These findings do not support the use of a single oral dose of 200,000 IU of vitamin D3 to modulate autoantibodies in hospitalized patients with moderate to severe COVID-19.

Presentación atípica de síndrome antifosfolípido

El síndrome antifosfolípido es considerado un trastorno del colágeno asociado a presentaciones clínicas a edades intermedias con incidencias no mayores de 5 casos por cada 100.000 personas. Su espectro clínico oscila en la presencia de manifestaciones trombóticas multisistémicas de origen vascular. Sin embargo, las manifestaciones no vasculares tienen un espectro raro en su presentación habitual. Se presenta el caso de un varón de 64 años con manifestaciones oculares relacionadas a amaurosis fugaz asociado a alteraciones estructurales retinianas. Los hallazgos de tamizajes realizados fueron fuertemente sugestivos de trombofilias primarias. Se aplicó perfil para síndrome antifosfolípido el cual fue positivo, por lo que se instauró anticoagulación plena.

Antiphospholipid syndrome is considered a collagen disorder associated with clinical presentations at intermediate ages with incidences of no more than 5 cases per 100,000 people. Its clinical spectrum ranges from the presence of multisystem thrombotic manifestations of vascular origin. However, non-vascular manifestations have a rare spectrum in their usual presentation. The case of a 64-year-old man with ocular manifestations related to amaurosis fugax associated with retinal structural alterations is presented. The findings of screening performed were strongly suggestive of primary thrombophilia. A profile for antiphospholipid syndrome was applied, which was positive and therefore, full anticoagulation was initiated.

Experiencing pregnancy in the context of lupus and antiphospholipid syndrome: a grounded theory / Experimentando el embarazo en el contexto del lupus y del síndrome antifosfolípido: una teoría fundamentada / Vivenciando a gestação no contexto do lúpus e da síndrome antifosfolípide: uma teoria fundamentada

ABSTRACT Objective: To understand the meanings attributed to pregnancy in the context of Lupus and antiphospholipid syndrome by women and healthcare professionals. Method: Qualitative research, using Symbolic Interactionism as a theoretical framework and Grounded Theory, a constructivist perspective. Data were collected between January and August 2022, through online interviews with 27 women with Lupus located on the social network Facebook and in-person or remote interviews with 12 healthcare professionals. Results: The theoretical model constructed has two categories: "Equal conditions, distinct experiences: experiencing the gestational process" shows that obstetric complications and lack of connection with healthcare professionals trigger negative meanings to the experience; and "Therapeutic management interfering in the attribution of meanings to the experience", demonstrates that the way women interact with healthcare professionals and how they manage treatment favors a positive reframing. Final considerations: The meanings attributed to pregnancy are elaborated and modified according to the interpretation of previous and current experiences, healthcare trajectory and interactions with healthcare professionals. Previous guidance, planning, bonding and trust in healthcare professionals enable positive meanings, while obstetric complications, unqualified assistance and lack of bonding with professionals provide negative meanings.

RESUMEN Objetivo: Comprender los significados atribuidos al embarazo en el contexto del Lupus y del síndrome antifosfolípido por mujeres y profesionales de la salud. Método: Investigación cualitativa, que utilizó como marco teórico el Interaccionismo simbólico y metodológico, la Teoría Fundamentada, una vertiente constructivista. Los datos fueron recolectados entre enero y agosto de 2022, a través de entrevistas online a 27 mujeres con Lupus ubicadas en la red social Facebook y entrevistas presenciales o remotas a 12 profesionales de la salud. Resultados: El modelo teórico construido tiene dos categorías: "Condiciones iguales, experiencias diferentes: vivir el proceso gestacional" muestra que las complicaciones obstétricas y la falta de conexión con los profesionales de la salud desencadenan significados negativos a la experiencia; y Gestión terapéutica interfiriendo en la atribución de significados", demuestra que la forma en que las mujeres interactúan con los profesionales de la salud y cómo conducen el tratamiento favorece la resignificación positiva.. Consideraciones finales: Los significados atribuidos al embarazo son elaborados y modificados según la interpretación de experiencias pasadas y actuales, trayectoria de atención e interacciones con profesionales de la salud. La orientación previa, la planificación, la vinculación y la confianza en los profesionales de la salud posibilitan significados positivos, mientras que las complicaciones obstétricas, la asistencia no calificada y la falta de vínculo con los profesionales proporcionan significados negativos.

RESUMO Objetivo: Compreender os significados atribuídos à gravidez, no contexto do Lúpus e da Síndrome Antifosfolípide, por mulheres e profissionais de saúde. Método: Pesquisa qualitativa, que utilizou como referencial teórico o Interacionismo simbólico e metodológico, a Teoria Fundamentada nos Dados, vertente construtivista. Os dados foram coletados entre janeiro e agosto de 2022, mediante entrevistas on-line com 27 mulheres com Lúpus, localizadas na rede social Facebook e em entrevistas presenciais ou remotas com 12 profissionais de saúde. Resultados: O modelo teórico construído possui duas categorias: "Condições iguais, experiências distintas: vivenciando o processo gestacional" mostra que complicações obstétricas e ausência de vínculo com os profissionais de saúde desencadeiam significados negativos à experiência; e "O manejo terapêutico interferindo na atribuição dos significados à experiência" demonstra que a forma com que a mulher interage com os profissionais de saúde e conduz o tratamento favorece a ressignificação positiva. Considerações finais: Os significados atribuídos à gestação são elaborados e modificados conforme a interpretação de experiências anteriores e atuais, trajetória assistencial e interações com os profissionais de saúde. A orientação prévia, o planejamento, o vínculo e a confiança nos profissionais de saúde possibilitam significados positivos. Já, as complicações obstétricas, a assistência não qualificada e ausência de vínculo com os profissionais produzem significados negativos.

Retinal vein and artery occlusion as the first manifestation of primary antiphospholipid syndrome in a pediatric patient / Oclusão arterial e venosa como primeira manifestação da síndrome antifosfolipide primária em criança

ABSTRACT Antiphospholipid syndrome is an acquired autoimmune disease characterized by hypercoagulability associated with recurrent venous and arterial thromboembolism in the presence of antiphospholipid antibodies. Herein, we report a case of rapid sequential retinal vein and artery occlusion as the first manifestation of a primary antiphospholipid syndrome triggered by an acute Mycoplasma infection in a previously healthy 11-year-old patient. On day 1, ophthalmoscopy revealed a central retinal vein occlusion. The patient developed temporal branch retinal artery occlusion the next day. On day 3, a central retinal artery occlusion was observed. Serum lupus anticoagulant, immunoglobulin (Ig) G anticardiolipin, IgG anti-β2-glycoprotein 1 antibody, and Mycoplasma pneumoniae IgM antibody levels were increased. Thus, retinal vascular occlusions can be the first manifestation of primary antiphospholipid syndrome. Although it may not improve visual prognosis, prompt diagnosis and treatment are essential to avoid further significant morbidity.

RESUMO A síndrome antifosfolipide é uma doença autoimune adquirida caracterizada por hipercoagulabilidade associada a tromboembolismo venoso e arterial recorrente na presença de anticorpos antifosfolipídicos. Aqui, relatamos um caso clínico de oclusão sequencial de veia e artéria da retina como primeira manifestação de uma síndrome antifosfolipíde primária desen­cadeada por uma infeção aguda por Mycoplasma num paciente de 11 anos previamente saudável. No primeiro dia, a oftalmoscopia revelou uma oclusão da veia central da retina. No dia seguinte, o paciente desenvolveu uma oclusão do ramo temporal da artéria central da retina. No terceiro dia, uma oclusão da artéria central da retina foi diagnosticada. Os níveis de anticoagulante lúpico sérico, anticorpos IgG anticardiolipina e IgG anti-β2-glicoproteína 1 e anticorpos IgM para Mycoplasma pneumoniae estavam aumentados. As oclusões vasculares retinianas podem ser a primeira manifestação da síndrome antifosfolipíde primária. Apesar do prognóstico visual ser reservado, o seu diagnóstico e o tratamento imediatos são essenciais para evitar outras morbilidades associadas.

Evaluation of core decompression outcome in systemic lupus erythematosus with hip osteonecrosis: a retrospective cohort study

Abstract Background Osteonecrosis is a major cause of morbidity for patients with systemic lupus erythematosus (SLE). Although core decompression is an approved and trusted technique to prevent further joint deterioration, this surgical method seems to be less beneficial for SLE patients. We aimed to evaluate the outcomes of core decompression in SLE patients with primary stages of femoral head osteonecrosis. Methods In this study, 23 patients (39 affected hip joints) with osteonecrosis of the femoral head with stage II of the disease, based on the Ficat-Arlet classification system, underwent core decompression. Also, patients demographic characteristics, clinical data, medication history, comorbidities, immunological findings, hip plain radiographs, history of total hip arthroplasty after core decompression, and patients satisfaction with joint function according to the Oxford hip score questionnaire were obtained. Results In the study, 53.8% of affected joints showed signs of radiographic deterioration in follow-up imaging. Sixty-one and a half percent (61.5%) of patients had unsatisfactory joint performance. A third (33.3%) of affected hip joints underwent total hip arthroplasty up to 5 years from core decompression. SLE patients with a history of receiving bisphosphonate were 83.2% less dissatisfied with their joint function than patients without a history of bisphospho-nate use (P < 0.02). Of the 23 studied cases, the mean cumulative dose of prednisolone before and after core decompression surgery was 46.41 mg and 14.74 mg respectively. Besides, one case (2.6%) that had a high anti-phospholipid antibodies level during follow-up did not have any radiographic deterioration, and 9 cases (23.1%) had some degrees of radiographic deterioration. Conclusions The patients group that used bis-phosphonate, had a higher level of satisfaction with joint function after core decompression. Patients with high-level anti-phospholipid antibodies are related to a poor prognosis after core decompression.

Factores de predicción relevantes en la supervivencia de pacientes con síndrome antifosfolípido / Relevants predictions factors in the survival of patients with antiphospholipid syndrome

Introducción: Los pacientes con síndrome antifosfolípido desarrollan morbilidad y mortalidad significativas a pesar del tratamiento actual. Es imperativo, identificar factores pronósticos y medidas terapéuticas para prevenir estas complicaciones. Objetivo: Determinar los factores relevantes en la predicción de la supervivencia en los pacientes con síndrome antifosfolípido. Métodos: Se realizó un estudio longitudinal analítico de una cohorte histórica de personas con síndrome antifosfolípido, diagnosticados, según los criterios de Sapporo/Sydney y colaboradores en la consulta de enfermedades autoinmunes sistémicas del Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro», Villa Clara, del año 2000 al 2015. Se estudiaron variables demográficas y clínicas. En cada caso se determinó el tiempo de supervivencia con relación al evento muerte. Se aplicó el método de Kaplan Meier para calcular la supervivencia global y determinar las variables predictoras de la mortalidad. Según el estudio de los estadígrafos de comparación interestratos(Log-Rank) se demostró la significación estadística con la prueba de Chi cuadrado de homogeneidad. Resultados: De los 128 pacientes estudiados, 118 fueron femeninos y 10 masculinos (111 de piel blanca y 17 no blancos). La supervivencia global fue de 67,1 % con una media de 13,37 años. Las variables más relevantes que aportaron a la mortalidad en relación con menor supervivencia fueron: leucopenia, linfopenia, color de la piel no blanca, y el no uso de aspirina, con medias de supervivencia de 8,83; 8,17; 10,72; 12,10 años, respectivamente. Conclusiones: La identificación temprana de los factores pronósticos de supervivencia permite implementar estrategias oportunas e individualizadas en pacientes con síndrome antifosfolípido.

Introduction: patients with antiphospholipid syndrome develop significant morbidity and mortality despite current treatment. Identifying prognostic factors and therapeutic measures to prevent these complications is indispensable. Objective: to determine relevant factors in the prediction of survival in patients with antiphospholipid syndrome. Methods: a longitudinal analytical study was carried out on cohorts with antiphospholipid syndrome who were diagnosed according to the Sapporo-Sydney criteria and collaborators in the systemic autoimmune disease consultation at "Arnaldo Milián Castro" Clinical and Surgical University Hospital in Villa Clara from 2000 to 2015. Demographic and clinical variables were studied. The survival time in relation to the death event was determined in each case. The Kaplan - Meier method was applied to calculate overall survival and determine the predictor variables for mortality. According to the study of inter-strata comparison statistics (Log-Rank), statistical significance was demonstrated with the Chi-square test of homogeneity. Results: a number of 118 patients were female and 10 male from the 128 studied (111 white-skinned and 17 non-white). Overall survival was 67.1% with a mean of 13.37 years. The most relevant variables that contributed to mortality in relation to lower survival were leukopenia, lymphopenia, non-white skin color and non-use of aspirin, with mean survival of 8.83; 8.17; 10.72; 12.10 years, respectively. Conclusions: the early identification of survival prognostic factors allows us the implementation of timely and individualized strategies in patients with antiphospholipid syndrome.

Primary antiphospholipid syndrome with and without limb ischemia: A retrospective observational study.

OBJECTIVE: To compare clinical and laboratory data obtained from patients with primary Antiphospholipid Syndrome (PAPS) with and without limb ischemia (LI). METHODS: A transverse study with 66 (83.3% female) PAPS patients was performed. All data were evaluated. Patients were subdivided into one of two groups: PAPS with LI and PAPS without LI and compared. RESULTS: Sixty-six primary APS were selected. PAPS with LI group exhibited a longer disease duration (p = .012) and more arterial events (p = .002). A lower frequency of venous events was observed in PAPS with LI (p = .007), and deep venous thrombosis (p = .016). Furthermore, PAPS with LI patients had more deficiency of protein C of coagulation (p = .015) than the others. CONCLUSION: PAPS and LI have a distinct clinical and laboratory spectra from those without LI and it is characterized by an increased frequency of protein C deficiency, and a lower frequency of venous events, deep venous thrombosis and IgM anticardiolipin.