Epidemiology of thromboembolic events in children and adolescents with antiphospholipid syndrome: A systematic review with meta-analysis.

BACKGROUND AND AIM: This was a systematic review and meta-analysis of the prevalence of thromboembolic events in children and adolescents with antiphospholipid syndrome (APS). METHODS: We searched PubMed, EMBASE and Web of Science to select relevant articles published between 1 January 2000 and 27 February 2022. We used the random-effects meta-analysis to estimate pooled point prevalence rates of thromboembolic events in studies with a minimum sample size of 30. RESULTS: We included five studies reporting data of 336 children and adolescents with primary APS and secondary APS (SAPS). Pooled point prevalence rates of initial general thrombosis, arterial thrombosis, venous thrombosis and stroke in individuals with seropositive APS were 98.2% (95% confidence interval [CI] 87.5-100), 27.6% (95% CI 21.4-34.2), 51.1% (95% CI 38.2-63.9) and 13.4% 95% CI (6.3-22.7), respectively. Pooled point prevalence rates of initial arterial and venous thromboses in children and adolescents with SAPS were 45.7% (95% CI 21.1-71.6) and 29.2% (95% CI 14.8-46), respectively. CONCLUSION: Arterio-venous thromboembolism is highly frequent in children and adolescents with SAPS. More studies using thrombotic and non-thrombotic APS classification criteria are warranted to better assess the frequency and predictors of thromboembolism in age- and ancestry-diverse pediatric populations affected by different types of APS.

Risk factors for damage accrual in primary antiphospholipid syndrome: A retrospective single-center cohort study.

BACKGROUND: Despite anticoagulant therapy, a antiphospholipid syndrome (APS) has a higher rate of recurrent events, which can lead to damage accrual and a negative impact on life quality. OBJECTIVES: To evaluate the risk factors and APS subsets associated with damage accrual. PATIENTS/METHODS: We conducted a retrospective single-center study. We reviewed the medical records of 282 APS patients, with a median age of 36 (IQR 30-46) years and a median of 195 (IQR 137-272) months. The primary endpoint was damage accrual during follow-up, defined as organ/tissue impairment present for at least six months or causing permanent loss. The secondary endpoints were early organ damage within six months of disease onset and death. RESULTS: Eighty (28.4%) patients presented damage accrual; 52.5% developed damage within six months of APS onset, and 41.3% had more than one organ involved. Neuropsychiatric involvement, affecting 38.8% of the patients, was the most frequent, followed by peripheral vasculopathy and renal involvement, 35% either. Death happened in 7 (2.5 %) patients; damage accrual was associated with a 6-fold risk of death [OR 6.7 (95% CI 1.3-35.1), p = 0.03]. Microangiopathy and non-criteria manifestations were independent risk factors for damage accrual with 5-fold and 4-fold higher risk, respectively [(OR 4.9 (95% CI 2.1-11.7), p < 0.0001 and (OR 3.8 (95% CI 1.5-10.1), p = 0.007]. The cumulative incidence of damage accrual increased by 5.7-fold and 3.6-fold in patients with microangiopathy and non-criteria manifestations. CONCLUSIONS: APS patients had a higher frequency of damage accrual. Microangiopathy and non-criteria manifestations were independent risk factors for damage accrual.

The meaning of non-criteria clinical manifestations in a real-life primary antiphospholipid syndrome cohort.

OBJECTIVES: We aimed to evaluate the prevalence of non-criteria clinical features in patients with primary antiphospholipid syndrome (APS), and to assess their relationship to thrombosis and damage. METHODS: We retrospectively included 177 primary APS patients, and/or patients who only achieved the serological Sydney criteria but had thrombocytopenia and/or haemolytic anaemia. We registered demographics, serology, treatment, thrombotic/obstetric manifestations and non-criteria clinical manifestations (cutaneous, haematologic, renal, heart valve disease, and neurological). We scored the DIAPS and a modified SLICC index. We used logistic regression and reported OR with 95% CI. RESULTS: 78% were women with a median follow-up of 6.7 years. Thrombosis was found in 74% of patients, 29.3% had obstetric features, and 64% had non-criteria clinical manifestations. The frequency of the non-criteria clinical manifestation was: haematologic 40.1%, cutaneous 20.9%, neurologic 18%, cardiac 5% and renal 4.5%. Non-criteria features were associated with LA (OR 2.3, 95% 1.03-5.1) and prednisone use (OR 8.2, 95% CI 1.7-39.3). A DIAPS score ≥1 was associated with thrombosis (OR 53.1, 95% CI 17.8-15.2), prednisone use (OR 0.27, CI 95% 0.09-0.83) and neurological involvement (OR 6.4, 95% CI 1.05-39.8); whereas a modified SLICC ≥ 1 with thrombosis (OR 10.2; IC 95% 4.43-26.1), neurological involvement (OR 6.4, 95%CI 1.05-39.8), obstetric features (OR 0.32 CI 95% 0.12-0,81) and cutaneous features (OR 5.3, CI 95% 1.4-19), especially livedo reticularis (OR 5.45; IC 95% 1.49-19.8). CONCLUSIONS: Non-criteria clinical manifestations are common and associated with LA. Among them, neurologic involvement and the presence of livedo were associated with damage accrual.

The prevalence and incidence of thrombotic primary antiphospholipid syndrome in adults aged 18-49 years: A population-based study in a mountain community in northern Italy.

OBJECTIVE: To estimate prevalence and incidence of thrombotic Primary Antiphospholipid Syndrome (PAPS) in the general population aged 18-49 years. METHODS: The study was carried out in Valtrompia, a valley in northern Italy, in 2011-2015. The identification of PAPS cases leveraged three integrated sources: 1) Rheumatology Unit at the University Hospital; 2) General Practitioners; 3) hospital discharge codes of patients admitted for thrombotic events. RESULTS: Prevalence and incidence were estimated as 22.9 (95% C.I. 11.4-41.0) and 5.0 (2.6-8.7) cases per 100,000 individuals, respectively. The estimates were 28.3 and 4.8, and 17.2 and 5.1 in males and females, respectively. The type of disease onset was mainly of arterial type in men and venous in women. CONCLUSIONS: Thrombotic PAPS was found to be a rare disease in this population-based study. Prevalence and incidence were not significantly different between males and females aged 18-49 years, but a different type of onset was observed.

Pediatric Presentation of Antiphospholipid Syndrome: A Review of Recent Literature With Estimation of Local Prevalence.

We aimed to investigate the epidemiology, the clinical and laboratory characteristics of the pediatric involvement of antiphospholipid syndrome (APS), by performing a review of the current evidence and reviewing local experience in the Northwest Italy. To achieve this, we performed a detailed literature search to identify articles describing clinical and laboratory characteristics of pediatric APS. In concomitance, we conducted a registry-based study collecting data from the Piedmont and Aosta Valley Rare Disease Registry including pediatric patients diagnosed with APS in the last 11 years. The literature review led to inclusion of six articles with a total of 386 pediatric patients (65% females, 50% with systemic lupus erythematosus (SLE) as concomitant diagnosis). Rates of venous and arterial thrombosis were 57 and 35%, respectively. "Extra-criteria manifestations" included mostly hematologic and neurologic involvement. Almost one-quarter of patients (19%) reported recurrent events and 13% manifested as catastrophic APS. A total of 17 pediatric patients (mean age 15.1 ± 2.8, 76% female) developed APS in the Northwest of Italy. In 29% of cases, SLE was a concomitant diagnosis. Deep vein thrombosis was the most frequent manifestation (28%) followed by catastrophic APS (6%). The estimated prevalence of pediatric APS in Piedmont and Aosta Valley Region is 2.5/100,000 people, whereas the estimated annual incidence is 0.2/100,000 inhabitants. In conclusion, clinical manifestations of pediatric APS seem to be more severe and with a high prevalence of noncriteria manifestations. International efforts are needed to better characterize this condition and to develop new specific diagnostic criteria to avoid missed/delayed diagnosis in children with APS.

Trends in and outcomes of delivery hospitalizations with lupus and antiphospholipid syndrome.

OBJECTIVE: To assess trends and outcomes associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) during US delivery hospitalizations. STUDY DESIGN: The National Inpatient Sample from 2000 to 2019 was used for this repeated cross-sectional analysis. We identified delivery hospitalizations with and without SLE. Temporal trends in SLE during delivery hospitalizations were determined using joinpoint regression. Adjusted logistic regression models accounting for demographic, clinical, and hospital factors were used to determine adjusted odds ratios (aORs) for adverse outcomes based on the presence or absence of SLE. RESULTS: Of an estimated 76 698 775 delivery hospitalizations identified in the NIS, 79386 (0.10%) had an associated diagnosis of SLE. Over the study period, SLE increased from 6.7 to 14.6 cases per 10 000 delivery hospitalizations (average annual percent change 4.5%, 95% CI 4.0-5.1). Deliveries with SLE had greater odds of non-transfusion severe morbidity (aOR 2.21, 95% CI 2.00, 2.44) and underwent a larger absolute increase in morbidity risk over the study period. SLE was associated with a range of other adverse outcomes including preterm delivery, eclampsia, cesarean delivery, and blood transfusion. CONCLUSION: The proportion of deliveries to women with SLE has increased over time in the US, and SLE and APS are associated with a broad range of adverse outcomes.

Unveiling the Link Between Antiphospholipid Antibodies and Cognitive Dysfunction in the Almenara Lupus Cohort.

OBJECTIVE: Cognitive dysfunction is a prevalent manifestation of systemic lupus erythematosus (SLE). There is evidence for the role of antiphospholipid (aPL) antibodies on its etiopathogenesis. Our objective was to identify the association between aPL antibodies and cognitive dysfunction in SLE patients. METHODS: This cross-sectional study included 135 patients evaluated from March 2015 to October 2017 at one center. Cognitive deficit was measured using the NEUROPSI test. Disease activity and damage were ascertained using the SLEDAI-2K (SLE Disease Activity Index 2000) and the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), respectively; aPL antibodies were measured by enzyme-linked immunosorbent assay. The association between cognitive dysfunction and aPL antibodies was evaluated using univariable and multivariable linear regression models adjusted for age, sex, education, socioeconomic status, disease duration, SLEDAI-2K, SDI, mean current dose of prednisone, time of exposure to glucocorticoids, and drug use (immunosuppressants, hydroxychloroquine, aspirin, and warfarin). RESULTS: One hundred thirty-one patients (97.1%) were women; their mean (SD) age was 46.6 (12.5) years; 59 patients (43.7%) had positivity for at least 1 aPL antibody. IgM anticardiolipin (aCL) was positive in 24.5%, IgG in 13.5%, IgM aß2GP1 in 16.8%, IgG anti-ß2 glycoprotein in 24.6%, and the lupus anticoagulant in 5.3%. Ninety patients (66.7%) had some cognitive dysfunction. In the univariable analysis, a significant correlation between the NEUROPSI score and IgM aCL antibodies was found (B = -20.87 [SE, 3.2]; p < 0.001), which remained significant in the multivariable model (B = -13.89 [SE, 3.14]; p < 0.001). CONCLUSIONS: IgM aCL antibodies are associated with cognitive dysfunction in patients with SLE. Larger and longitudinal studies are needed to assess the impact of these findings.

The estimated prevalence of antiphospholipid antibodies and criteria-antiphospholipid syndrome in subjects with renal thrombotic microangiopathy.

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 ß2-glycoprotein-I (anti-ß2GPI) 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-ß2GPI, (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.

PREVALENCE OF ANTIPHOSPHOLIPID SYNDROME AMONG PREGNANT WOMEN IN LAUTECH TEACHING HOSPITAL OGBOMOSO NIGERIA.

Background: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by clinical thrombotic events which may be arterial or venous vasculature associated with the presence of antiphospholipid antibodies (aPL) in patient plasma. Majority of the studies done in this part of the world utilized single auto-antibody to phospholipids or phospholipid binding protein which resulted in an underestimation of the actual prevalence of this treatable disease entity. Hence, this study incorporates the use of triple auto-antibodies to determine the prevalence of APS among pregnant women in LAUTECH Teaching Hospital, Ogbomoso. Aim: To determine the prevalence of antiphospholipid syndrome using triple autoantibodies among pregnant women attending LAUTECH Teaching Hospital, Ogbomoso. Methodology: The study was a longitudinal descriptive design that involved eighty pregnant women with pregnancy complications and apparently eighty healthy pregnant women as control. Participants were tested for APS (antibeta-2-glycoprotein one (Antiß2GP1), anticardiolipin antibody (ACA), and lupus anticoagulant (LAC)) at first contact and persistent positivity after twelve-week intervals using the ELISA method. Results: The prevalence of persistent positivity to anti-phospholipids antibodies in this study are 28.8% and 2.5% among the study and control groups respectively. Persistent positivity to ACA was evident in 26.3%, ß2-GP1 in 21.1% and LAC in 16.3% of participants in the study group and ACA (2.5%), ß2-GP1 (1.3%) and LAC (2.5%) in the control group respectively. Persistent positivity to anti-phospholipids syndrome was associated with hypertension and recurrent miscarriage (≥3). Conclusion: Findings in this study revealed that the prevalence of APS among pregnant women with pregnancy complications using triple auto-antibodies was 28.8%, while the prevalence among healthy pregnant women was 2.5%. This indicates an underestimation of the actual prevalence of APS among pregnant women using single or double autoantibody. Hence, triple auto-antibodies screening is advised as a routine screening during pregnancy especially among those with a previous history of pregnancy complications.

[Mental disorders in patients with systemic lupus erythematosus: association with activity and the course of rheumatic disease].

AIM: To clarify the relationship between the clinical and psychopathological features of mental disorders, clinical and laboratory manifestations of activity and the nature of the course of systemic lupus erythematosus (SLE). MATERIALS AND METHODS: The study included 119 patients - 98 (82.4%) women, mean age 36.5±12.4 years (M±SD) - with a reliable diagnosis of SLE (EULAR/ACR 2019 criteria), 51 (29.5%) of them - with secondary antiphospholipid syndrome - APS (International criteria of 2006). RESULTS: Among patients with SLE a high frequency of anxiety-depressive spectrum disorders (ADSD) and cognitive impairment (CI) was revealed. There was an association of greater severity of depression with high SLE activity index, acute/subacute onset of the disease course according to the classification of V.A. Nasonova, relapsing-remitting and chronic active current disease activity patterns of SLE according to the classification of S. Barr - M. Petri. Anxiety disorders were associated with subacute onset and relapsing-remitting disease activity patterns of SLE and were not associated with SLE activity index. Bipolar disorder was detected more often in patients with chronic SLE. Acute psychosis/delirium was associated with acute onset of SLE. Organic CI was associated with APS, chronic onset and long quiescent disease activity patterns of SLE. The episindrome and schizotypal disorder in patients with SLE are more often caused by concomitant APS. CONCLUSION: Patients with high SLE activity index should be of particular concern to rheumatologists regarding the diagnosis of depressive disorders. Patients with concomitant APS need timely diagnosis and treatment of CI and episindrome in order to improve the prognosis of the disease and the overall quality of life.

Forecasting the Future of Antiphospholipid Syndrome: Prospects and Challenges.

Antiphospholipid syndrome (APS) is an autoimmune condition affecting young patients, primarily women, negatively impacting their quality of life. APS is under-recognized and underdiagnosed and can have devastating results if untreated, mainly due to uncontrolled thrombosis. Research in the past decades has led to several breakthroughs with important implications for clinical practice. Here, we summarize the state of APS diagnosis, treatment, pathophysiology, and research directions that hold promise for advancing diagnosis and treatment.

Síndrome antifosfolípidos catastrófico en México. Revisión de la bibliografía / Catastrophic antiphospholipid syndrome in Mexico. Literature review

El síndrome antifosfolípidos catastrófico (SAFC) es una entidad rara. Se han reportado aproximadamente 600 casos en todo el mundo, y se desconoce la prevalencia en México. Objetivo: Conocer la prevalencia estimada de SAFC en México. Material y métodos: Se realizó una búsqueda bibliográfica de casos clínicos aislados o series de casos en los diversos buscadores, utilizando los términos «síndrome antifosfolípidos catastrófico» y «México», en mayo de 2022. Resultados: Encontramos una serie de casos retrospectivos en necropsias que incluyeron 12 casos, dos reportes que incluyeron 2 casos cada uno, y también se encontraron reportes de 11 casos clínicos aislados; estas publicaciones se generaron entre 2003 y 2020. En total, se tienen datos de 27 casos de SAFC, de los cuales 16 corresponden al síndrome antifosfolípidos primario, 10 en asociación con lupus eritematoso sistémico y 1 caso de esclerosis sistémica. La tasa de prevalencia estimada en la población mexicana en 2022 es de 2 casos por cada 10.000.000 de habitantes. La mortalidad estimada fue del 68% en esta serie de casos. Conclusión: Los casos de SAFC en México están subreportados; sin embargo, identificarlos ayudará a mejorar las estrategias diagnósticas y terapéuticas que se utilizan actualmente en el país, incentivando la implementación de la triple terapia y, en casos refractarios, el uso de eculizumab, para reducir la mortalidad actual. (AU)

Catastrophic antiphospholipid syndrome (CAPS) is a rare entity, approximately 600 cases have been reported around the world, and the prevalence in Mexico is unknown. Objective: To determine the estimated prevalence of CAPS in Mexico. Material and methods: A literature search of isolated clinical cases or case series was conducted in diverse search engines, using the terms: «catastrophic antiphospholipid syndrome» and «Mexico» in May 2022. Results: We found a series of retrospective cases in autopsies that included 12 cases, two reports that included 2 cases each, and reports of 11 isolated clinical cases; these publications were generated between 2003 and 2020. In total, we collected data on 27 cases of CAPS, of which 16 correspond to primary antiphospholipid syndrome, 10 are associated with systemic lupus erythematosus, and 1 case corresponds to systemic sclerosis. The estimated prevalence rate in the Mexican population in 2022 is 2 cases per 10,000,000 inhabitants. The estimated mortality was 68% in this case series. Conclusion: Cases of catastrophic antiphospholipid syndrome in Mexico are underreported; identifying them will help improve current diagnostic and therapeutic strategies used in the country, encouraging the implementation of triple therapy and, in refractory cases, the use of eculizumab, to reduce current mortality. (AU)

Comorbid association of obstructive sleep apnea (OSA) and thrombotic primary antiphospholipid syndrome (tPAPS): A more severe phenotype?

OBJECTIVE: We aimed to evaluate the frequency of obstructive sleep apnea (OSA) in patients with thrombotic primary antiphospholipid syndrome (tPAPS), to investigate the performance of screening tools for OSA in this scenario and to compare clinical/laboratorial differences in tPAPS patients with and without OSA. METHODS: We consecutively enrolled patients with tPAPS to undergo sleep studies using a portable monitor. OSA was defined as apnea-hypopnea index ≥15 events/h. Frequency of OSA in tPAPS was evaluated and compared with age-, gender-, and BMI-matched controls (1:3 ratio) from the Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Next, we tested the performance of three different screening tools for assessing OSA in patients with tPAPS. Finally, patients with tPAPS were stratified according to OSA status comparing their clinical and laboratory characteristics (including damage burden measured by Damage Index for Antiphospholipid Syndrome [DIAPS] and biomarkers associated with thrombosis) using standard statistical procedures. RESULTS: Fifty-two patients were included for analysis (females: 82.7%; mean age: 48 ± 14 years; body-mass index: 31.1 ± 6.5 Kg/m2; 25% with moderate-severe OSA). When compared to matched controls from ELSA-Brasil (n = 115), there was no significant differences in the frequencies of OSA (tPAPS: 12/42 [28.6%] vs. controls: 35/115 [30.4%], p = 0.821). Among screening tools, NoSAS had the highest area under ROC curve (AUC 0.806, CI 95% 0.672-0.939, p = 0.001), followed by STOP-Bang (AUC 0.772, CI 95% 0.607-0.938, p = 0.004). Patients with comorbid tPAPS and OSA presented higher levels of von Willebrand factor (vWF) (median 38.9 vs. 32.6, p = 0.038) and DIAPS (median 5 vs. 2, p = 0.020), when compared to those without OSA. OSA remained statistically associated with higher DIAPS, even after controlling for age, disease duration and BMI. CONCLUSION: OSA is common in patients with tPAPS, with rates comparable to a non-referred population. Both NoSAS and STOP-Bang scores seems to be useful for screening OSA in these patients. Patients with tPAPS+OSA had higher damage burden and higher levels of vWF, which might suggest a more severe phenotype of tPAPS in this scenario.

Anti-thrombotics and major adverse cardiovascular events in anti-phospholipid syndrome: a cross-sectional study using the 2016-2018 National Inpatient Sample database.

OBJECTIVE: This study assessed the relationship between anti-thrombotics and major adverse cardiovascular events (MACE) in patients with anti-phospholipid syndrome (APS). METHOD: We included 13 947 subjects with APS from the National (Nationwide) Inpatient Sample (NIS) database for 2016-2018, and collected relevant covariates and demographic data using ICD-10 codes. Our two primary outcomes were MACE and death. We performed multivariate logistic regression analysis to assess the impact of various anti-thrombotic regimens on MACE/death in our primary cohort and high-risk subgroups. RESULTS: Patients on anti-coagulants had significantly reduced odds of MACE [odds ratio (OR) 0.68, 95% confidence interval (CI) 0.62-0.76, p < 0.001] as well as each of its subcomponents. Those not on any anti-coagulants had significantly increased odds of MACE (OR 1.47, 95% CI 1.24-1.72, p < 0.001). No significant association was found between anti-platelet use and the odds of MACE (p > 0.05). Patients on anti-coagulants were the only class that appeared to have a mortality benefit with reduced odds for death (OR 0.64, 95% CI 0.49-0.84, p = 0.001). In the subgroups at higher risk for MACE (those with atrial fibrillation and thrombocytopenia), full anti-coagulation therapy was also the only anti-thrombotic class that significantly affected the odds of MACE, with a protective effect on MACE, but had no mortality benefit. CONCLUSION: Patients with APS are most likely to benefit from anti-coagulant therapy in reducing MACE. Furthermore, anti-platelets alone or in combination with anti-coagulants are probably not beneficial in MACE reduction and may even increase risk.

Prevalence and adverse consequences of delayed diagnosis and misdiagnosis in thrombotic antiphospholipid syndrome. An observational cohort study and a review of the literature.

OBIECTIVES: This study aims to prospectively evaluate the frequency and adverse consequences of diagnostic delay and misdiagnosis in a cohort of patients with thrombotic antiphospholipid syndrome (TAPS). In addition, a systematic review of the literature concerning the diagnostic delay and misdiagnosis of TAPS was carried out. METHODS: Patient enrollment occurred between 1999 and 2022. The study group was formed by TAPS patients whose diagnosis was delayed and those who were misdiagnosed. The control group was made up of patients who were timely and correctly diagnosed with TAPS. RESULTS: The literature review showed 42 misdiagnosed patients, 27 of them were in one retrospective cohort study and 15 in 13 case reports. One hundred sixty-one out of 189 patients (85.2%) received a timely, correct diagnosis of TAPS; 28 (14.8%) did not. The number of patients with diagnostic issues was significantly higher for the first period (1999-2010), and the number of patients with a correct diagnosis was significantly higher for the second one (2011-2022). When the clinical and laboratory characteristics of the patients with delayed diagnosis were compared with those with misdiagnosis, there was a significantly higher number of severe adverse consequences characterized by permanent disability or death in the latter group. The two most common types of misdiagnoses were systemic lupus erythematosus (6 cases, 46.1%) and cardiovascular diseases (4 cases, 30.8%). CONCLUSIONS: The study demonstrates that although knowledge about TAPS has improved over time, diagnostic delays and errors remains to be addressed as they are strongly associated to adverse consequences. Key Points •Although knowledge of thrombotic antiphospholipid syndrome has improved over time, it is still limited. •Diagnostic delay and misdiagnosis are still an important issue that remains to be addressed as they are strongly associated to adverse consequences. •The three more frequent misdiagnoses are multiple sclerosis, systemic lupus erythematosus and cardiovascular diseases.

Prevalence, risk factors, and prognosis of central nervous system manifestations in antiphospholipid syndrome.

The central nervous system (CNS) is considered as one of the most frequently affected organs in antiphospholipid syndrome (APS). This study investigated the prevalence of CNS manifestations in APS and associated risk factors and evaluated stroke recurrence. We carried out this retrospective study from 2009 to 2021 at Peking University People's Hospital, which enrolled 342 APS patients, and 174 neurologic events were suffered by 119 patients (34.8%). Patients with and without CNS involvement were compared regarding demographics and laboratory parameters. The analysis showed that older age, livedo reticularis, and dyslipidaemia were significant related factors for CNS manifestations (P = 0.047, 0.038, and 0.030 respectively). The use of anticoagulants (P = 0.004), and/or hydroxychloroquine (P = 0.016) appeared to associated with a lower incidence of CNS manifestations. During a median follow-up of 4.1 years, 10 individuals developed new episodes of stroke in APS patients with previous ischemic strokes. Livedo reticularis, smoking and male gender may predict the risk of recurrent stroke (P = 0.020, 0.006, and 0.026 respectively). Collectively, our results indicated the protective and risk factors for CNS manifestations, as well as demonstrated that APS patients appeared at high risk of stroke recurrence despite current therapy.

Pregnancy outcomes in 1869 pregnancies in a large cohort from the Spanish Society of Rheumatology Lupus Register (RELESSER).

INTRODUCTION: Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population. OBJECTIVE: To assess pregnancy outcomes in women with SLE from the RELESSER cohort after 12 years of follow-up. METHODS: A multicentre retrospective observational study was conducted. In addition to data from the RELESSER register, data were collected on obstetric/gynaecological variables and treatments received. The number of term pregnancies was compared between women with pregnancies before and after the diagnosis of SLE. Further, clinical and laboratory characteristics were compared between women with pregnancies before and after the diagnosis, on the one hand, and with and without complications during pregnancy, on the other. Bivariate and multivariate analyses were carried out to identify factors potentially associated with complications during pregnancy. RESULTS: A total of 809 women were included, with 1869 pregnancies, of which 1395 reached term. Women with pregnancies before the diagnosis of SLE had more pregnancies (2.37 vs 1.87) and a higher rate of term pregnancies (76.8% vs 69.8%, p < 0.001) compared to those with pregnancies after the diagnosis. Women with pregnancies before the diagnosis were diagnosed at an older age (43.4 vs 34.1 years) and had more comorbidities. No differences were observed between the groups with pregnancies before and after diagnosis in antibody profile, including anti-dsDNA, anti-Sm, anti-Ro, anti-La, lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein. Overall, 114 out of the 809 women included in the study experienced complications during pregnancy, including miscarriage, preeclampsia/eclampsia, foetal death, and/or preterm birth. Women with complications had higher rates of antiphospholipid syndrome (40.5% vs 9.9%, p < 0.001) and higher rates of positivity for IgG anticardiolipin (33.9% vs 21.3%, p = 0.005), IgG anti-beta 2 glycoprotein (26.1% vs 14%, p = 0.007), and IgM anti-beta 2 glycoprotein (26.1% vs 16%, p = 0.032) antibodies, although no differences were found regarding lupus anticoagulant. Among the treatments received, only heparin was more commonly used by women with pregnancy complications. We did not find differences in corticosteroid or hydroxychloroquine use. CONCLUSIONS: The likelihood of term pregnancy is higher before the diagnosis of SLE. In our cohort, positivity for anticardiolipin IgG and anti-beta-2- glycoprotein IgG/IgM, but not lupus anticoagulant, was associated with a higher risk of poorer pregnancy outcomes.

Correlation of placental lesions in patients with systemic lupus erythematosus, antiphospholipid syndrome and non-criteria obstetric antiphospholipid syndrome and adverse perinatal outcomes.

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

Prevalence and diagnostic value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome in Chinese patients.

Background: The presence of antiphospholipid antibodies (aPLs) plays a pivotal role in the pathogenesis of antiphospholipid antibody syndrome (APS). This study aimed to examine the diagnostic value of a set of non-criteria aPLs and their relevance with APS-related criteria and extra-criteria manifestations. Methods: From a prospectively constructed database, consecutive APS patients consisting of 114 primary APS (PAPS group), 54 with APS secondary to SLE (SAPS group), 9 seronegative APS (SNAPS), as well as 209 patients with systemic lupus erythematosus (SLE) and 88 healthy controls were included in this study. Levels of criteria aPLs, baseline information, and APS-related criteria and extra-criteria features were extracted from the database. Serum levels of non-criteria aPLs including aPC IgG/IgM, aPI IgG/IgM, aPE IgG/IgM/IgA, aPG IgG/IgM/IgA, anti-phosphatidic acid (aPA) IgG/IgM, aSM IgG/IgM, and aPS/PT IgG/IgM were analyzed with AESKULISA® ELISA Test Kits. Results: The addition of aPC IgG/M, aPI IgG/M, aPE IgG/M/A, aSM IgG/M, and aPA IgG/M to aCL or aß2GPI IgG/M could significantly increase diagnostic sensitivity and accuracy. A significant difference between PAPS or SAPS and HC was presented in all non-criteria aPLs except for aSM IgM and aPG IgA. Eight out of nine SNAPS patients were positive for at least 1 aPL. Pregnancy morbidity was associated with aSM IgM (r = 0.22) and aSM IgG (r = 0.15). Pre-eclampsia or premature birth was associated with aSM IgG (r = 0.16), aPI IgG (r = 0.22), aPC IgG (r = 0.16), and aPG IgG (r = 0.18). Stroke was associated with aPI IgG (r = 0.2). The clinical association was also observed in DVT with aPS/PT IgG (r = 0.17). Valve lesion was positively associated with aSM IgM (Fisher test p = 0.039), APS nephropathy was associated with aPC IgG (OR 3.797), and livedo reticularis was associated with aPE IgM (OR 15.391). Conclusion: Additional detection of non-criteria aPLs including aPC IgG/M, aPE IgG/M/A, aPI IgG/M, aSM IgG/M, and aPA IgG/M could assist in APS diagnosis. The positivity of certain aPLs was statistically associated with both criteria and extra-criteria APS clinical manifestations.

Low complement levels are related to poor obstetric outcomes in women with obstetric antiphospholipid syndrome. The EUROAPS Registry Study Group.

INTRODUCTION: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease related to antiphospholipid antibodies (aPL) with primaryinflammatory injury followed by clot cascade activation and thrombus formation. Complement system activation and their participation in aPL-related thrombosis is unclosed. METHODS: We haveanalysed adverse pregnancy outcomes (APO) related to low complement (LC) levels in a cohort of 1048 women fulfilling classification criteria for OAPS. RESULTS: Overall, 223 (21.3%) women presented LC values, during pregnancy. The length of pregnancy was shorter in OAPS women with LC compared to those with normal complement (NC) (median: 33 weeks, interquartile range: [24-38] vs. 35 weeks [27-38]; p = 0.022). Life new-born incidence was higher in patients with NC levels than in those with LC levels (74.4% vs. 67.7%; p = 0.045). Foetal losses were more related to women with triple or double aPL positivity carrying LC than NC values (16.3% vs. 8.0% NC; p = 0.027). Finally, some placental vasculopathies were affected in OAPS patients with LC as late Foetal Growth Restriction (FGR >34 weeks) rise to 7.2% in women with LC vs. 3.2% with NC (p = 0.007). DISCUSSION: Data from our registry indicate that incidence of APO was higher in OAPS women with LC levels and some could be reverted by the correct treatment.