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In the original article, the affiliation of co-author Cecilia Beatrice Chighizola should have read: “Experimental Laboratory of Immunological and Rheumatologic Researches, Istituto Auxologico Italiano, IRCCS, Cusano Milanino, Milan, Italy”. These details have been corrected only in this corrigendum to preserve the published version of record.

Objectives To compare clinical features, laboratory data and fetal-maternal outcomes between 1000 women with obstetric APS (OAPS) and 640 with aPL-related obstetric complications not fulfilling Sydney criteria (non-criteria OAPS, NC-OAPS). Methods This was a retrospective and prospective multicentre study from the European Registry on Obstetric Antiphospholipid Syndrome. Results A total of 1650 women with 5251 episodes, 3601 of which were historical and 1650 latest episodes, were included. Altogether, 1000 cases (OAPS group) fulfilled the Sydney classification criteria and 650 (NC-OAPS group) did not. Ten NC-OAPS cases were excluded for presenting thrombosis during follow-up. All cases were classified as category I (triple positivity or double positivity for aPL) or category II (simple positivity). Overall, aPL laboratory categories showed significant differences: 29.20% in OAPS vs 17.96% in NC-OAPS (P < 0.0001) for category I, and 70.8% in OAPS vs 82% in NC-OAPS (P < 0.0001) for category II. Significant differences were observed when current obstetric complications were compared (P < 0.001). However, major differences between groups were not observed in treatment rates, livebirths and thrombotic complications. In the NC-OAPS group, 176/640 (27.5%) did not fulfil Sydney clinical criteria (subgroup A), 175/640 (27.34%) had a low titre and/or non-persistent aPL positivity but did meet the clinical criteria (subgroup B) and 289/640 (45.15%) had a high aPL titre but did not fulfil Sydney clinical criteria (subgroup C). Conclusion Significant clinical and laboratory differences were found between groups. Fetal-maternal outcomes were similar in both groups when treated. These results suggest that we could improve our clinical practice with better understanding of NC-OAPS patients.

Coronavirus disease-2019 (COVID-19) related to Coronavirus-2 (SARS-CoV-2) is a worldwide health concern. Despite the majority of patients will evolve asymptomatic or mild-moderate upper respiratory tract infections, 20% will develop severe disease. Based on current pathogenetic knowledge, a severe COVID-19 form is mainly a hyperinflammatory, immune-mediated disorder, triggered by a viral infection. Due to their particular immunological features, pregnant women are supposed to be particularly susceptible to complicate by intracellular infections as well as immunological disturbances. As an example, immune-thrombosis has been identified as a common immune-mediated and pathogenic phenomenon both in COVID-19, in obstetric diseases and in COVID-19 pregnant women. According to extensive published clinical data, is rationale to expect an interference with the normal development of pregnancy in selected SARS-CoV-2-infected cases, mainly during third trimester. This manuscript provides insights of research to elucidate the potential harmful responses to SARS-CoV-2 and /or other coronavirus infections, as well as bidirectional interactions between COVID-19 and pregnancy to improve their respective management.

Objectives. To compare clinical features, laboratory data and fetal-maternal outcomes between 1000 women with obstetric APS (OAPS) and 640 with aPL-related obstetric complications not fulfilling Sydney criteria (non-criteria OAPS, NC-OAPS). Methods. This was a retrospective and prospective multicentre study from the European Registry on Obstetric Antiphospholipid Syndrome. Results. A total of 1650 women with 5251 episodes, 3601 of which were historical and 1650 latest episodes, were included. Altogether, 1000 cases (OAPS group) fulfilled the Sydney classification criteria and 650 (NC-OAPS group) did not. Ten NC-OAPS cases were excluded for presenting thrombosis during follow-up. All cases were classified as category I (triple positivity or double positivity for aPL) or category II (simple positivity). Overall, aPL laboratory categories showed significant differences: 29.20% in OAPS vs 17.96% in NC-OAPS (P < 0.0001) for category I, and 70.8% in OAPS vs 82% in NC-OAPS (P < 0.0001) for category II. Significant differences were observed when current obstetric complications were compared (P < 0.001). However, major differences between groups were not observed in treatment rates, livebirths and thrombotic complications. In the NC-OAPS group, 176/640 (27.5%) did not fulfil Sydney clinical criteria (subgroup A), 175/640 (27.34%) had a low titre and/or non-persistent aPL positivity but did meet the clinical criteria (subgroup B) and 289/640 (45.15%) had a high aPL titre but did not fulfil Sydney clinical criteria (subgroup C). Conclusion. Significant clinical and laboratory differences were found between groups. Fetal-maternal outcomes were similar in both groups when treated. These results suggest that we could improve our clinical practice with better understanding of NC-OAPS patients.

Preeclampsia is caused by placental impairment with increased expression of sFlt-1 (soluble fms-like tyrosine kinase 1) and decreased PlGF (placental growth factor); it has been associated with cardiovascular morbidity and mortality later in life, but the underlying mechanism remains unknown. The aim of this study was to determine whether sFlt-1 and PlGF levels during preeclampsia are associated to long-term cardiovascular risk. We prospectively recruited 43 women with previous preeclampsia and 21 controls with uncomplicated pregnancies. Cardiovascular risk assessment approximate to 12 years later included maternal hemodynamic, cardiac function and structure, biomarker analysis, and carotid-intima thickness evaluation. Women with previous preeclampsia had higher prevalence of hypertensive disorders and dyslipidemia than controls. In addition, they had worse global longitudinal strain, thicker left ventricular septal and posterior walls, more myocardial mass and increased carotid intima-media thickness compared with controls. PlGF during pregnancy correlated positively with high-density lipoprotein (r=0.341; P=0.006), and negatively with global longitudinal strain (r=-0.581; P

Background: No absolute data on the treatment of antiphospholipid antibodies (aPL) related to refractory obstetric complications exist to date. TNF-alpha play a major role in this disorder. Objective: To assess the effectiveness of TNF-alpha blockers in 18 aPL-positive women with recurrent infertility after therapy with low-molecular-weight heparin (LMWH) plus aspirin (LDA) plus hydroxychloroquine (HCQ). Methods: Prospective case-series of 12 women fulfilling Sydney criteria for obstetric antiphospholipid syndrome (OAPS) and 6 with incomplete forms (OMAPS). All women tested positive for aPL at least twice. Non criteria aPL were tested in 15/18. Complement, TNF-alpha and IL-10 were also evaluated. Women were closely monitored for fetal well-being and possible malformations throughout gestation and the postpartum period. Results: Sixteen patients were started on adalimumab and 2 on certolizumab. Twelve women completed gestation: 9 at term and 3 pre-term. Differences in laboratory categories and outcomes were observed when OAPS and OMAPS were compared. First trimester miscarriage or implantation failure recurred in 6 cases, all of the OAPS group. Malformations were not seen in the newborns. Conclusions: Overall, good obstetric results were obtained in 70% of previous LMWH-LDA+HCQ refractory cases. TNF-alpha blockers were well tolerated without adverse effects. The combination of LMWH plus LDA plus TNF-alpha blockers appears to be a promising treatment for refractory obstetric complaints related to aPL; nevertheless, outcome differences between OAPS and OMAPS do exist. (C) 2019 Published by Elsevier Inc.

Aim: To analyse the clinical features, laboratory data and foetal-maternal outcomes, and follow them up on a cohort of 1000 women with obstetric antiphospholipid syndrome (OAPS). Methods: The European Registry of OAPS became a registry within the framework of the European Forum on Antiphospholipid Antibody projects and was placed on a website in June 2010. Thirty hospitals throughout Europe have collaborated to carry out this registry. Cases with obstetric complaints related to antiphospholipid antibodies (aPL) who tested positive for aPL at least twice were included prospectively and retrospectively. The seven-year survey results are reported. Results: 1000 women with 3553 episodes were included of which 2553 were historical and 1000 were latest episodes. All cases fulfilled the Sydney classification criteria. According to the laboratory categories, 292 (29.2%) were in category I, 357 (35.7%) in IIa, 224 (22.4%) in IIb and 127 (12.7%) in IIc. Miscarriages were the most prevalent clinical manifestation in 386 cases (38.6%). Moreover, the presence of early preeclampsia (PE) and early foetal growth restriction (FGR) appeared in 181 (18.1%) and 161 (16.1%), respectively. In this series, 448 (44.8%) women received the recommended OAPS treatment. Patients with recommended treatment had a good live-birth rate (85%), but worse results (72.4%) were obtained in patients with any treatment (low-dose aspirin (LDA) or low-molecular-weight heparin (LMWH) not on recommended schedule, while patients with no treatment showed a poor birth rate (49.6%). Conclusion: In this series, recurrent miscarriage is the most frequent poor outcome. To avoid false-negative diagnoses, all laboratory category subsets were needed. OAPS cases have very good foetal-maternal outcomes when treated. Results suggest that we were able to improve our clinical practice to offer better treatment and outcomes to OAPS patients.

Aim: To analyse the clinical features, laboratory data and foetal-maternal outcomes, and follow them up on a cohort of 1000 women with obstetric antiphospholipid syndrome (OAPS). Methods: The European Registry of OAPS became a registry within the framework of the European Forum on Antiphospholipid Antibody projects and was placed on a website in June 2010. Thirty hospitals throughout Europe have collaborated to carry out this registry. Cases with obstetric complaints related to antiphospholipid antibodies (aPL) who tested positive for aPL at least twice were included prospectively and retrospectively. The seven-year survey results are reported. Results: 1000 women with 3553 episodes were included of which 2553 were historical and 1000 were latest episodes. All cases fulfilled the Sydney classification criteria. According to the laboratory categories, 292 (29.2%) were in category I, 357 (35.7%) in Era, 224 (22.4%) in IIb and 127 (12.7%) in IIc. Miscarriages were the most prevalent clinical manifestation in 386 cases (38.6%). Moreover, the presence of early preeclampsia (PE) and early foetal growth restriction (FGR) appeared in 181 (18.1%) and 161 (16.1%), respectively. In this series, 448 (44.8%) women received the recommended OAPS treatment. Patients with recommended treatment had a good live-birth rate (85%), but worse results (72.4%) were obtained in patients with any treatment (low-dose aspirin (LDA) or low-molecular-weight heparin (LMWH) not on recommended schedule, while patients with no treatment showed a poor birth rate (49.6%). Conclusion: In this series, recurrent miscarriage is the most frequent poor outcome. To avoid false-negative diagnoses, all laboratory category subsets were needed. OAPS cases have very good foetal-maternal outcomes when treated. Results suggest that we were able to improve our clinical practice to offer better treatment and outcomes to OAPS patients.

To ascertain whether screening for pre-eclampsia (PE) and intrauterine growth restriction (IUGR) by uterine artery (UtA) Doppler in the second trimester of pregnancy and targeted surveillance improve maternal and perinatal outcomes in an unselected population.This was a multicenter randomized open-label controlled trial. At the routine second-trimester anomaly scan, women were assigned randomly to UtA Doppler or non-Doppler groups. Women with abnormal UtA Doppler were offered intensive surveillance at high-risk clinics of the participating centers with visits every 4 weeks that included measurement of maternal blood pressure, dipstick proteinuria, fetal growth and Doppler examination. The primary outcome was a composite score for perinatal complications, defined as the presence of any of the following: PE, IUGR, spontaneous labor37 weeks' gestation, placental abruption, stillbirth, gestational hypertension, admission to neonatal intensive care unit and neonatal complications. Secondary outcomes were a composite score for maternal complications (disseminated intravascular coagulation, maternal mortality, postpartum hemorrhage, pulmonary edema, pulmonary embolism, sepsis), and medical interventions (for example, corticosteroid administration and induction of labor) in patients developing placenta-related complications.In total, 11 667 women were included in the study. Overall, PE occurred in 348 (3.0%) cases, early-onset PE in 48 (0.4%), IUGR in 722 (6.2%), early-onset IUGR in 93 (0.8%) and early-onset PE with IUGR in 32 (0.3%). UtA mean pulsatility index90(th) percentile was able to detect 59% of early-onset PE and 60% of early-onset IUGR with a false-positive rate of 11.1%. When perinatal and maternal data according to assigned group (UtA Doppler vs non-Doppler) were compared, no differences were found in perinatal or maternal complications. However, screened patients had more medical interventions, such as corticosteroid administration (relative risk (RR), 1.79 (95% CI, 1.4-2.3)) and induction of labor for IUGR (RR, 1.36 (95% CI, 1.07-1.72)). In women developing PE or IUGR, there was a trend towards fewer maternal complications (RR, 0.46 (95% CI, 0.19-1.11)).Routine second-trimester UtA Doppler ultrasound in an unselected population identifies approximately 60% of women at risk for placental complications; however, application of this screening test failed to improve short-term maternal and neonatal morbidity and mortality. Copyright © 2016 ISUOG. Published by John WileySons Ltd.

The co-existence of inherited thrombophilia with antiphospholipid antibody (aPL) positivity is not uncommon. This association does not overrule the diagnosis of antiphospholipid syndrome. Infection may present together with transient aPL positivity, usually aCL-IgM isotype. Thus certain infections, virus particularly, may increase “per se” thrombotic risk. Herein, we communicate the case of a 29-year-old man who sought medical attention because of a ten days course left-side abdominal pain, cough, fever, fatigue, arthralgia and mild dyspnoea. The patient was diagnosed of multiple pulmonary and splenic infarcts. Interestingly, laboratory results showed the presence of JAK2- V617F mutation, positive CMV serology, first IgM and IgG further, as well as LA test and aCL-IgM transiently but recurrently positive. The role played by these aPL transiently positive antibodies – laboratory category I – as a trigger in the development of this thrombotic diathesis is being discussed.

Background:. An increasing number of persons seek medical solutions for esthetic indications and for diverse pathological conditions, such as malformations, trauma, or cancer. Despite manufacturers' and different authors' claims that fillers are non-immunogenic or that complications are uncommon, unwanted adverse reactions do occur. Objectives: To review the literature regarding the multiple types of immune-mediated adverse reactions related to medical dermal filler injections/prosthesis. Methods: A comprehensive MEDLINE, PubMed, and Google Scholar electronic database search was performed (2000-January 2012). Selected articles published before 2000 referring to general concerns regarding the studied topic were also included. The search provided almost 300 articles. Finally, 235 studies were selected and included. Results: All known fillers present in the market have been shown to be able to provoke early- and late-onset inflammatory adverse reactions. Their true prevalence is unknown but appears to be significant. The majority of the late-onset adverse effects are inflammatory and immune-mediated in nature. Edema, granulomas, sarcoid-like disorders, and panniculitis are the findings most commonly seen. Rarely, systemic granulomatous and autoimmune diseases, and to lesser extent acute hypersensitivity reactions can be seen. Conclusions: All implanted, injected, and blood-contact biomaterials trigger a wide variety of adverse reactions that may appear early or late and range from local to systemic. Most fillers act more as adjuvants than as direct T-cell activators, on a background of genetic predisposition. Their treatment has not been the subject of well-designed studies. Management of both acute and systemic reactions is often difficult and requires anti-inflammatory and occasionally immunosuppressive therapy. (C) 2013 Elsevier Inc. All rights reserved.

An ever-increasing number of persons seek medical solutions to improve the appearance of their aging skin or for aesthetic and cosmetic indications in diverse pathological conditions, such as malformations, trauma, cancer, and orthopedic, urological, or ophthalmological conditions. Currently, physicians have many different types of dermal and subdermal fillers, such as non-permanent, permanent, reversible, or non-reversible materials. Despite the claims of manufacturers and different authors that fillers are non-toxic and non-immunogenic or that complications are very uncommon, unwanted side effects do occur with all compounds used. Implanted, injected, and blood-contact biomaterials trigger a wide variety of adverse reactions, including inflammation, thrombosis, and excessive fibrosis. Usually, these adverse reactions are associated with the accumulation of large numbers of mononuclear cells. The adverse reactions related to fillers comprise a broad range of manifestations, which may appear early or late and range from local to systemic. Clinicians should be aware of them since the patient often denies the antecedent of injection or is unaware of the material employed. Most of these adverse effects seem to have an immunological basis, the fillers acting more as adjuvants than as direct T-cell activators, on a background of genetic predisposition. Their treatment has not been the subject of well-designed studies; management of both acute and systemic reactions is often difficult, and requires anti-inflammatory and occasionally immunosuppressive therapy. The clinical, pathological, and therapeutic aspects of inflammatory and immune-mediated late-onset adverse reactions related to soft tissue filler injections are thoroughly reviewed herein.

COVID-19; Inflammation; Soft tissue fillers COVID-19; Inflamación; Rellenos de tejidos blandos COVID-19; Inflamació; Farciments de teixits tous Background Adverse events (AE) after COVID-19 vaccines, particularly, but not solely, with those messenger RNA (mRNA)-based vaccines, have rarely been reported in patients previously treated with dermal fillers (DF). Objective To evaluate the morphology, clinical characteristics, the timing of presentation, and outcomes of inflammatory AE appeared in patients injected with DF, after anti-COVID-19 vaccination. Methods Descriptive study of a case series of 20 consecutive patients collected after the occurrence of AE in previously filled areas post COVID-19 vaccination. Results From January 2021 to July 2021, we analyzed 20 AE reactions triggered by COVID-19 vaccines in the previously mentioned cohort. They were vaccinated with Pfizer/Biontech (11; 55%), Moderna (5; 25%), Astra-Zeneca (3; 15%), and Sputnik (1; 5%). The most common manifestations were oedema/swelling, angioedema, erythema, skin induration, and granuloma. Less common reactions included myalgia and lymphadenopathy. In 13/20 (65%) cases, the AE appeared after the first dose of vaccine. These inflammatory AE appeared more rapidly after the second dose than after the first one. In 13/20 (65%) cases, the symptomatology subsided with anti-inflammatory/antihistaminic drugs, while spontaneously in 3/20 (15%). The manifestations are ongoing.in the remaining four cases (20%). Conclusion Although probably rare, both RNA-based and adenovirus-based anti-COVID-19 vaccines can cause inflammatory bouts in patients previously treated with DF. In these cases, caution should be paid on subsequent vaccine doses, considering a tailored risk/benefit for any case before next vaccination.

Objectives An increased risk of adverse maternal and foetal pregnancy complications (including pre-eclampsia, intrauterine growth restriction, and small for gestational age) is well described in women with autoimmune rheumatic disease (ARD) compared with the general population (GenPop). It is less clear, however, whether this risk of adverse pregnancy outcome (APO) also exists in women with ‘preclinical ARD’ (pre-ARD) before they are diagnosed with an ARD many years post-partum. Therefore, we have undertaken a systematic review of the available evidence on APO in patients who subsequently were diagnosed with a rheumatic disease to identify whether there is an increased risk in pre-ARD. Methods The present study was reported in accordance with the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. A systematic literature review was performed using the online PubMed database. Pre-SLE and pre-RA patients were defined as those who, over the subsequent years, developed SLE or RA according to international classification criteria. Results A total of 176 articles were screened, and 27 original articles were selected for final analysis. Pre-RA was the most studied group, with 15 studies and a total of >1600 pregnancies, and pre-SLE was the second-most studied pre-ARD in pregnancy, with 14 studies and a total of >1000 pregnancies. We found that patients who subsequently developed SLE had an increased burden of poor pregnancy outcomes compared with pregnant women from the GenPop, but fewer APOs compared with pregnancies of women with SLE. In contrast, a similar rate of APOs was found when pre-RA pregnancies were compared with GenPop pregnancies. Conclusion Our findings of an increased risk of APO in certain pre-ARDs highlights the relevance of taking an obstetric history during the first rheumatology appointment and the need for novel screening strategies for the prediction of APOs. Further research is required to elucidate the immune basis of APOs in preclinical and clinical ARD.

Diagnosis; Obstetric antiphospholipid syndrome; Pathogenesis Diagnóstico; Síndrome antifosfolípido obstétrico; Patogénesis Diagnòstic; Síndrome antifosfolípid obstètric; Patogènesi Antiphospholipid syndrome is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity associated with persistent antiphospholipid antibody positivity. Cases fulfilling the Sydney criteria for obstetric morbidity with no previous thrombosis are known as obstetric antiphospholipid syndrome (OAPS). OAPS is the most identified cause of recurrent pregnancy loss and late-pregnancy morbidity related to placental injury. Cases with incomplete clinical or laboratory data are classified as obstetric morbidity APS (OMAPS) and non-criteria OAPS (NC-OAPS), respectively. Inflammatory and thrombotic mechanisms are involved in the pathophysiology of OAPS. Trophoblasts, endothelium, platelets and innate immune cells are key cellular players. Complement activation plays a crucial pathogenic role. Secondary placental thrombosis appears by clot formation in response to tissue factor activation. New risk assessment tools could improve the prediction of obstetric complication recurrences or thromboses. The standard-of-care treatment consists of low-dose aspirin and prophylactic low molecular weight heparin. In refractory cases, the addition of hydroxychloroquine, low-dose prednisone or IVIG improve pregnancy outcomes. Statins and eculizumab are currently being tested for treating selected OAPS women. Finally, we revisited recent insights and concerns about the pathophysiology, diagnosis and management of OAPS. This study was supported, in part, by a grant from the Ona Futura Foundation, Balearic Islands (ONA-JAR-2021), Spain and from the International Center for Human Assisted Reproduction of Barcelona (GRAVIDA, GRA-JAR-2021), Spain.

Angiogenic factors; Preeclampsia; Uric acid Factores angiogénicos; Preeclampsia; Ácido úrico Factors angiogènics; Preeclàmpsia; Àcid úric N-terminal pro-brain natriuretic peptide (NT-proBNP) and uric acid are elevated in pregnancies with preeclampsia (PE). Short-term prediction of PE using angiogenic factors has many false-positive results. Our objective was to validate a machine-learning model (MLM) to predict PE in patients with clinical suspicion, and evaluate if the model performed better than the sFlt-1/PlGF ratio alone. A multicentric cohort study of pregnancies with suspected PE between 24+0 and 36+6 weeks was used. The MLM included six predictors: gestational age, chronic hypertension, sFlt-1, PlGF, NT-proBNP, and uric acid. A total of 936 serum samples from 597 women were included. The PPV of the MLM for PE following 6 weeks was 83.1% (95% CI 78.5-88.2) compared to 72.8% (95% CI 67.4-78.4) for the sFlt-1/PlGF ratio. The specificity of the model was better; 94.9% vs. 91%, respectively. The AUC was significantly improved compared to the ratio alone [0.941 (95% CI 0.926-0.956) vs. 0.901 (95% CI 0.880-0.921), p < 0.05]. For prediction of preterm PE within 1 week, the AUC of the MLM was 0.954 (95% CI 0.937-0.968); significantly greater than the ratio alone [0.914 (95% CI 0.890-0.934), p < 0.01]. To conclude, an MLM combining the sFlt-1/PlGF ratio, NT-proBNP, and uric acid performs better to predict preterm PE compared to the sFlt-1/PlGF ratio alone, potentially increasing clinical precision. This work was supported by public funds obtained in competitive calls with peer review (grant PI19/00702), Insituto de Salud Carlos III, Spanish Ministry of Health, by the Maternal and Child Health and Development Network (SAMID, RD16/0022/0015), Instituto de Salud Carlos III, Madrid, Spain, the Spanish Clinical Research and Clinical Trials Platform, SCReN (Spanish Clinical Research Network), funded by the ISCIII-General Subdirectorate for Evaluation and Promotion of Research, through project PT13/0002/0028, integrated in the 2013–2016 R + D + I State Plan and co-financed by and the European Regional Development Fund (FEDER); and by the Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin Network (RICORS, RD21/0012/0001), Instituto de Salud Carlos III, Madrid, Spain, funded by the Recovery, Transformation and Resilience Plan 2017–2020, ISCIII, and by the European Union-Next Generation EU. Dr Cruz-Lemini is supported by Juan Rodés contract JR19/00047, Instituto de Salud Carlos III-Spanish Ministry of Health. Funding sources were not involved in study design, collection, analysis, and interpretation of data.

Antiphospholipid antibodies; Obstetric antiphospholipid syndrome; Thrombotic antiphospholipid syndrome Anticuerpos antifosfolípidos; Síndrome antifosfolípido obstétrico; Síndrome antifosfolípido trombótico Anticossos antifosfolípids; Síndrome antifosfolípid obstètric; Síndrome antifosfolípid trombòtic Antiphospholipid syndrome (APS) is a systemic autoimmune condition characterised by the presence of antiphospholipid antibodies (aPL) associated with vascular thrombosis and/or pregnancy complications. In a cohort of 74 yet diagnosed APS individuals fulfilling Sydney laboratory criteria (twice positive for lupus anticoagulant, anticardiolipin, aCL, and/or anti-β2glycoprotein I, aβ2GPI), 33 out of 74 were obstetric APS (OAPS) and 41 thrombotic APS (TAPS) patients. 39% of TAPS patients were women. Although aPL detection was persistent, we observed an oscillatory aPL positivity in 56.7% and a transient seroconversion in 32.4% of APS patients at enrolment. Thus, we tested their sera in a line immunoassay that simultaneously detected IgG or IgM for criteria (aCL and aβ2GPI) and non-criteria (anti-phosphatidylserine, aPS; anti-phosphatidic acid, aPA; anti-phosphatidylinositol, aPI; anti-annexin 5, aA5; anti-prothrombin, aPT; anti-phosphatidylethanolamine; anti-phosphatidylglycerol, and anti-phosphatidylcholine) aPL. OAPS and TAPS patients displayed different but overlapping clusters based on their aPL reactivities. Specifically, while OAPS patients showed higher aPA, aPS, aA5, aβ2GPI and aPT IgM levels than TAPS patients, the latter displayed higher reactivity in aCL, aPI and aA5 IgG. Eventually, with a cut-off of the 99th percentile established from a population of 79 healthy donors, TAPS patients significantly tested more positive for aCL and aA5 IgG than OAPS patients, who tested more positive for aPA, aPS and aβ2GPI IgM. Transiently seronegative APS patients showed non-criteria aPL positivity twice in sera obtained 3 months apart. Overall, our data show that APS patients presented clusters of aPL that define different profiles between OAPS and TAPS, and persistent non-criteria aPL positivity was observed in those who are transiently seronegative. This research was funded by Fundació Ona Futura (ONA-JAR-2021; Port d’Alcudia, Balearic Islands, Spain); and Gravida Fertilitat Avançada (GRA-JAR-2021; Barcelona, Spain).

BACKGROUND The combination of low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH) until the end of gestation are the currently the accepted standard of care for the treatment of antiphospholipid-related obstetric disorders. In refractory cases, hydroxychloroquine (HCQ) can be added to this standard of care. OBJECTIVE To evaluate the haemostatic safety of LDA and LMWH (medium to high prophylactic doses) during pregnancy and the puerperium in women with both full-blown obstetric antiphospholipid syndrome (OAPS) (Sydney criteria) and noncriteria - incomplete - OAPS. STUDY DESIGN Retrospective/prospective multicentre observational study. Obstetric background, laboratory categories, delivery mode, antithrombotic regimens and bleeding complications were compared. SETTING A total of 30 tertiary European hospitals. PATIENTS Mainly, Caucasian/Arian pregnant women were included. Other ethnicities were minimally present. Women were controlled throughout pregnancy and puerperium. MAIN OUTCOME MEASURES The primary end-point was to evaluate the number of major and minor haemorrhagic complications in this cohort of women. Neuraxial anaesthetic bleeding complications were particularly assessed. Secondly, we aimed to compare local/general bleeding events between groups. RESULTS We studied 1650 women, of whom 1000 fulfilled the Sydney criteria of the OAPS and 650 did not (noncriteria OAPS). Data on antithrombotic-related complications were available in 1075 cases (65.15%). Overall, 53 (4.93%) women had bleeding complications, with 34 being considered minor (3.16%) and 19 major (1.76%). Neither obstetric complications nor laboratory categories were bleeding-related. Assisted vaginal delivery and caesarean section were related to local haemorrhage. Heparin doses and platelet count were not associated with major bleeding. CONCLUSIONS LDA and medium to high prophylactic LMWH during pregnancy in women with full-blown OAPS/noncriteria OAPS are safe. A slight increase in bleeding risk was noted in instrumental deliveries. No women who underwent spinal or epidural anaesthesia suffered bleeding complications. No haemorrhage was observed in cases where HCQ was added to standard therapy.

To analyse the clinical features, laboratory data, foetal-maternal outcomes, and follow-up in a cohort of 247 women with obstetric antiphospholipid syndrome (OAPS).The European Registry on APS became a Registry within the framework of the European Forum on Antiphospholipid Antibody projects and placed on a website in June 2010. Cases with obstetric complaints related to aPL who tested positive for aPL prospectively and retrospectively were included. The three-year survey results are reported.338 women with 1253 pregnancy episodes were included; 915 were historical and 338 were latest episodes. All these women tested positive for aPL. 247 of the 338 fulfilled the Sydney criteria. According to the laboratory categories, 84/247 were in category I, 42 in IIa, 66 in IIb and 55 in IIc. Obstetric complications other than foetal losses, appeared in 129 cases (52.2%). 192 (77.7%) had a live birth and 55 (22.3%) did not. The latter group of only 38 cases (69%) received adequate treatment and 17 (31%) did not. 177/247 (72%) women were put on heparin plus LDA. Thrombosis appeared in two during pregnancy and in 14 during the puerperium. 7 (3%) women evolved to complete SLE.OAPS shows differential characteristics than classical APS. All laboratory test categories are needed to avoid false-negative diagnoses. In some cases, complement levels could act as a serological marker. OAPS has very good foetal-maternal outcomes when treated. Thrombosis and progression to SLE in mothers with OAPS are scarce compared with "classical APS", suggesting that they have different aPL-mediated pathogenic mechanisms.