Antiphospholipid Syndrome Research Articles

Thrombotic Microangiopathy in the Postpartum Period (Literature Review, Clinical Case Report)

Introduction. Thrombotic microangiopathy (TMA) is a heterogeneous group of diseases that, in the presence of endothelial damage, can lead to microvascular thrombosis, secondary platelet consumption, mechanical hemolysis and ischemic end-organs damage. Such triad of symptoms as acute kidney injury (AKI), microangiopathic hemolysis and thrombocytopenia may also accompany some pregnancy-specific conditions (severe preeclampsia/HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count), acute fatty liver disease of pregnancy (AFLP), and conditions not related to pregnancy, but triggered by it (catastrophic antiphospholipid syndrome (CAPS), lupus flare. The aim of the study. To review the current literature devoted to the problem of thrombotic microangiopathy, to demonstrate on a clinical case a step-by-step differentiated approach to the diagnosis of the type of thrombotic microangiopathy causing acute kidney injury in the postpartum period, and to describe modern methods of treatment of these diseases. Results. The classical types of TMA are thrombotic thrombocytopenic purpura (TTP) and typical hemolytic uremic syndrome (HUS), also known as enterohemorrhagic Shiga toxin-producing Escherichia coli (STEC)-associated HUS (STEC-HUS). Pathophysiologically, all forms of TMA involve complement-mediated endothelial cell damage, which mainly affects the capillary zone of the kidney. Pregnancy can trigger atypical HUS (aHUS) or TTP. The article describes the clinical case of a 37-year-old woman who developed AKI following a complicated delivery. A turn-based differential diagnosis of aHUS was performed. Unwarranted discontinuation of the targeted therapy with Eculisumab led to the development of chronic renal failure Conclusions. Thrombotics microangiopathy are the life-threatening conditions rarely seen in pregnancy making its early recognition difficult. As thrombotics microangiopathy require urgent treatment, plasmapheresis should be started as soon as they are suspected, followed by targeted therapy (Eculisumab, Rituximab) after the confirmation of the diagnosis. This may contribute to reducing maternal morbidity and mortality rates.

Absence of platelet overactivation and thrombosis formation among patients with coronary atherosclerosis disease after vaccination against SARS-CoV-2

BackgroundAssociation of Coronavirus disease 2019 vaccines with thrombosis has raised concerns among patients with coronary atherosclerosis disease (CAD). ObjectivesAfter vaccination against SARS-CoV-2, to detect thrombosis formation in atherosclerosis ApoE−/− mice, and platelet activation, coagulation, the profile of prothrombotic antibodies, and the production of platelet factor 4 (PF4) antibodies in patients with CAD. MethodsAtherosclerotic ApoE−/− mice were immunized with saline or inactivated SARS-CoV vaccines. We investigated FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo. Inpatients undergoing percutaneous coronary intervention (PCI) were consecutively enrolled and defined according to vaccination status. We evaluated coagulation by thrombelastograph (TEG), platelet activation makers by flow cytometry, PF4 antibody and antiphospholipid antibodies by ELISA, and SARS-CoV-2 neutralizing antibody. ResultsIn atherosclerotic ApoE−/− mice, FeCl3-induced thrombus formation and thrombus formation under flow conditions were similar between saline-treated and inactivated SARS-CoV-2 vaccines-treated groups. A total of 182 patients undergoing PCI were included in the final analysis, of whom 92 had been vaccinated. Baseline characteristics were well balanced between unvaccinated and vaccinated groups. The expression of PAC-1 and P-selectin, the prevalence of positivity for PF4 antibodies and antiphospholipid antibodies were similar between these two groups. ConclusionsInactivated SARS-CoV-2 vaccines did not potentiate thrombosis formation in atherosclerotic mice. Inactivated SARS-CoV-2 vaccines did not enhance platelet activation, or trigger the production of PF4 and antiphospholipid antibodies in patients with CAD. In light of the observed thrombotic risks associated with adenovirus-based COVID-19 vaccines, inactivated vaccines may offer a potentially safer option for individuals with CAD.

The role of anticoagulation on the long-term survival of patients with pulmonary arterial hypertension: A meta-analysis of 15 cohort studies

IntroductionAnticoagulation was once recommended for patients with pulmonary arterial hypertension (PAH). However, its survival benefit still remained controversial. We performed a meta-analysis to evaluate the effect of anticoagulation on the long-term survival of PAH patients. MethodsThe PubMed, EMBASE, Web of Science, and WanFang electronic database were searched for eligible studies. Pooled hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated for effect estimate regarding anticoagulation on the survival of PAH patients. ResultsFifteen cohort studies involving 4266 PAH patients were included. Approximately 45.8 % patients received anticoagulation. The mean follow-up period ranged from 2.1 to 14 years. Anticoagulation had a tendency to, however, did not significantly reduce mortality of PAH patients (HR: 0.86, 95 % CI: 0.73–1.02). In subgroup analysis, anticoagulation decreased the mortality risk as analyzed from retrospective studies (HR: 0.80, 95 % CI: 0.65–0.98), but not prospective studies (HR: 0.95, 95 % CI: 0.70–1.29). For both idiopathic PAH (IPAH) and connective tissue disease associated PAH (CTD-PAH), anticoagulation therapy did not significantly improve the long-term survival rate (HR: 0.83, 95 % CI: 0.65–1.07, and HR: 1.05, 95 % CI: 0.77–1.42, respectively), and this result remained unchanged when pooling data from either retrospective or prospective studies. Further analysis showed that anticoagulation had no advantage in reducing mortality in patients with systemic sclerosis associated PAH, systemic erythematosus lupus related PAH (free of antiphospholipid syndrome), or CTD-PAH of non-specified etiology. ConclusionAnticoagulation may not reduce the long-term mortality of PAH patients, including those with IPAH and CTD-PAH. In the management of PAH, anticoagulants should be prescribed with caution before comprehensive risk to benefit evaluation. Larger and more vigorously designed controlled trials are warranted.

Impact of the 2023 ACR/EULAR Classification Criteria in Women with Primary Antiphospholipid Syndrome during Pregnancy.

Background/Objectives: ACR/EULAR has recently developed new classification criteria for antiphospholipid syndrome (APS). The present study aims to analyze the impact of these new 2023 ACR/EULAR classification criteria in a cohort of pregnant women with primary APS. Methods: Retrospective cohort study of 93 consecutive pregnant women attending the Autoimmune Diseases Pregnancy Clinic, a multidisciplinary unit of a tertiary care teaching hospital, between 2005 and 2023. All of them fulfilled the Sydney classification criteria for APS. Women diagnosed with rheumatic autoimmune diseases other than APS were excluded. Results: Twenty-four out of ninety-three patients (25.8%) met the 2023 ACR/EULAR criteria for APS. Patients who met the new classification criteria were very similar to those who did not, except for being younger (p < 0.001), and had a lower number of clinical pregnancies (p = 0.004). The obstetric domain was clearly underrepresented in women who fulfilled the 2023 ACR/EULAR criteria (p < 0.001). Patients meeting the new classification criteria were primarily characterized by preterm births before 34 weeks due to severe placentation disorders (p = 0.004). Women with early and late fetal loss were significantly underrepresented (p < 0.0001 and 0.03, respectively). Nearly half of these patients had thrombocytopenia (p < 0.001). Serologically, these patients showed a higher frequency of persistent lupus anticoagulant (p = 0.02) and a lower frequency of IgM isotype antiphospholipid antibodies (p = 0.05). Conclusions: Almost three-quarters of the patients included in the study did not meet the 2023 ACR/EULAR criteria. Most patients who could not be classified according to these new classification criteria were those with early and/or late fetal deaths, as well as patients carrying only IgM aCL/AB2GPI antibodies. The high specificity of the 2023 ACR/EULAR criteria, restricted to severe placentation disorders, may leave the majority of patients with obstetric APS out of the new classification criteria.

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

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. 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. 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. 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.

Outcomes in children with provoked venous thrombosis and antiphospholipid antibodies: findings from the Kids-DOTT trial

AbstractFew studies have prospectively evaluated the incidence and outcomes in children with provoked venous thromboembolism (VTE) and transient or persistent antiphospholipid antibodies (aPLs). We compared outcomes of patients aged <21 years with a first-episode acute provoked VTE and positive aPL at diagnosis, enrolled in the Multicenter Evaluation of the Duration of Therapy for Thrombosis in Children trial. aPLs were tested at enrollment and, when positive, repeated at 6 weeks after VTE diagnosis. Subsequent testing was performed at the discretion of the treating hematologist. Of 524 patients, 116 (22%) had positive aPLs at enrollment. At follow-up, 70 (60%) had transient (n = 66) or low-titer aPLs (n = 4), 11 (10%) had persistent aPLs meeting the criteria for antiphospholipid antibody syndrome (APS), and 35 (30%) had no repeat testing. Patients with APS were older (15.8 vs 9.9 years; P = .014) and had a statistically significant higher risk of symptomatic recurrent VTE (18% vs 1%; odds ratio [OR], 12.2; 95% confidence interval [CI], 1.4-108; P = .025) and a statistically nonsignificant but clinically meaningful difference in the risk of anticoagulant-related clinically relevant bleeding (9% vs 0%; OR, 20.1; 95% CI, 0.7-558; P = .077) compared with those in the transient or low-titer aPL group. In conclusion, aPLs are common in young patients with acute provoked VTE and are mostly transitory and clinically insignificant. Patients with APS and provoked VTE appear to have an increased risk of recurrent VTE compared with patients with transitory or low-titer aPLs. Future collaborative studies should investigate the optimal VTE management for children with provoked VTE who meet the criteria for APS. The trial was registered at www.ClinicalTrials.gov as #NCT00687882.

Outcomes and Predictors of Inpatient Mortality for Marantic Endocarditis Complicating Systemic Lupus Erythematosus: Contemporary Nationwide Study From the United States.

Systemic lupus erythematosus (SLE) patients are susceptible to marantic endocarditis (ME) due to a hypercoagulable state. The literature regarding the epidemiology and outcomes of ME in SLE patients is limited. All patients ≥18 years who had SLE with and without ME between 2007 and 2019 were identified from the National Inpatient Sample in the United States (US). Predictors of inpatient mortality for SLE patients with ME were analyzed. Between 2007 and 2019, there were 508,818 hospitalizations for SLE, of which 785 (0.2%) had ME. Of SLE patients with ME, 33 (4.2%) died while hospitalized over the study period. On multivariate analysis, female sex (adjusted odds ratio (aOR), 95% confidence intervals: 24.72 (3.21, 190.27)), age <34 years (aOR: 6.81 (1.80, 25.79)), anemia (aOR: 3.41 (1.12, 10.40)), antiphospholipid syndrome (aOR: 13.50 (3.83, 47.64)), stroke complicating ME (aOR: 9.64 (3.24, 28.71)), and acute kidney injury (aOR: 3.74 (1.06, 13.20)) were all associated with increased inpatient mortality among SLE patients with ME (P < .05 for all). Between 2007 to 2019, ME occurred in 0.2% of SLE hospitalizations, with a 4.2% average inpatient mortality over the study period. Female sex, antiphospholipid syndrome, and stroke were most strongly associated with increased inpatient mortality.

Antiphospholipid syndrome autoantibodies induction after treatment with anti-TNF alpha therapy in patients with IBD

IntroductionAnt-iTNF treatment has been broadly linked with autoantibodies and autoimmune disorders development. After the clinical observation of aPTT (activated partial thromboplastin clotting time) prolongation in our cohort of IBD patients treated with anti-TNF, we sought to determine the presence of antiphospolipid antibodies in our population, along with antiphospholipid syndrome (APS) occurrence. MethodsWe included in the study 289 patients treated with anti-TNFα antibodies. ResultsTwenty four of 289 patients presented a prolonged aPPT (8.3%) after starting anti-TNF treatment. We found antiphospholipid antibodies in 70.8% (17/24) of patients with aPTT prolongation. No major thrombotic events were reported although one patient met criteria for APS because of persistent antiphospolipid antibodies and two miscarriages. Another patient was diagnosed with lupus-like syndrome. ConclusionAnti-TNF treatment is associated with the induction of various antibodies, among them, antiphospholipid antibodies. However, a very low number of patients develop APS. Testing for antiphospholipid antibodies patients with prolonged aPPT could identify those at risk and lead to individualized treatment. Additional prospective studies are necessary to acquire more information.

Cryptogenic stroke and seronegative antiphospholipid syndrome: a case series of patients with positivity for "non-criteria" antiphospholipid antibodies.

Cerebrovascular events (CE) are one of the most common and severe events in antiphospholipid syndrome (APS), a condition characterized by thrombosis and circulating anti-phospholipid antibodies (aPL). Seronegative APS (SN-APS) refers to a group of patients with clinical features of APS but persistently negative tests for "criteria aPL": anti-cardiolipin antibodies (aCL) and anti-β2glycoprotein I antibodies detected by enzyme-linked immunosorbent assay (ELISA), and the lupus anticoagulant detected by clotting assays. We report a series of five cases of SN-APS in young or middle-aged patients who tested positive for "non-criteria" aPL. We retrospectively collected cases of SN-APS patients who experienced CE without an identified cause despite an extensive diagnostic work-up and tested negative for criteria aPL. All the patient sera were tested for aCL by immunostaining on thin-layer chromatography (TLC) and anti-vimentin/cardiolipin (aCL/Vim) by ELISA. We identified five cases of female patients aged 21 to 58 years, evaluated at the Rheumatology Unit and/or Stroke Unit/Emergency Department of the Sapienza University Hospital of Rome, "Policlinico Umberto I". All patients presented a clinical history suggestive of APS. All the patients tested positive for aCL by TLC-immunostaining, and one patient was positive for aCL/Vim. In young or middle-aged patients with cryptogenic CE and a clinical history suggestive of APS, the use of new diagnostic tools for identifying aPL, if validated in future studies, could represent an important step in the prompt diagnosis of APS.

Challenges in laboratory testing of patients suspected of antiphospholipid syndrome: practical implications for clinicians.

This paper focuses on the laboratory tests necessary for the diagnosis of antiphospholipid syndrome (APS). Diagnosis starts with the selection of patients suspicious of having APS. The timing related to the clinical event is important to avoid false classification of APS patients. For the interpretation of the test results of antiphospholipid antibodies (aPL) understanding of all pitfalls and interferences is necessary. Lupus anticoagulant (LA) measurement remains a complex procedure with many pitfalls and interferences. The effect of anticoagulant therapy, the main confounder of LA measurement, can be overcome by removal agents for direct oral anticoagulants (DOAC) or by considering assays as Taipan snake venom time / Ecarin clotting time not affected by antivitamin K therapy and anti-Xa DOAC. However, both procedures have limitations. Solid-phase assays for anticardiolipin antibodies (aCL) and anti-β2-glycoprotein 1 antibodies (aβ2GPI) show inter-assay differences. Diagnosis is based on the measurement of three groups of aPL: LA, aCL and aβ2GPI, of IgG and IgM isotype. This allows to make antibody profiles that helps in identifying patients at risk. Other aPL, such as antibodies against the domain I of β2GPI and anti-phosphatidylserine-prothrombin antibodies may be useful in risk stratification of APS patients and in some specific situations of patients with incomplete antibody profile, but are not needed for diagnosis. Laboratory diagnosis of APS remains challenging. To increase the diagnostic efficacy and reliability, an integrated interpretation of all results and an interpretative comment should be provided on the laboratory report. Therefore, a close interaction between clinical pathologists and clinicians is mandatory.

Challenging cases in rheumatic disease pregnancy: management perspectives from reproductive rheumatologists

Pregnant women with rheumatic and musculoskeletal diseases (RMDs) have a higher risk of adverse pregnancy and perinatal outcomes compared to those without RMDs. Although evidence-based guidelines have been developed for the reproductive health care and management of these individuals, multiple areas of uncertainty exist around the diagnosis and treatment of pregnant patients with confirmed or suspected RMDs. We present a series of outpatient cases that address areas of uncertainty in the field of reproductive rheumatology. Expert opinions were elicited from rheumatologists who have expertise in the reproductive health of individuals with RMDs to build new understanding around diagnosis or treatment approaches. The cases focused on the interpretation of antiphospholipid antibodies in various clinical scenarios, diagnosis and management of nephrotic-range proteinuria during pregnancy, and the use of tumor necrosis factor inhibitors during pregnancy. Our objective was not to replace existing guidelines and classification criteria but rather to provide a range of expert opinions that rheumatologists might consider when tailoring treatment and care for patients, particularly in challenging situations with limited data.

Hypogammaglobulinemia in a child with atypical hemolytic-uremic syndrome

We present a unique clinical case of an atypical hemolytic-uremic syndrome in a child. The mutation in exon 6 of the CD46 gene (chr1:207940532G&gt;C) leads to a homozygous or hemizygous missense substitution. An 8-year-old girl was urgently hospitalized with symptoms of hemorrhagic syndrome and acute kidney injury. The child from the second pregnancy with an aggravated obstetric anamnesis, the first operative labor at the 38th week, who has an aggravated genealogical anamnesis. Initially, the disease developed in the guise of gastroenterological pathology: the girl had dyspeptic disorders, most likely associated with pathology of carbohydrate metabolism, also frequent infectious diseases and a lag in physical development. From the age of 4 years, the girl suffered from persistent hypoalbuminemia, hypoproteinemia and hypogammaglobulinemia, requiring replacement therapy with intravenous immunoglobulins. She was repeatedly examined in gastroenterological departments in Yekaterinburg and Moscow in 2021-2023, but no data concerning protein-losing enteropathies or primary immunodeficiency was obtained. Also, the whole-exome sequencing with result validation hasn’t confirmed an inherited etiology of the presumed congenital immune error. However, a CD46 gene mutation, associated with the development of hemolytic-uremic syndrome in some publications, was identified in the study. The signs of thrombotic microangiopathy were preceded by fever of unspecified etiology: microangiopathic hemolysis, thrombocytopenia, hyperazotemia, C3 consumption, proteinuria, and macrohematuria; hypercholesterolemia, protein metabolism disorder, increased transaminases, ferritin were also noted. According to the ultrasound of the kidneys there were diffuse changes in the parenchyma, decreased velocity indices of blood flow in both renal arteries at all levels. Differential diagnosis was carried out with thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, antinuclear form of atypical hemolytic-uremic syndrome, viral and bacterial infections, systemic pathology, antiphospholipid syndrome, and hemoblastosis. The girl didn’t need a renal replacement therapy. When complement-blocking therapy with eculizumab was initiated on vital indications, the signs of the disease were gradually eliminated. The prolonged absence of nephropathy in the child may indicate the diversity of the CD46 gene’s functions and different phenotypic manifestation of its mutations. Analysis of literature sources and detection of CD46 “environment” genes (CYBA, LYST, ARPCIB) by full-exome sequencing suggest ambiguity and polymorphism of phenotypic manifestations of complement-mediated mutation.

Enfermedad microvascular coronaria en gestante con antecedente de síndrome antifosfolípidos

Objective: to report the case of a pregnant woman with antiphospholipid syndrome history, in whom coronary microvascular disease was documented. Antenatal medical treatment improved prognosis and maternal and perinatal outcomes. Case: multigravida woman, 29.6 weeks pregnant, diagnosed with acute coronary syndrome, referred from a first level hospital. Diagnostic workup revealed microvascular disease. After receiving adequate management, she was discharged from hospital and included in the high-risk pregnancy program. Results: the diagnosis was made based on echocardiography, electrocardiography, troponin levels and cardiac catheterization. Anti-ischemic therapy was indicated considering the risk-benefit trade-off; management with aspirin was continued and the baby was born healthy. Conclusions: coronary microvascular disease should be considered, as a differential diagnosis in a pregnant woman with chest pain and history of antiphospholipid syndrome. Patients benefit from receiving antiplatelet and anticoagulant therapy soon after the diagnosis is made. Studies are required to evaluate the safest and most effective management of this condition.

Antiphospholipid antibodies in patients with systemic lupus erythematosus – diagnostic significance and clinical implications. Own observations

Antiphospholipid antibodies in patients with systemic lupus erythematosus – diagnostic significance and clinical implications. Own observations

Placental lesions in patients with antiphospholipid antibody syndrome: experience of a single tertiary-care Italian reference center

IntroductionAbnormal placentation contributes to obstetric morbidity in antiphospholipid antibodies syndrome (APS). The placenta is the main target of antiphospholipid antibodies (aPL) in obstetric APS and is the site of dysfunctional inflammatory responses and thrombosis. Standard treatment for APS during pregnancy includes low-dose aspirin (LDA) plus low molecular weight heparin (LMWH) and, in refractory cases, hydroxychloroquine (HCQ). Recently, a systematic review of the literature identified five main pathological placental lesions in APS patients: placental infarction, decidual vasculopathy, decidual inflammation, increase of syncytial knots due to syncytiotrophoblast death, and decrease in vasculosyncytial membranes. The aims of this study were to investigate whether placental lesions associate with obstetrical outcomes in a cohort of APS patients.Methods130 pregnant APS patients evaluated between 2009 and 2023 at the High-Risk Obstetrics Outpatient Clinic of San Raffaele Hospital, Milan, were enrolled. Placental samples from 25 spontaneously conceived pregnancies in APS patients were collected from January 2017 to May 2023 and analyzed.ResultsAll (n = 130) patients were on LDA and 110/130 (85%) on both LDA and LMWH. Twenty-six patients (20%) also received HCQ. In these patients, signs of placental inflammation (preterm birth and preterm premature rupture of membranes) were less frequently observed. Of the 25 placental samples analyzed, 19 (76%) patients had primary APS, while 6 patients had APS secondary to SLE. All patients were treated with LDA and LMWH. In patients with concomitant systemic lupus erythematosus (SLE) or in refractory APS, HCQ was added. Histological analysis of placental tissue revealed increased syncytial knots in 17/25 (68%) placentas, decreased vasculosyncytial membranes in 11/25 (44%), infarction in 8/25 (32%), presence of macrophages and decidual inflammation in 2/25 (8%), and atherosis or reduction of spiral artery remodeling in 3/25 (12%). We also observed at least two coexisting placental lesions in 12/25 (48%) placentas. In the placenta of patients treated with HCQ we did not observe any decidual inflammation at histology.ConclusionPlacental anomalies have occurred in patients with APS despite close and optimal obstetric monitoring. It is thus tempting to speculate that HCQ may have beneficial effects on pregnancy by decreasing the risk of deciduitis in patients with APS.

Catastrophic Antiphospholipid Syndrome: A Review of Current Evidence and Future Management Practices.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by blood clots and pregnancy complications due to antiphospholipid antibodies. Catastrophic APS (CAPS), a severe variant, leads to multiorgan failure and is often fatal. Pathogenesis involves antiphospholipid antibodies, particularly anti-beta-2-glycoprotein I (aβ2GPI), which trigger endothelial cell (EC) activation, cytokine release, and a prothrombotic state. Infections, surgeries, and other triggers can precipitate CAPS, leading to widespread microthromboses and systemic inflammatory responses. CAPS predominantly affects younger patients and those with systemic lupus erythematosus (SLE), with a high mortality rate, though recent treatment advances have improved survival. Diagnosing CAPS involves identifying clinical manifestations, including rapid organ involvement and small vessel occlusions, confirmed by histopathology and high antiphospholipid antibody levels. The CAPS registry data indicate that commonly affected organs include kidneys, lungs, central nervous system, and the heart, with a high prevalence of lupus anticoagulant and anticardiolipin antibodies (aCL). Current management strategies focus on therapeutic anticoagulation, immunosuppressive therapies like corticosteroids, and adjunct treatments such as plasmapheresis and intravenous immunoglobulin (IVIG). Early use of glucocorticoids and combination therapy has significantly improved outcomes. In life-threatening cases, especially with microangiopathy, experts recommend performing plasma exchange (PE). Patients with associated autoimmune conditions or refractory cases may receive cyclophosphamide (CY) and rituximab while considering PE for treatment. Maintenance of anticoagulation with an appropriate international normalized ratio (INR) is crucial to prevent recurrence.This article reviews the pathogenesis and epidemiology of CAPS. It also examines the current management strategies, and discusses the challenges and controversies associated with these strategies. It hereafter offers recommendations for future management and outlines directions for further research.

Recurrent Pregnancy Loss: Immunological aetiologies and associations with mental health

Recurrent pregnancy loss (RPL) is an obstetric condition estimated to affect 2–4% of childbearing individuals globally. Due to its varied nature, medical societies globally differ in their diagnostic criteria. Its aetiologies are numerous, ranging from anatomic abnormalities to endocrine and immunological factors. Autoimmune factors can attribute to approximately 20% of cases and include dysregulation of immune cells, cytokine production and antiphospholipid syndrome. Treatment pathways vary by aetiology; however, many cases remain unexplained, adding an additional level of complexity to this condition. Due to its recurrent nature, this type of pregnancy loss has profound impacts on mental health during subsequent pregnancies. While some aspects of RPL have been widely investigated, there continues to be a gap in research, such as its impacts on non-birthing parents and specific sociodemographic groups.

Awareness and Frequency of Encounter With Subjects With Antiphospholipid Syndrome by Medical Practitioners in Tertiary and Some Other Health Institutions in Southeast Nigeria

Abstract Background: Antiphospholipid syndrome (APS) is an autoimmune multisystem disorder. There has been a limited number of reported cases from Nigeria. Objectives: To determine the awareness and frequency of encounters with APS cases by medical practitioners in health institutions in South East Nigeria. Materials and Methods: It was a descriptive cross-sectional study. All medical doctors met in the clinics who were willing to participate in the study were recruited during the period of the study. Statistical Package for Social Sciences was used for data entry, validation, and analysis. Results: A total of 581 study questionnaires were distributed to medical doctors met at the clinics and clinical meetings of five hospitals in Southeast Nigeria however, 581 were approximately filled and retrieved, giving an response rate of 94.84%. Males were 383 (69.5%) and females were 168 (30.5%). A total of 445 (80.8%) were unaware of the autoimmune multisystemic nature of APS. Of the 551 respondents, 348 (63.2%) were aware that Rheumatologist is the primary care physician for APS, 290 (52.6%) reported rarity of APS, and 366 (66.4%) had up to 50% overall knowledge of APS. Respondents’ encounters with unexplained thrombotic events and unexplained stroke in the young were limited. A total of 62 (11.3%) were aware of the international classification criteria for APS. Conclusion: The authors conclude that APS awareness among medical practitioners in South East Nigeria is suboptimal.

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

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. 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). Forty-five patients (73% females, median age 49years) 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). 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.

Clinical Features and Survival Analysis of Lupus Nephritis among Patients with Systemic Lupus Erythematosus: A Three-Decade-Long Retrospective Cohort Study.

Background/Objectives: Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). The aim of our retrospective cohort study was to compare the clinical characteristics, therapy, survival, causes of death, and prognostic factors of LN and non-LN lupus patients. Moreover, we compared a wide spectrum of clinical data of LN patients diagnosed before and since 2005 to determine any changes in disease course and outcomes. Methods: We assessed the clinical and laboratory data of 384 SLE patients, out of whom, 127 patients were diagnosed with LN between 1990 and 2020. Results: Based on our observations, discoid LE, subacute cutaneous LE, antiphospholipid syndrome, Sjögren's syndrome, and rheumatoid arthritis were more common in non-LN patients, while anemia and anti-RNP positivity were more frequent in LN patients. Development of LN did not affect survival rates; male sex and presence of APS were negative prognostic parameters in the non-LN group while achieving remission was a positive prognostic factor in both groups. Death caused by sepsis was more prevalent in the LN group. Serositis and neurological manifestations occurred less frequently in LN patients diagnosed after 2005. The use of mycophenolate mofetil became more common, and the cumulative corticosteroid dose decreased. The SLICC Damage Index score also decreased. Conclusions: Our study demonstrated that the disease course has changed in recent years, and the main therapeutic goal in both SLE and lupus nephritis should be to achieve remission because this significantly improves long-term prognosis and patient survival.