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COVID-19 may induce a state of hypercoagulability, particularly in critically ill patients, for reasons that remain unknown. Numerous studies have identified the presence of antiphospholipid antibodies in patients with COVID-19; however, the definitive diagnosis of antiphospholipid syndrome continues to pose challenges. Here, we present the case of a patient infected with SARS-CoV-2 who developed life-threatening severe thrombocytopenia, profound anaemia, acute pulmonary hypertension, right ventricular failure, and renal insufficiency. Laboratory investigations revealed significantly elevated levels of antiphospholipid antibodies. We conducted a one-year follow-up study with blood sampling performed every 12 weeks. The patient exhibited persistent high titres of antiphospholipid antibodies and ongoing renal dysfunction necessitating daily oral warfarin antithrombotic therapy. Antiphospholipid syndrome is a complex clinical condition that poses challenges for clinicians, particularly in critically ill patients, and is often associated with delayed and inaccurate diagnosis and treatment. Therefore, we extensively reviewed the literature and international guidelines to conduct a comprehensive analysis of the aetiology, pathogenesis, and treatment strategies of APS. We hope this work will provide a valuable reference for health care professionals. [ABSTRACT FROM AUTHOR]

Lupus anticoagulant (LA) is a well-established risk factor for the clinical manifestations of antiphospholipid syndrome (APS). Accurate LA detection is an essential prerequisite for optimal diagnosis and management of patients with APS or aPL carriers. Variability remains a challenge in LA testing, with reliable detection influenced by multiple factors, including pre-analytical conditions, anticoagulation treatment, choice of tests and procedures performed, as well as interpretation of results, that can lead to false-positives or negatives. A standardised approach to LA testing, following current guidance, based on published data and international consensus, and with attention to detail, is required to underpin accurate detection of LA. Future work should focus on better characterisation of the nature of LA, which may ultimately lead to improved diagnosis and management of patients with APS and aPL carriers. This article reviews current practice and challenges, providing an overview on detection of LA. [ABSTRACT FROM AUTHOR]

Catastrophic antiphospholipid syndrome (CAPS) is a severe condition with high mortality. Since its description in 1992, an important effort has been made to improve and disseminate knowledge on CAPS. Most of our current knowledge comes from the studies performed using the CAPS Registry, a database created in 2000 to gather as many cases as possible in order to better define this disease. It has demonstrated that this condition has multiple faces and is often triggered by a precipitating factor that leads to a thrombotic microangiopathy and cytokine storm involving almost any organ of the body. Analysis of the CAPS Registry has also shown that patients receiving anticoagulation, glucocorticoids and plasma exchange and/or IVIG have a better prognosis. However, there are still many unresolved questions. In this review we summarize what is known and what is still a matter of research in this condition. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder resulting in thrombosis, microvascular disease, morbidity in pregnancy, and/or non-thrombotic manifestations. The recently introduced 2023 American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) APS classification criteria, with significantly higher specificity compared to the revised Sapporo criteria, now reflect the current thinking about APS and provide a new foundation for future APS research. The purpose of this short commentary is to discuss the appropriate circumstances under which the 2023 ACR/EULAR classification criteria could be used and to demonstrate how the new criteria can be applied to simple case scenarios. [ABSTRACT FROM AUTHOR]

Introduction: Triple antibody positive antiphospholipid syndrome during pregnancy carries a poor prognosis. The placental vasculature is particularly vulnerable to these antibodies resulting in a marked increased risk of fetal growth restriction, placental infarction, abruption, stillbirth, and preterm severe preeclampsia. Case Presentation: We report a case of a primigravida with triple antibody positive antiphospholipid syndrome that demonstrated placental insufficiency and fetal compromise at a previable gestation. The patient underwent plasma exchange every 48 h for 11 weeks resulting in delivery of a viable infant. Placental blood flow was improved after complete absence of end-diastolic flow in the fetal umbilical artery. Conclusion: Scheduled plasmapheresis every 48 h can be considered in select cases of antiphospholipid antibody syndrome. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate clinical presentations, antiphospholipid antibody patterns and their levels, therapeutic regimens, and outcomes in patients with antiphospholipid syndrome (APS) admitted to a tertiary care hospital of a South Asian country. Patients and methods: Between January 2009 and December 2019, a total of 216 patients with APS (8 males, 208 females; median age: 35.7±6.9 years; range, 20 to 76 years) who either fulfilled the modified Sydney criteria or those who satisfied only clinical criteria along with positive antiphospholipid antibody on at least one occasion (probable APS) were retrospectively analyzed. Results: The majority of the patients (n=183, 84.7%) had obstetric complications, followed by venous thrombosis in 23 (10.8%) patients. Recurrent early abortions in 126 (58.6%) and deep venous thrombosis in 16 (7.4%) patients were the most prevalent obstetrical and venous events, respectively, whereas limb gangrene in seven (3.3%) and ischemic stroke in seven (3.3%) were the most common arterial events. A total of 190 (88%) patients had primary APS, while 26 (12%) had secondary APS. Systemic lupus erythematosus was the frequent association with secondary APS found in 19 (73%) patients. Immunoglobulin M (IgM) anticardiolipin antibody was present in 173 (65.0%) patients, being the most commonly reported antibody. Probable catastrophic APS was found in four (1.9%) patients. Majority of the patients (n=190, 87.9%) were treated with a combination of acetylsalicylic acid and low-molecular-weight heparin. Single mortality was observed in our study population due to complications related to catastrophic APS. Conclusion: Antiphospholipid syndrome has a wide range of thrombotic and obstetrical manifestations with important variations in different regions of the world. There is a significant morbidity and mortality related to APS, despite treatment with anticoagulation and; therefore, describing prognostic markers and optimal therapeutic interventions is pivotal to prevent complications. [ABSTRACT FROM AUTHOR]

Catastrophic antiphospholipid syndrome (CAPS) is a rare life threatening presentation of antiphospholipid syndrome. Surgery has been proposed as one of the triggering factors for this life threatening entity. There are no detailed published reports in the current literature describing CAPS as a complication after surgery. We report a case of a 21 year old that developed CAPS postoperatively and discuss the multidisciplinary approach for diagnosis and management. [ABSTRACT FROM AUTHOR]

Objective We aimed to analyse the prevalence of non-criteria anti-phospholipid (aPL) antibodies and their role in the diagnosis, treatment and prognosis in a cohort of patients with clinical features consistent with a diagnosis of antiphospholipid syndrome (APS), but persistently negative for criteria aPL – anti-cardiolipin antibodies (aCL), anti-β2-glycoprotein I antibodies (aβ2-GPI) and lupus anticoagulant (LA) – named seronegative APS (SN-APS). Methods Sera from SN-APS patients were tested for aCL by TLC-immunostaining, anti-vimentin/cardiolipin (aVim/CL) and anti-phosphatidylserine/prothrombin (anti-PS/PT) by ELISA. Control groups of our study were APS patients and healthy controls. Results We enrolled 114 consecutive SN-APS patients, 69 (60.5%) resulted positive for at least one non-criteria test in two occasions 12 weeks apart. Among the persistently positive patients to these tests, 97% resulted positive for aCL by TLC-immunostaining, 52.3% for aVim/CL and 17.4% for aPS/PT. SN-APS patients with double positivity (aCL by TLC-immunostaining and aVim/CL) showed a likelihood positive ratio of 8 to present mixed thrombotic and obstetrical features. Among SN-APS patients tested positive, after the therapeutic changes, three cases of recurrent thrombosis were observed [median follow-up 41 months (IQR 39.5)]. Twenty pregnancies were recorded in 17 SN-APS patients after the detection of unconventional aPL and 12 of them (60%) experienced a good outcome under conventional treatment for APS. Conclusions This is the largest monocentric study demonstrating that aCL tested by TLC-immunostaining and aVim/CL can detect aPL positivity in SN-APS. It may encourage clinicians to monitor and provide adequate targeted therapy, which improve SN-APS prognosis. [ABSTRACT FROM AUTHOR]

Background: Antiphospholipid Syndrome (APS) is a multisystemic autoimmune disease characterized by arterial and venous thrombosis and / or obstetric morbidity in the presence of at least one circulating anti-phospholipid antibody. The spectrum of vascular events varies from deep venous thrombosis to catastrophic APS, a rare form characterized by acute multiorgan thrombosis and high mortality. Case report: We present the case of a 32-week pregnant woman arriving in the hospital emergency room with bilateral acute lower limb ischemia. In the obstetric evaluation, fetal death was declared. Computerized Tomography angiography showed pulmonary embolism of both pulmonary arteries, areas of splenic and right renal infarction and multiple arterial and venous thrombosis. The patient underwent urgent caesarean section and axillary-bifemoral bypass. No events registered. In the postoperative period, in an intensive care unit, treatment with rituximab and plasmapheresis were added to anticoagulant therapy. The laboratorial investigation was negative for thrombophilia and autoimmune diseases. Conclusion: Catastrophic APS develops quickly, with multiorgan involvement and high mortality rate. The presented case poses a multidisciplinary challenge, with the surgical approach of extra-anatomical revascularization being less invasive and guaranteeing immediate perfusion of the lower limbs. Although the serological tests were negative for anti-phospholipid antibodies, this case hardly fits into another diagnosis. Therefore, it was treated as a catastrophic APS, having shown a favorable evolution. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 50-year-old man with antiphospholipid syndrome (APS) presents to your office for the first time with a 3-month history of worsening dyspnea, dry cough, and early morning blood-tinged sputum. Topics include the APS diagnosis was based on an unprovoked left leg deep vein thrombosis, and the physical examination is normal except for livedo racemosa around his knees.

The article focuses on evaluating the frequency and thoroughness of anti-phospholipid antibody (aPL) screening in systemic lupus erythematosus (SLE) patients at the Counties Manukau District Health Board. It highlights issues in screening completeness, patient compliance, and the need for better education on management guidelines among healthcare providers.

What is known and objective: Oxcarbazepine (OXC) is an antiepileptic drug. Patients suffering from chronic kidney disease with an estimated glomerular filtration rate below 30 ml/min/1.73 m2 require dose adjustments for OXC. Case summary: A 31‐year‐old man was admitted with a history of diplopia, ataxia and dizziness attacks that had disappeared after a regular haemodialysis sessions for three months. Medical history was remarkable for primary antiphospholipid syndrome (APS). However, no signs of new‐onset APS‐related neurological involvement were present. Then, it was revealed that the patient had been using 2400 mg/day of OXC for four months, despite the prescription of half of this dose. Serum OXC level was 50 mcg/ml (reference: 3–35 mcg/ml) before a regular haemodialysis session. All symptoms disappeared in a few days after reducing to 1200 mg/day and never recurred. What is new and conclusion: We reported a chronic OXC intoxication in a patient on maintenance haemodialysis. To the best of our knowledge, it is the first chronic OXC intoxication case in the literature. It could be related to episodic removal of OXC and its metabolites via haemodialysis. Consequently, dose modification of drugs is a pivotal point in haemodialysis patients. Chronic drug intoxications must be kept in mind in haemodialysis patients with unexplained symptoms. [ABSTRACT FROM AUTHOR]

Objectives The aims were to gain insight into the care provided to patients with APS in The Netherlands and to identify areas for improvement from the perspective of both patients and medical specialists. Methods APS care was evaluated using qualitative and quantitative methods. Perspectives on APS care were explored using semi-structured interviews with medical specialists, patient focus groups and a cross-sectional, online patient survey. In order to assess current practice, medical records were reviewed retrospectively to collect data on clinical and laboratory manifestations and pharmacological treatment in six Dutch hospitals. Results Fourteen medical specialists were interviewed, 14 patients participated in the focus groups and 79 patients completed the survey. Medical records of 237 patients were reviewed. Medical record review showed that only one-third of patients were diagnosed with APS within 3 months after entering specialist care. The diagnostic approach and management varied between centres and specialists. Almost 10% of all patients and 7% of triple-positive patients with thrombotic APS were not receiving any anticoagulant treatment at the time of medical record review. Correspondingly, poor recognition and fragmentation of care were reported as the main problems by medical specialists. Additionally, patients reported the lack of accessible, reliable patient education, psychosocial support and trust in physicians as important points for improvement. Conclusion Delayed diagnosis, variability in management strategies and fragmentation of care were important limitations of APS care identified in this study. A remarkable 10% of patients did not receive any anticoagulant treatment. [ABSTRACT FROM AUTHOR]

Background: The antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by thrombotic events that can require ICU admission because of organ dysfunction related to macrovascular and/or microvascular thrombosis. Critically ill patients with thrombosis and APS were studied to gain insight into their prognoses and in-hospital mortality-associated factors.Methods: This French national, multicenter, retrospective study included all patients with APS and any new thrombotic manifestations admitted to 24 ICUs (January 2000-September 2018).Results: During the study period, 134 patients (male/female ratio, 0.4) with 152 APS episodes were admitted to the ICU (mean age at admission, 46.0 ± 15.1 years). In-hospital mortality of their 134 last episodes was 35 of 134 (26.1%). The Cox multivariable model retained certain factors (hazard ratio [95% CI]: age ≥ 40 years, 11.4 [3.1-41.5], P < .0001; mechanical ventilation, 11.0 [3.3-37], P < .0001; renal replacement therapy, 2.9 [1.3-6.3], P = .007; and in-ICU anticoagulation, 0.1 [0.03-0.3], P < .0001) as independently associated with in-hospital mortality. For the subgroup of definite/probable catastrophic APS, the Cox bivariable model (including the Simplified Acute Physiology Score II score) retained double therapy (corticosteroids + anticoagulant, 0.2 [0.07-0.6]; P = .005) but not triple therapy (corticosteroids + anticoagulant + IV immunoglobulins or plasmapheresis: hazard ratio, 0.3 [0.1-1.1]; P = .07) as independently associated with in-hospital mortality.Conclusions: In-ICU anticoagulation was the only APS-specific treatment independently associated with survival for all patients. Double therapy was independently associated with better survival of patients with definite/probable catastrophic APS. In these patients, further studies are needed to determine the role of triple therapy. [ABSTRACT FROM AUTHOR]

Introduction: To assess the clinical performance and correlations of automated chemiluminescence assay (CIA) and enzyme‐linked immunosorbent assay (ELISA) for detecting antiphospholipid (aPL) antibodies in the diagnosis of antiphospholipid syndrome (APS). Methods: The study recruited 505 subjects, including 192 with APS, 193 with connective tissue diseases other than APS, and 120 healthy donors. We measured anticardiolipin (aCL) and anti‐β2‐glycoprotein I (anti‐β2GPI) antibodies IgG, IgM, and IgA in all the samples using both CIA and ELISA. Results: Total agreement between the two methods ranged from 83.50% for anti‐β2GPI IgG antibodies to 92.76% for anti‐β2GPI IgM antibodies in all the groups. Anti‐β2GPI and aCL IgG assays showed the highest Spearman's rho coefficients (anti‐β2GPI IgG = 0.742, aCL IgG = 0.715). Anti‐β2GPI IgG CIA showed the highest sensitivity for diagnosis of APS at 80.21%, which was significantly higher than the sensitivity of anti‐β2GPI IgG ELISA (52.08%). For diagnosis of APS, anti‐β2GPI IgG CIA had the best discrimination power with the area under the curves (AUC) of 0.922, followed by aCL IgG CIA (AUC of 0.905). While the CIA AUC was slightly higher in all cases, the difference was not statistically significant. Conclusion: CIA measurements had a good agreement and correlation with comparative ELISA assays. The CIA anti‐β2GPI IgG however was significantly more sensitive for APS diagnosis. The two assay methodologies showed comparable predictive powers and support the value of the CIA method for improved diagnosis and management of patients with APS. [ABSTRACT FROM AUTHOR]

The current COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to distinct diagnostic and management challenges for front-line healthcare workers. The risk of excessive coagulation activation leading to a cascade of thrombotic events in critically ill patients with SARS-CoV-2 is now well reported. We discuss a recent case of COVID-19 with concurrent acute pulmonary embolism and a positive cardiolipin antibody (IgM). The presence of antiphospholipid antibodies is key to diagnosing antiphospholipid syndrome (APS). However, their presence can be transient or persistent after viral infections. Serial inflammatory markers in conjunction with anti-phospholipid antibody testing is critical for the diagnosis of APS in this emerging patient population. Our case report reviews details suggestive of APS in the setting of SARS-CoV-2 and aims to provide clinical diagnostic clues that could help warrant further workup and assist with management strategies. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombosis and/or pregnancy morbidity. The incidence is around five new cases/100,000 persons per year and the prevalence is around 40–50 cases/100,000. The prevalence is higher (about 30%) among patients with systemic lupus erythematosus. APS is associated with circulating antiphospholipid antibodies (aPLs), a heterogeneous group of autoantibodies directed against negatively charged molecules and a combination of protein-complexed phospholipids. The predominant protein antigen in this disorder is beta 2-glycoprotein I (β2GPI). Despite the discovery of "new" antigenic targets and development of "new" methodological approaches, the laboratory diagnosis of APS is still an evolving field and studies to identify further antigenic target(s) as potential diagnostic markers and risk predictors are in progress. In particular, recent studies were aimed at analyzing the pathogenic role of post-translational modifications (PTMs) of proteins induced by inflammation and/or oxidative stress as modulators of protein structure and function and possibly as a source of antigenic epitopes. The present review is focused on PTMs of self-proteins responsible for autoimmune reactions in patients with APS. At present, the known PTMs in APS involve β2GPI. In particular, the PTM of β2GPI via thiol-exchange reactions is a highly specific phenomenon that makes the protein more antigenic. Other PTMs, including sialylation and acetylation, may affect β2GPI antigenicity. Moreover, the addition or loss of carbohydrate chains affects β2GPI immunoreactivity since carbohydrates are determining factors for β2GPI conformation. In addition to β2GPI, PTMs of other self proteins such as vimentin and annexins may play a role in the immune response during APS. The study of PTMs is useful to clarify the role of modified proteins in the pathogenesis of APS as well as to design more efficient diagnostic/prognostic tools and more targeted therapeutic approaches. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by recurrent thrombosis, other associated autoimmune disease, and/or obstetrical morbidity along with persistent production of antiphospholipid antibodies. Because of the nature of this systemic disease, most patients are medicated with antithrombotic agents and abundant glucocorticoids. This study reports a cohort of 16 patients with APS, who underwent oral surgery between 2010 and 2017 at the Nagasaki University Hospital. Because oral antithrombotic therapy was continued in the perioperative period, all wounds were strictly closed by suturing to prevent postoperative bleeding. Perioperative laboratory dates and medications were assessed. All patients achieved local postoperative hemostasis and did not exhibit systemic complications. Moreover, there were no postoperative systemic and/or local infections. Oral surgeons should suture oral wounds and ensure local hemostasis to prevent postoperative bleeding. Because patients with APS are likely to develop thrombosis despite continued administration of antithrombotic medications, strict perioperative examination of blood coagulation is needed. Furthermore, it is important to consider the damage and stress caused due to oral surgery. Moreover, when necessary, glucocorticoid therapy should be carefully administered, in accordance with the degree of invasion and judgment of the attending physician. [ABSTRACT FROM AUTHOR]

Objectives: We discuss two patients with antiphospholipid syndrome (APS) who presented with critical ischemia of both lower extremities due to arterial microthrombi. They received multimodality therapy emergently: anticoagulation, immunosuppression, and therapeutic plasma exchange (TPE). Then they were maintained on anticoagulation with fondaparinux and immunosuppression with mycophenolate mofetil (MMF), and were followed for 4 years. Methods: Two patients with APS with ischemia and necrosis of their distal lower extremities were treated emergently with anticoagulation (intravenous heparin), immunosuppression (prednisone), and TPE. They were maintained on anticoagulation with fondaparinux and immunosuppression with MMF. Results: Neither patient had recurrent microthrombotic disease during a 4-year follow-up. Conclusions: As described in our small cohort, patients with APS who suffer from microthrombotic arterial disease may benefit from maintenance therapy of anticoagulation with fondaparinux and immunosuppression with MMF, an approach which may be worthy of further trial. Fondaparinux does not require attention to diet, monitoring, and cumbersome bridging that is typical of warfarin therapy. MMF provides immunosuppression while sparing the side effects of steroid treatment. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APLS) is characterised by venous or arterial thrombosis and/or adverse pregnancy outcome in the presence of persistent laboratory evidence of antiphospholipid antibodies. Catastrophic Antiphospholipid Syndrome (CAPS) is a severe and rare form of antiphospholipid syndrome characterised by multiple site thrombosis involving small, medium and large blood vessels occurring over a short period of time (usually 1 week) causing multiorgan failure. We present an unusual case of left upper limb acute arterial thrombosis with purpura fulminans like skin lesions precipitated by swine flu (H1N1) infection with adult respiratory distress syndrome subsequently developing acute renal failure, retinal infarcts, multiple acute cerebral infarcts, cardiac valvular vegetations and hemolytic anemia with recurrent bleeding episodes. A positive lupus anticoagulant confirmed the diagnosis of CAPS. In spite of early initiation of triple therapy (anticoagulation, high dose steroids, plasmapheresis) our patient did not survive. This rare case of probable CAPS is presented with an aim to study the clinical manifestations, laboratory findings, efficacy of therapy and prognosis in the medical ICU. [ABSTRACT FROM AUTHOR]

Abstract The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%–21% at 5 years in thrombotic APS and 20–28% in obstetrical APS [2, 3]. Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4–16]. Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency. Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial. This trial consists in two parts: a retrospective and a prospective study. The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS. [ABSTRACT FROM AUTHOR]

To describe a novel technique utilizing an amniotic membrane graft (AMT) to create the mucocutaneous portion of the lower eyelid margin in a modified Hughes eyelid reconstruction for secondary revision or prevention of a hyperemic, hypertrophic conjunctival margin with excessive discharge. This was a retrospective, non-comparative interventional study. Thirty consecutive patients who underwent a modified Hughes reconstruction were included. The first step of the reconstruction was performed in a standard fashion using a tarsoconjunctival flap from the ipsilateral upper eyelid. The second stage was accomplished by the division of the tarsoconjunctival flap. The modification of the procedure included the addition of AMT (Ambio 5®, IOP Ophthalmics, CA) to the new mucocutaneous junction. Main outcome measures included the post Mohs surgery defect size, post-reconstruction complications. One patient received AMT for a revision of a hyperemic lid margin following reconstruction, while 29 subsequent patients received AMT as a primary procedure. The mean size of the post-Mohs defect was 23.75 ± 6.6 mm2 horizontally and 9.1 ± 5.4 mm2 vertically, involving 79.53 ± 16.8% of the lower eyelid. There was no evidence of hyperemic or hypertrophic margin at a mean follow-up of 4.41 ± 2.91 months. The addition of an AMT for the revision, or as a primary procedure for prevention of a hyperemic, hypertrophic eyelid margin with excess mucus production in the post-Hughes lower eyelid reconstruction has favorable outcomes in this preliminary study, however warrants further investigation with larger number of patients and longer follow-up. [ABSTRACT FROM AUTHOR]

Rivaroxaban is an effective and safe alternative to warfarin in patients with atrial fibrillation and venous thromboembolism. We tested the efficacy and safety of rivaroxaban compared with warfarin in high-risk patients with thrombotic antiphospholipid syndrome. This is a randomized open-label multicenter noninferiority study with blinded end point adjudication. Rivaroxaban, 20 mg once daily (15 mg once daily based on kidney function) was compared with warfarin (international normalized ratio target 2.5) for the prevention of thromboembolic events, major bleeding, and vascular death in patients with antiphospholipid syndrome. Only high-risk patients triple positive for lupus anticoagulant, anticardiolipin, and anti-b2-glycoprotein I antibodies of the same isotype (triple positivity) were included in the study. The trial was terminated prematurely after the enrollment of 120 patients (59 randomized to rivaroxaban and 61 to warfarin) because of an excess of events among patients in the rivaroxaban arm. Mean follow-up was 569 days. There were 11 (19%) events in the rivaroxaban group, and 2 (3%) events in the warfarin group. Thromboembolic events occurred in 7 (12%) patients randomized to rivaroxaban (4 ischemic stroke and 3 myocardial infarction), whereas no event was recorded in those randomized to warfarin. Major bleeding occurred in 6 patients: 4 (7%) in the rivaroxaban group and 2 (3%) in the warfarin group. No death was reported. The use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with an increased rate of events compared with warfarin, thus showing no benefit and excess risk. This trial was registered at www.clinicaltrials.gov as #NCT02157272. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the clinical significance of laboratory findings in patients with catastrophic antiphospholipid syndrome (CAPS) and to report the effects of a well-defined treatment protocol in 14 consecutive cases. Thirteen patients (12 presenting one and one presenting two episodes of CAPS) were consecutively treated and monitored between 1986 and 2017. Antiphospholipid antibody (aPL) characteristics of the patients were compared with those of 64 matched controls (45 antiphospholipid syndrome patients and 19 aPL carriers) who did not develop CAPS during the same mean follow-up period (12 years ± 9.9 SD). Triple aPL positivity (IgG/IgM anticardiolipin + IgG/IgM anti-β2Glycoprotein I + lupus anticoagulants) significantly prevailed in the CAPS patients with respect to the controls (p = 0.003). IgG anticardiolipin and IgG anti-β2Glycoprotein I mean antibody titers of the CAPS patients were significantly higher than those of the controls (p = 0.0018 and p = 0.003, respectively). Triple therapy (anticoagulation + plasma exchange + steroids) was administered to all the CAPS cases except for one. Beginning in 2009, intravenous immunoglobulin infusion has also been included in the triple therapy protocol (six patients). All the patients recovered from CAPS; five showed renal failure and one a I-II class New York Heart Association (NYHA) dilated cardiomyopathy. Long-term outcomes of CAPS included a gradual worsening of renal failure in one patient who required hemodialysis 30 years after the acute episode. Renal function improved in the other four patients. The patient affected with dilated cardiomyopathy worsened to a II class NYHA over a five year period. Currently all the patients are alive. A specific antiphospholipid antibody profile could be considered a risk factor associated to CAPS. Early use of a defined treatment protocol based on triple therapy either or not associated with IVIG was associated with recovery in all CAPS patients. [ABSTRACT FROM AUTHOR]

Abstract The anti-phospholipid syndrome (APS) is a prothrombotic autoimmune disorder characterized by either thrombosis or pregnancy complications in the setting of persistent anti-phospholipid antibodies (aPL). βeta 2-glycoprotein I (β2-GPI) is the major autoantigen in APS that binds anionic phospholipids as well as specific receptors on platelets and endothelial cells resulting in activation of prothrombotic pathways. β2-GPI consists of 5 Domains that exist in a circular or linear form, with the latter occurring after binding to anionic phospholipids. β2-GPI also undergoes dynamic posttranslational modification between oxidized and free thiol forms. The relationship between posttranslational modification and structural conformation is yet to be definitively clarified. Compared with controls, patients with the APS have higher levels of total β2-GPI and lower levels of free thiol β2-GPI. This raises the possibility of using quantification of β2-GPI posttranslational modification as a redox biomarker in the management and diagnosis of the APS. Graphical abstract fx1 Highlights • βeta 2-glycoprotein I (β2-GPI) is the Antiphospholipid Syndrome major autoantigen. • β2-GPI exists in either a circular or “hockey stick-like” form. • β2-GPI undergoes posttranslational changes between oxidized and free thiol forms. • Antiphospholipid Syndrome patients have higher levels of total and oxidized β2-GPI. • Antiphospholipid Syndrome patients have lower levels of free thiol β2-GPI. [ABSTRACT FROM AUTHOR]

Background: While thrombopoeitin (TPO) agonists that act to simulate platelet production have been approved for use in steroid-refractory chronic immune thrombocytopenia purpura (ITP), there are few data on the safety and efficacy of these medications in patients with concurrent systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). Given that these agents can increase all hematopoietic cell lineages, it is unclear if there is an increased risk for exacerbation of the underlying lymphocyte-driven autoimmune disease in this population. Case summaries: This case series includes four patients with SLE, one with concurrent APS, who were treated for steroid-refractory ITP with TPO mimetics at the University of Virginia between 2005 and 2015. In three of the four cases the medication was successful in improving platelet counts and preventing bleeding events. In addition, none of the patients experienced thrombosis or worsening of their underlying autoimmune disease. Conclusions: This case series suggests that TPO mimetics are safe and moderately effective in patients with ITP in the setting of SLE or APS and do not contribute to increased disease activity. [ABSTRACT FROM AUTHOR]

Antiphospholipid Syndrome (APS) is a condition characterized by the occurrence of thromboembolic events and/or pregnancy loss combined with one laboratory criterion among Lupus Anticoagulant- LAC, anticardiolipin –aCL, and anti β2-Glycoprotein I -aβ2GPI antibodies. Several hypotheses were put forward to explain the causal role of antibodies in the clinical events but none is fully convincing. Current laboratory diagnosis is based on three tests (LAC, IgG/IgM aβ2GPI and IgG/IgM aCL antibodies). The triple-positive profile (all the three tests positive, same isotype) is associated with a higher risk for thrombosis. The mainstay of therapy in thrombotic APS is anticoagulation, with VKAs being the cornerstone. Low dose aspirin in combination or alone may have a role in arterial thrombosis, and in primary thromboprophylaxis. The Non-Vitamin K Antagonists Oral Anticoagulants (NOACs) role in the therapy of APS is under investigation but not verified. Alternative treatment options including rituximab and eculizumab have been successfully reported in few cases of catastrophic APS. [ABSTRACT FROM AUTHOR]

Objective To investigate miRNA expression in relation to transcriptomic changes in plasmacytoid dendritic cells (pDCs) in SLE and APS. pDCs are major producers of IFNα in SLE and APS, and miRNAs are emerging as regulators of pDC activation. Methods miRNA and mRNA expression were measured by OpenArray and RNA-sequencing in pDCs of SLE, SLE + APS (APS secondary to SLE) and primary APS (PAPS) patients. The miRNA profile of patients was compared with the miRNA pattern of TLR7-activated pDCs. Results Among 131 miRNAs detected in pDCs, 35, 17 and 21 had a significantly lower level of expression in SLE, SLE + APS and PAPS patients, respectively, as compared with healthy controls (HC). Notably, the miRNA profile did not significantly differ between SLE and APS, but was driven by the presence or absence of an IFN signature. TLR7 stimulation induced a general downregulation of miRNAs, similar to the pattern observed in SLE and APS patients. miR-361-5p, miR-128-3p and miR-181a-2-3p expression was lower in patients with a high IFN signature (false discovery rate <0.05) as compared with patients with a low IFN signature and HCs. Pathway enrichment on the overlap of miRNA targets and upregulated genes from the RNAseq indicated that these miRNAs are involved in pDC activation and apoptosis. Conclusion Lower miRNA expression in pDCs is shared between SLE, SLE + APS and PAPS and is related to the IFN signature. As pDCs are the alleged source of the IFN signature in these patients, a better understanding of the molecular mechanisms/pathways leading to pDC dysregulation in SLE and APS might open novel pathways for therapeutic intervention. [ABSTRACT FROM AUTHOR]

The catastrophic antiphospholipid syndrome (CAPS) is a life-threating variant of the antiphospholipid syndrome characterized by the development of multiple thrombosis in a short period of time, usually ending up in the failure of function of several vital organs. Most CAPS episodes are related to a prothrombotic situation or precipitating factor such as infections, surgical procedures or malignant diseases. In patients with CAPS, the development of multiple thrombosis leads to an important cytokine release that worsens the already critical patient's situation. The disease usually involves the kidneys, the lungs and the heart, although any organ system can be affected. Although occasionally the disease affects large vessels, in the majority of cases it affects small vessels, leading to a disseminated microangiopathic syndrome resembling thrombotic thrombocytopenic purpura. Treatment is based on the administration of anticoagulants, corticosteroids, plasma exchange and/or intravenous immunoglobulins. Cyclophosphamide is recommended in those CAPS cases associated to systemic lupus erythematosus. Additionally, rituximab and eculizumab have been used in refractory cases. Mortality is still around 30% despite current treatment. [ABSTRACT FROM AUTHOR]

Background: Prothrombotic state and impaired clot dissolution can contribute to the occurrence of chronic thromboembolic pulmonary hypertension in primary antiphospholipid syndrome. Pulmonary endarterectomy - the surgical removal of the organized thromboembolic material from the proximal pulmonary arteries - is the procedure of choice and potentially a curative option for patients with chronic thromboembolic pulmonary hypertension, including patients with antiphospholipid syndrome. We report an exceptionally severe and complicated case with favourable outcome. Case presentation: We present a case of a successful high risk pulmonary endarterectomy in a 29-year-old female with primary antiphospholipid syndrome and end-stage chronic thromboembolic pulmonary hypertension. Despite highly complicated perioperative course an impressive improvement in symptoms and functional status was achieved. Conclusion: We hope that this complicated but successfully managed case of a combination of two rare diseases will arouse earlier suspicion and timely diagnosis for such patients and will encourage physicians to promptly refer the suitable patients to a pulmonary endarterectomy team. It is important to remember that severe thrombocytopenia may occur in patients with antiphospholipid syndrome. [ABSTRACT FROM AUTHOR]

Objective: To elucidate clinical feature and anti-phospholipid antibody (aPL) profiles, including lupus anticoagulant (LA), anti-cardiolipin (CL) antibodies and anti-phosphatidylserine/prothrombin (PS/PT) antibodies, of pregnancy failure in patients with antiphospholipid antibody syndrome (APS) already treated with conventional therapy. Materials and methods: Thirty-four women with a history of pregnancy who were diagnosed with APS between 2008 and 2016 were included in the study. We defined the successful pregnancy group as women who gave birth to a healthy baby over 1500 g after 34 weeks of pregnancy under conventional treatment (heparin and/or low-dose aspirin). The unsuccessful pregnancy group was defined as women whose pregnancy outcomes did not meet the aforementioned criteria despite the conventional therapy. The clinical features and aPL profiles were compared between the two groups. Results: Fifteen women were classified into the unsuccessful pregnancy group; seven women were in the successful pregnancy group. Having history of both thrombosis and pregnancy morbidity and LA positivity were significantly more prevalent in the unsuccessful pregnancy group than in the successful pregnancy group (p <.05, respectively). In contrast, single positivity of anti-CL antibody was negatively associated with APS-associated pregnancy morbidity under the conventional treatment (p <.01). The proportion of anti-PS/PT IgG-positive patients was significantly higher in the unsuccessful pregnancy group (p = .02, OR 18.7, 95% CI 1.50, 232.29) with high concordance rate with LA (97% consistence). Conclusion: History of both thrombosis and pregnancy morbidity and the positivity of LA and/or anti-PS/PT-IgG, not but anti-CL-antibodies were correlated with APS-associated pregnancy morbidity refractory to conventional treatment. Clinical feature and aPL profiles might help us to make risk assessment for adverse pregnancy outcomes in patients with APS. [ABSTRACT FROM AUTHOR]

Recurrent thrombosis and miscarriages are the main clinical manifestations of antiphospholipid syndrome (APS). Although most patients display both clinical signs, some patients can have isolated vascular or obstetric variants. Emerging data raise the question of whether obstetric and vascular APS are the same or different diseases. An important difference between the two conditions is that a thrombophilic state is a common feature in vascular APS, whereas clot occlusions of the decidual spiral arteries are seldom observed in obstetric APS, and infarctions are found in only one-third of APS placentae. Conversely, inflammation, which is undetectable in vascular APS, is frequently observed in the placentae of patients with obstetric APS and has been documented in the placentae of pregnant mice with fetal loss mediated by antiphospholipid antibodies. Attempts to identify different antibodies or epitopes responsible for the two clinical manifestations of APS have so far been unsuccessful. Possible mechanisms exist that might explain the development of the two clinical presentations, including the tissue distribution and expression level of the main target antigen of antiphospholipid antibodies, β2 glycoprotein I (β2GPI). The identification of the factors that promote the onset of either obstetric or vascular APS has important diagnostic and therapeutic implications. [ABSTRACT FROM AUTHOR]

Objectives. The objective of this study was to assess the effect that triple therapy (anticoagulation plus CS plus plasma exchange and/or IVIGs) has on the mortality risk of patients with catastrophic APS (CAPS) included in the CAPS Registry. Methods. Patients from the CAPS Registry were grouped based on their treatments: triple therapy; drugs included in the triple therapy but in different combinations; and none of the treatments included in the triple therapy. The primary endpoint was all-cause mortality. Multivariate logistic regression models were used to compare mortality risk between groups. Results. The CAPS Registry cohort included 525 episodes of CAPS accounting for 502 patients. After excluding 54 episodes (10.3%), a total of 471 patients with CAPS were included [mean (S.D.) age 38.5 years (17); 68.2% female; primary APS patients 62%]. Overall, 174 (36.9%) patients died. Triple therapy was prescribed in 189 episodes (40.1%), other combinations in 270 (57.3%) and none of those treatments in 12 episodes (2.5%); the mortality rate in the three groups was 28.6, 41.1 and 75%, respectively. Triple therapy was positively associated with a higher chance of survival when compared with non-treatment [adjusted odds ratio (OR) = 9.7, 95% CI: 2.3, 40.6] or treatment with other combinations of drugs included in the triple therapy (adjusted OR = 1.7, 95% CI: 1.2, 2.6). No statistical differences were found between patients that received triple therapy with plasma exchange or IVIGs (P = 0.92). Conclusion. Triple therapy is independently associated with a higher survival rate among patients with CAPS. [ABSTRACT FROM AUTHOR]

Persistent serum positivity for antiphospholipid antibodies (aPL) is required to diagnose antiphospholipid syndrome (APS), an autoimmune disease characterized by recurrent vascular thrombosis and/or pregnancy morbidity. The current therapeutic management of patients with thrombotic APS aims at preventing recurrences and long-term complications by attenuating the procoagulant state. There is overall consensus to reserve moderate-intensity anticoagulation to aPL-positive patients with a previous venous thrombosis; the therapeutic options for those with a history of arterial event comprise antiplatelet agents and high-intensity anticoagulation. Unfortunately, thrombotic occurrencesmight occur despite adequate anticoagulation, carrying a significant burden of morbidity and mortality. The management of refractory thrombotic APS and catastrophic APS is still not clear, warranting the issue of recommendations. Vitamin-K antagonists are limited by significant side effects, and a careful weighting of risks and benefits should be performed to reserve the optimal treatment to each patient. To overcome these limitations, novel oral anticoagulants have been introduced in the market, but their efficacy in thrombotic APS has still to be unraveled. The poor safety profile and the scarce efficacy of drugs acting on the coagulation cascade explain why novel therapeutic approaches are currently under investigation, to identify pharmacological tools specifically counteracting aPL-mediated prothrombotic effects. [ABSTRACT FROM AUTHOR]

DNA vaccines have recently emerged as a therapeutic agent for treating autoimmune diseases, such as multiple sclerosis. Antiphospholipid antibody syndrome (APS) is an autoimmune disease characterized by β2-glycoprotein I (β2-GPI)-targeting antiphospholipid antibodies (APAs) and vascular thrombosis or obstetrical complications. To examine the therapeutic potential of a β2-GPI DNA vaccine, we administered a vaccine mixed with FK506 as an adjuvant to a mouse model of obstetric APS. First, the pCMV3-β2-GPI DNA vaccine, which encodes the full-length human β2-GPI gene, was constructed. Then, we administered the β2-GPI DNA vaccine in 0.1 ml of saline, mixed with or without 100 μg of FK506, intramuscularly to the mice on days 28, 35 and 42. Blood titers of the anti-β2-GPI antibody, platelet counts, activated partial thromboplastin times (aPTTs), and the percentage of fetal loss were measured. We also stimulated murine splenic T cells ex vivo with β2-GPI and determined the T helper cell proportion and cytokine secretion. The administration of the β2-GPI DNA vaccine mixed with FK506 reduced the blood IgG anti-β2-GPI antibody titers and suppressed APS manifestations in mice. The combination also suppressed interferon-γ and interleukin (IL)-17A secretion but increased the Treg cell proportion and IL-10 secretion in murine splenic T cells following ex vivo stimulation with β2-GPI. Our results demonstrated the therapeutic efficacy of a β2-GPI DNA vaccine and FK506 as an adjuvant in a murine model of obstetric APS. Possible mechanisms include the inhibition of Th1 and Th17 responses and the up-regulation of Treg cells. [ABSTRACT FROM AUTHOR]

Anti-phospholipid syndrome (APS) is an acquired pro-thrombotic autoimmune disease that predisposes to thrombotic events and/or obstetric complications, in the persistent presence of anti-phospholipid antibodies (aPL). Life long moderate-intensity anticoagulation is the option of choice for aPL-positive patients with a previous thrombosis; critical issues concern the management of those with a history of arterial event due to the high rate of recurrence. Alternatives comprise anti-platelet agents and high-intensity anticoagulation. Low dose aspirin (LDASA) and low molecular weight heparin provide the mainstay of the treatment of obstetric APS, allowing a birth rate in 70% of cases. The management of refractory APS, thrombotic as well as obstetric, is highly debated, but an increasing burden of evidence points towards the beneficial effects of multiple treatments. Similarly, a management envisaging multiple drugs (anticoagulation, steroids, plasma exchange and/or intravenous immunoglobulins) is the most effective approach in catastrophic APS. Asymptomatic aPL carriers are at higher risk of thrombotic and obstetric complications compared to the general population, thus potentially benefitting of a pharmacological intervention. LDASA and hydroxychloroquine can be considered as options, in particular in case of high risk aPL profile, concomitant cardiovascular risk factors or associated autoimmune disease. APS is apparently a simple condition, but its multifaceted nature requires a complex and tailored treatment. [ABSTRACT FROM AUTHOR]

Kidney damage is a well-recognized complication of the antiphospholipid syndrome (APS), either primary or systemic lupus erythematosus (SLE)-associated APS. Kidney involvement in APS involves a variety of manifestations, such as renal artery thrombosis or stenosis, renal vein thrombosis, allograft loss due to thrombosis after kidney transplantation, and injury to the renal microvasculature, also known as APS nephropathy. Biopsy in patients with APS nephropathy includes acute thrombotic microangiopathy lesions and chronic intrarenal vascular lesions such as interlobular fibrous intimal hyperplasia, arterial and arteriolar recanalizing thrombosis, fibrous arterial occlusion, and focal cortical atrophy. The most frequent clinical features are hypertension, microscopic hematuria, proteinuria (ranging from mild to nephritic levels), and renal insufficiency. It is uncertain whether antiphospholipid antibodies or other factors are implicated in the development of APS nephropathy, and whether it is driven mainly by thrombotic or by inflammatory processes. Experimental models and clinical studies of thrombotic microangiopathy lesions implicate activation of the complement cascade, tissue factor, and the mTORC pathway. Currently, the management of APS nephropathy relies on expert opinion, and consensus is lacking. There is limited evidence about the effect of anticoagulants, and their use remains controversial. Treatment approaches in patients with APS nephropathy lesions may include the use of heparin based on its role on complement activation pathway inhibition or the use of intravenous immunoglobulin and/or plasma exchange. Targeted therapies may also be considered based on potential APS nephropathy pathogenetic mechanisms such as B-cell directed therapies, complement inhibition, tissue factor inhibition, mTOR pathway inhibition, or anti-interferon antibodies, but prospective multicenter studies are needed to address their role. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome is a complex autoimmune disease, characterized by the presence of vascular thrombosis, obstetric, hematologic, cutaneous, and cardiac manifestations. Renal disease in patients with antiphospholipid syndrome was not recognized in the first descriptions of the disease, but later on, the renal manifestations of the syndrome have been investigated widely. Renal manifestations of antiphospholipid syndrome conform a wide spectrum of diverse renal syndromes. Hypertension is one of the most frequent, but less commonly recognized renal alteration. It can be difficult to control as its origin is renovascular. Renal vascular thrombosis can be arterial or venous. Other alterations are renal infarction and vascular thrombosis in arterial territories. Venous thrombosis can be present in primary and secondary antiphospholipid syndrome; it presents with worsening of previous proteinuria or de novo nephrotic syndrome, hypertension and renal failure. Antiphospholipid syndrome nephropathy is a vascular disease that affects glomerular tuft, interstitial vessels, and peritubular vessels; histopathology characterizes the renal lesions as acute or chronic, the classic finding is thrombotic microangiopathy, that leads to fibrosis, tubule thyroidization, focal cortical atrophy, and glomerular sclerosis. Antiphospholipid syndrome nephropathy can also complicate patients with systemic lupus erythematosus, and there is vast information supporting the worse renal prognosis in this group of patients with the classic histopathologic lesions. Treatment consists of anticoagulation, as for other thrombotic manifestations of antiphospholipid syndrome. There is some evidence of glomerulonephritis as an isolated lesion in patients with antiphospholipid syndrome. The most frequently reported glomerulonephritis is membranous; with some reports suggesting that immunosuppressive treatment may be effective. Patients with end stage renal disease commonly are positive for antiphospholipid antibodies, but it is not clear what is the role of aPL in this setting. Patients with vascular access may have complications in the presence of antibodies so that anticoagulation is recommended. Patients ongoing renal transplant with persistent antiphospholipid antibody positivity may have early and late graft failure. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: This study aimed to assess the efficacy of high‐dose i.v. immunoglobulin (HIVIg) therapy in pregnant women with antiphospholipid syndrome (APS) secondary to systemic lupus erythematosus with a history of pregnancy failure, despite receiving low‐dose aspirin plus unfractionated heparin therapy, of which condition being designated as “aspirin–heparin‐resistant APS” (AHRAPS). Methods: The HIVIg therapy (20 g/d, 5 days) was performed for the pregnancies of five women with AHRAPS. Results: Five of the eight pregnancies ended in live births. The gestational ages of delivery in four of the five pregnancies were extended, compared with previous pregnancies. The HIVIg therapy was considered to be successful for these four pregnancies. Excluding one pregnancy that ended in miscarriage with an abnormal chromosome karyotype of the villi, the HIVIg therapy was considered to be successful in four (57.1%) of the seven pregnancies of the women with AHRAPS. Although all the live newborns were prematurely delivered, no adverse effect of the HIVIg therapy was observed. Conclusions: The HIVIg therapy might be beneficial as an immune modifier for pregnant women with AHRAPS. However, the precise indication of which women with AHRAPS who should receive HIVIg therapy remains unknown. [ABSTRACT FROM AUTHOR]

Recurrent pregnancy loss (RPL) is a physical and mental burden for women. In Vietnam, exploring the cause of miscarriages is still a challenge to clinical physicians. We aimed to investigate the etiology of RPL in the National Hospital of Obstetrics and Gynecology in Vietnam from 2012 to 2014. The cross-sectional study included 301 pregnant women with a history of RPL. The patients were examined and offered medical testing to determine the cause(s). Based on the testing, we determined causation for (11.29%) patients who had positive scores on an antiphospholipid antibody test and who were subsequently successfully treated for their problem. [ABSTRACT FROM AUTHOR]

Background and purpose: The most common neurological manifestation of antiphospholipid syndrome (APS) is ischaemic stroke. Identifying patients with APS at high risk for developing any thrombotic event remains a major challenge. In this study, the aim was to identify predictive factors of ischaemic stroke in a cohort of primary APS (PAPS) patients who presented with new onset symptoms suggestive of acute stroke. Methods: This prospective multicentre study included 36 consecutive PAPS patients who presented with new onset symptoms suggestive of an acute stroke. Patients were prospectively followed up for 12 months. Results: In 10 (28%) out of 36 PAPS patients [mean age 41 years (SD 13.4), 70% female], the suspicion of an acute stroke was confirmed by brain magnetic resonance imaging. Sixty per cent of these patients were <50 years old. Eight of the 10 patients had a history of previous venous thrombosis and were receiving vitamin K antagonist (VKA), with international normalized ratio target 2–3; one patient had a history of a previous arterial event receiving treatment with VKA target international normalized ratio 2–3 plus low dose aspirin; and one patient had a history of previous pregnancy morbidity receiving only low dose aspirin. Time in the therapeutic range for patients receiving VKA was 77.7% (SD 6.6%). Hypercholesterolaemia was significantly higher in patients with confirmed stroke compared to those without (P < 0.05). Similarly, a significantly higher rate of anti‐β2 glycoprotein‐I (β2GPI) antibodies (immunoglobulin G/immunoglobulin M; P < 0.05) and higher adjusted global APS score (aGAPSS) values were found in patients with a confirmed stroke [mean aGAPSS 8.9 (SD 4.7) vs. mean aGAPSS 6.4 (SD 2.5); P < 0.05]. Conclusions: Patients with PAPS, including young patients, have a high risk of recurrent thrombosis despite anticoagulation treatment. A careful risk assessment is mandatory to identify patients at risk for recurrence. [ABSTRACT FROM AUTHOR]

Background: B-cell differentiation and B-cell tolerance checkpoints may be different in antiphospholipid syndrome (APS) from systemic lupus erythematosus (SLE) and can help to understand differences between them. Our aim was to define alterations of B-cell subsets in patients with primary APS (pAPS) and to compare them with SLE patients and healthy controls (HC). Methods: Cross-sectional study including three study groups: 37 patients with pAPS, 11 SLE patients, and 21 age- and gender-matched HC. We determined the frequencies of different B-cell subsets in peripheral blood naïve and memory compartments. In addition, we measured serum B cell-activating factor (BAFF) levels and circulating pro-inflammatory cytokines, such as IL-6, by commercial ELISA and CBA, respectively. Results: Patients with pAPS showed a lower percentage of immature and naïve B cells than patients with SLE (p = 0.013 and p = 0.010, respectively) and a higher percentage of non-switched memory B cells than patients with SLE (p = 0.001). No differences either in the percentage of switched memory cells or plasma cells were found among the different groups. Serum BAFF levels were higher in SLE patients than in healthy controls and pAPS patients (p = 0.001 and p = 0.017, respectively). A significant increase in the serum BAFF levels was also observed in pAPS patients compared to HC (p = 0.047). Circulating IL-6 levels were higher in SLE and pAPS patients than HC (p = 0.036 and p = 0.048, respectively). A positive correlation was found between serum BAFF and IL-6 levels in patients with SLE but not in pAPS (p = 0.011). Conclusions: Our characterization of peripheral blood B-cell phenotypes in pAPS demonstrates different frequencies of circulating B cells at different stages of differentiation. These differences in the naïve B-cell repertoire could explain the higher number and variety of autoantibodies in SLE patients in comparison to pAPS patients, especially in those with obstetric complications. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The objectives were to determine the frequency of in utero fetal death (IUFD) related to placental disorders and to assess the frequency of antiphospholipid antibodies syndrome (APS) among women referred to the internal medicine department. Methodology: A retrospective clinical study conducted in Rennes University Hospital, France. From January 2007 to December 2014, 53 women who presented an IUFD at 14 weeks or more of gestational age were included. The main cause for each IUFD was determined by expert agreement. Primary outcome was to analyze the final etiologies diagnosed and the prevalence of IUFD related to placental disorders. Secondary outcomes included the frequency of APS among patients with IUFD of placental origin and the pathological and clinical features associated with APS. Results: IUFD resulted from placental disorders in 36/53 (68%) patients, and remained unexplained in 11 cases (20.8%). Among the 36 patients with placental disorders, APS was diagnosed in five (13.9%) cases, and four (11.1%) patients were considered as having ‘non‐criteria’ APS. History of thrombosis (P = 0.001) and placental infarcts (P = 0.047) were significantly associated with APS. Conclusion: Placental disorders were the major cause for IUFD in patients who were referred to internal medicine specialists. Importantly, APS was seldom found in patients with placental disorders. Venous thromboembolism history and placental infarcts were both significantly associated with APS. Further studies are needed in order to deepen our understanding of the physiopathology of placental disorders and its underlying causes among non‐APS women, and to determine the best treatment regimen for future pregnancies. [ABSTRACT FROM AUTHOR]

The major treatment issues in Antiphospholipid Syndrome (APS) include the the prevention of first thrombosis, the treatment of acute thromboembolic manifestations, the choice of anticoagulation, the duration of anticoagulation and secondary thrombosis prevention. Anticoagulation should individualized to the patient and clinical setting. Clasical anti vitamin K antagonists, warfarin and acenocumoral, carry some risks and disadvantages. Direct thrombin inhibitor and direct anti-Xa inhibitors are currently available and were approved for the prevention of stroke and systemic embolism in patients with atrial fibrillation, for the treatment of deep vein thrombosis (DVT) and for the prevention of recurrent DVT and pulmonary embolism. Besides many case series reports, there are ongoing clinical trials testing their efficiency and safety in patients with APS. In this paper we reviewed the advantages, risks and disadvantages for the use of direct oral anticoagulants in this category of patients. [ABSTRACT FROM AUTHOR]

The article focuses on the treatment of antiphospholipid antibodies. Topics discussed include role of phospholipids in clotting the blood; use of anticardiolipin antibodies, anti-beta2-glycoprotein-I antibodies, and the lupus anticoagulant tests for analyzing the same; and impact of antibodies on clotting system.

The current mainstay of treatment in patients with thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation, mainly with Vitamin K antagonist agents. Some recently available studies have created new ground for discussion about the possible discontinuation of anticoagulation therapy in patients with a history of thrombotic APS in whom antiphospholipid antibodies (aPL) are not detected any longer (i.e. aPL seroconversion). We report the main points discussed at the last CORA Meeting regarding the issue whether or not anticoagulation can be stopped after aPL seroconversion. In particular, we systematically reviewed the available evidence investigating the clinical outcome of APS patients with aPL seroconversion in whom anticoagulation was stopped when compared to those in whom therapy was continued regardless the aPL profile. Furthermore, the molecular basis for the aPL pathogenicity, the available evidence of non-criteria aPL and their association with thrombosis are addressed. To date, available evidence is still limited to support the indication to stop oral anticoagulation therapy in patients with a previous diagnosis of thrombotic APS who subsequently developed a negative aPL profile. The identification of the whole risk profile for cardiovascular manifestations and possibly of a second level aPL testing in selected patients with aPL might support the eventual clinical decision but further investigation is warranted. [ABSTRACT FROM AUTHOR]