Treatment Of Antiphospholipid Syndrome Research Articles

Antiphospholipid Patients Admitted in the Intensive Care Unit: What Must The Rheumatologist Know?

Antiphospholipid syndrome (APS) is a rare systemic autoimmune disorder that can escalate into a 'thrombotic storm' called the catastrophic antiphospholipid syndrome (CAPS), frequently requiring ICU admission for multiple organ failure. This review aims to offer insight and recent evidence on critically-ill APS patients. The CAPS classification criteria define this condition as the involvement of at least three organs/systems/tissues within less than a week, caused by small vessel thrombosis, in patients with elevated antiphospholipid antibodies levels. These criteria do not encompass the full spectrum of critically-ill thrombotic APS patients and they need to be cautiously used for the bedside diagnosis of CAPS. Thrombocytopenia is the laboratory hallmark of CAPS, sometimes dropping below 20G/L, but a complete thrombotic microangiopathy pattern is infrequent. Anticoagulation is the pivotal treatment for APS and CAPS, associated with improved outcome. Triple therapy - the combination of anticoagulation, high-dose corticosteroids, and either plasma exchange or intravenous immunoglobulins - remains the standard treatment for CAPS patients. Eculizumab, an anti-C5 monoclonal antibody, may be useful in refractory patients. Despite significant progress, CAPS mortality rate remains high. Its diagnosis and management are complex, requiring a close multidisciplinary cross talk between APS specialists and intensivists.

Patients with antiphospholipid syndrome and a first venous or arterial thrombotic event: clinical characteristics, antibody profiles and estimate of the risk of recurrence.

Thrombosis in antiphospholipid syndrome (APS) involves in most cases the venous circulation. Why in some patients thrombotic APS affects the arterial circulation and in particular cerebral circulation is unknown. In previous studies, both patient characteristics and antiphospholipid antibody types and titers have been associated with arterial thrombosis. Aim of this study was to compare the clinical characteristics and laboratory findings of venous and arterial thrombotic APS from a large series of patients. Data were retrieved from the Start 2 antiphospholipid, a multicenter prospective register of long-term collected data from Thrombosis Centers in Italy. Of 167 patients with thrombotic APS, 114 (68 %) had a venous and 53 (32 %) had an arterial event as first clinical manifestation. Several clinical characteristics and risk factors were different among groups in univariate analysis. Using logistic regression analysis, reduced creatinine clearance and hyperlipidemia were independent variable for the occurrence of arterial APS. Notably, no difference in antiphospholipid antibody profiles and aβ2-Glycoprotein I levels were found between groups. A higher adjusted global antiphospholipid syndrome score (aGAPSS) was found in arterial group indicating a possible high recurrence rate in arterial APS. These data have pathophysiological and clinical implication since associated conditions might predispose patients to arterial rather than venous events and call to a close monitoring and treatment of arterial APS due to their increased tendency to recurrence.

A CLINICAL CASE OF CRITICAL ISCHEMIA OF THE LOWER LIMB DUE TO ANTIPHOSPHOLIPID SYNDROME IN A PATIENT WITH NEWLY DIAGNOSED SYSTEMIC LUPUS ERYTHEMATOSUS

Background. Antiphospholipid syndrome (APS) is a systemic autoimmune disease with a wide range of vascular and obstetric manifestations associated with thrombotic and inflammatory mechanisms initiated by antiphospholipid antibodies.
 Aims: to demonstrate an early onset of secondary APS in the newly diagnosed systemic lupus erythematosus, data literature analysis.
 Materials and methods. We analyzed the clinical case of the patient, similar clinical cases that were published, and the latest diagnostic criteria, and recommendations for the diagnosis, treatment, and prevention of APS.
 Description of the clinical case. The patient, 27 years old, was admitted to the Rheumatology department at Communal non-commercial institution "Olexandrivska Clinical Hospital" in April 2023 with complaints of phantom pain of the amputated toes of the right foot, chilliness of the hands and feet, and joint pain. 
 She has been ill since January 2021, and since then, she has had joint pain and discoloration of the skin of her fingers and feet in the cold. Significant worsening started in January 2022. The patient was hospitalized at the National Scientific Center of Surgery and Transplantology named after O.O. Shalimov, and the distal phalanges of the 1-3 toes of the right foot were amputated. As far as the patient previously had COVID-19, and took a combined oral contraceptive comprehensive differential diagnosis was carried out. The examination in the Rheumatology department revealed systemic lupus erythematosus according to diagnostic criteria ACR/EULAR 2019 and secondary antiphospholipid syndrome based on ACR/EULAR criteria 2023. The patient was prescribed hydroxychloroquine, methylprednisolone, nifedipine, iloprost, and warfarin. The patient was discharged in good condition and continues treatment ambulatory under rheumatologist control.
 Conclusion. This clinical case demonstrates the importance of a multidisciplinary approach in patients with APS. Patients with venous or arterial thrombotic events, especially young adults without risk factors, should be screened for antiphospholipid antibodies.

Preeclampsia and the Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is characterized by venous or arterial thrombosis and/or adverse pregnancy outcome in the presence of persistent laboratory evidence of antiphospholipid antibodies (aPLs). Preeclampsia complicates about 10-17% of pregnancies with APS. However, only early onset preeclampsia (<34 weeks of gestation) belongs to the clinical criteria of APS. The similarities in the pathophysiology of early onset preeclampsia and APS emphasize an association of these two syndromes. Overall, both are the result of a defective trophoblast invasion and decidual transformation at early gestation. Women with APS are at increased risk for prematurity; the reasons are mostly iatrogenic due to placental dysfunction, such as preeclampsia or FGR. Interestingly, women with APS have also an increased risk for preterm delivery, even in the absence of FGR and preeclampsia, and therefore it is not indicated but spontaneous. The basic treatment of APS in pregnancy is low-dose aspirin and low-molecular-weight heparin. Nevertheless, up to 20-30% of women develop complications at early and late gestation, despite basic treatment. Several additional treatment options have been proposed, with hydroxychloroquine (HCQ) being one of the most efficient. Additionally, nutritional interventions, such as intake of vitamin D, have shown promising beneficial effects. Curcumin, due to its antioxidant and anti-inflammatory properties, might be considered as an additional intervention as well.

Activation of Platelet mTORC2/Akt Pathway by Anti-β2GP1 Antibody Promotes Thrombosis in Antiphospholipid Syndrome.

Anti-β2GP1 (β2-glycoprotein 1) antibodies are the primary pathogenic antibody to promote thrombosis in antiphospholipid syndrome (APS), yet the underlying mechanism remains obscure. We aimed to explore the intracellular pathway that mediated platelet activation. Platelets were isolated from patients with APS and subjected to RNA sequencing. Platelet aggregation, the release of platelet granules, platelet spreading, and clot retraction were detected to evaluate platelet activation. We purified anti-β2GP1 antibodies from patients with APS and the total IgG from healthy donors to stimulate platelets with/without FcγRIIA (Fcγ receptor IIA) blocking antibody or Akt (protein kinase B) inhibitor. Platelet-specific Sin1 (stress-activated protein kinase-interacting protein) deficiency mice were established. The thrombus model of inferior vena cava flow restriction, ferric chloride-induced carotid injury model, and laser-induced vessel wall injury in cremaster arterioles model were constructed after administration of anti-β2GP1 antibodies. Combined RNA sequencing and bioinformatics analysis suggested that APS platelets exhibited increased levels of mRNA associated with platelet activation, which was in line with the hyperactivation of APS platelets in response to stimuli. Platelet activation in APS platelets was accompanied by upregulation of the mTORC2 (mammalian target of the rapamycin complex 2)/Akt pathway and increased levels of SIN1 phosphorylation at threonine 86. Anti-β2GP1 antibody derived from patients with APS enhanced platelet activation and upregulated the mTORC2/Akt pathway. Moreover, the Akt inhibitor weakened the potentiating effect of the anti-β2GP1 antibody on platelet activation. Notably, Sin1 deficiency suppresses anti-β2GP1 antibody-enhanced platelet activation in vitro and thrombosis in all 3 models. This study elucidated the novel mechanism involving the mTORC2/Akt pathway, which mediates the promotion of platelet activation and induction of thrombosis by the anti-β2GP1 antibody. The findings suggest that SIN1 may be a promising therapeutic target for the treatment of APS.

An update on the biologics for the treatment of antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPLs). Although anticoagulation is the primary treatment for APS, it fails in approximately 20-30% of obstetric APS cases and more than 30% of thrombotic APS cases. Therefore, there is a need for new, targeted treatments beyond anticoagulants. Biologics, such as rituximab and eculizumab, have been recommended for refractory catastrophic APS. This review focuses on the recent advancements in the pathogenesis of APS and explores the potential of targeted treatments, including eculizumab, rituximab, belimumab, daratumumab, obinutuzumab, and anti-TNF-α antibodies, for APS management.

Hydroxychloroquine as an Immunomodulatory and Antithrombotic Treatment in Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an acquired highly prothrombotic disorder in which thrombo-inflammatory antiphospholipid antibodies (aPL) cause thrombosis via multiple mechanisms, including endothelial damage and activation. Obstetric complications in APS are caused by placental thrombosis, inflammation and complement activation. Anticoagulation is poorly effective in some patients especially those with triple positive aPL who are at ~30% risk of thrombosis recurrence within 10 years. Increasing therapeutic anticoagulation intensity may be beneficial but leads to excess bleeding with serious complications, such as intracerebral haemorrhage. Nonetheless, anticoagulation is still the mainstay of treatment despite the autoimmune nature of APS. The antimalarial immunomodulatory drug hydroxychloroquine (HCQ) has been used for many years for the treatment of inflammatory rheumatic diseases. HCQ has complex pleiotropic mechanisms of action upon multiple cell types. The proposed biological processes that HCQ regulates support the hypothesis that it may be a successful adjunctive treatment in the prevention of recurrent thrombosis and pregnancy complications.

Bibliometric and altmetric analysis of research relating to antiphospholipid syndrome based on VOS viewer (2011-2021).

Antiphospholipid syndrome is an autoimmune disorder characterized by recurrent vascular thrombosis and pregnancy losses in the presence of persistently positive antiphospholipid antibodies. Bibliometric analysis and altmetric analysis are methods of analyzing academic productivity and influence. Currently, the assessment of antiphospholipid syndrome through the above analyses is lacking. This study investigated the quantity and quality of studies in the field of antiphospholipid syndrome and revealed the characteristics of worldwide productivity on this disease by the bibliometric analysis and altmetric analysis. The terms "APS," "antiphospholipid syndrome," "antiphospholipid-antibody syndrome," and "Hughes syndrome" were searched on the Web of Science Core Collection from January 1, 2011, to December 31, 2021. Original articles and reviews were selected. We set the filters as "English." A total of 1818 articles were retrieved from 68 countries, of which 20 met the criteria of major active countries. High-income countries contributed 1341 articles (73.48%). The number of articles annually increased significantly in the 10-year period (P < 0.001). The USA (253, 13.91%) was the most productive country. Adjusted by population, Serbia was top of the list. According to the gross domestic product analysis, Serbia ranked first. The most used keywords such as thrombosis and antiphospholipid antibodies were presented by keywords analyses. A content analysis found antithrombotic and anticoagulant therapy as research hotspots. A significant correlation was detected between average citations and altmetric attention scores (P = 0.002) and Mendeley readers count (P < 0.001). From 2011 to 2021, the number of global articles increased rapidly. Most papers came from high-income countries. The relationship between the bibliometric and altmetric analyses were basically consistent; therefore the two can prove/complement each other. Key points • We revealed the global productivity characteristics of the papers related to antiphospholipid syndrome by using the methods of bibliometric analysis and altmetric analysis. • We found the most selected articles that describe the treatment of antiphospholipid syndrome, especially antithrombotic and anticoagulant treatments, which may be the current research hotspot.

Anticoagulant Therapy in Patients with Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by the persistent positivity of antiphospholipid antibodies (aPLA) together with thrombosis or obstetrical complications. Despite their recognized predominant role, aPLA are not sufficient to induce the development of thrombosis and a second hit has been proposed to be necessary. The mainstay of treatment of APS is anticoagulant therapy. However, its optimal intensity in different presentations of the disease remains undefined. Moreover, decision on which patients with aPLA would benefit from an antithrombotic prophylaxis and its optimal intensity are challenging because of the lack of stratification tools for the risk of thrombosis. Finally, decision on the optimal type of anticoagulant drug is also complex because the central pathway responsible for the development of thrombosis is so far unknown and should be carried out on an individual basis after a careful evaluation of the clinical and laboratory features of the patient. This review addresses the epidemiology, physiopathology, diagnosis and management of thrombosis and obstetrical complications in APS, with a special focus on the role of direct oral anticoagulants.

Anticoagulation Practice, Recurrent Thrombosis, and Major Bleeding in Antiphospholipid Syndrome- a Multicentre Observational Study in the United Kingdom

Background Antiphospholipid syndrome (APS) is a highly prothrombotic acquired autoimmune disease characterised by thrombosis and/or pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPL).Anticoagulation is the mainstay of treatment for APS however risk of recurrence remains high especially in triple antibody positive patients. Recent clinical studies demonstrated that DOACs are not as effective as Vitamin K Antagonists (VKA) in patients with APS especially those who are triple positive. However, the use of DOACs in patients without triple positive aPL remains variable. Aims 1)To assess real-life anticoagulation practice in the UK 2)To assess the rates of recurrent thrombosis, major bleeding and minor bleeding (as per International Society of Thrombosis and Haemostasis) in patients with thrombotic APS Methods This was a multicentre observational study. Data was collected using a pre-designed standardised case record form via a secure online data entry platform (REDCap). Only patients age ≥18 years with confirmed diagnosis of APS were included in the study. Results The study included 500 patients with APS from 15 National Health Service (NHS) Trusts across the UK. The mean age was 52.9 (-/+ 15.94) years and 66.6% (333/500) were male. Frequency of single, double, and triple positivity for aPL were 36.4%, 32.6% and 31% respectively. Almost 40% of patients (37.3% , 187/500) had underlying autoimmune disease in addition to APS. Of the 500 patients, 92.2% (461/500) had at least one thrombotic event, 13.8% (69/500) had obstetric complications and 4.6% (23/500) had both thrombotic and obstetric complications. In patients with thrombotic APS, venous thrombosis occurred in 65.9% (304/461) patients, arterial thrombosis in 41.6% (192/461), and microvascular thrombosis in 4.8% (22/461) respectively. Almost all patients (99.8%; 460/461) with a thrombotic history were on anticoagulants (460/461). Of these 76.5% (352/460) were on VKAs whilst only 18.7% (86/460) were on DOACs. The rest of the patients were on low molecular weight heparin (3.5%) and fondaparinux (1.3%). Of the 342 patients on warfarin 207 patients 61% (207/342) had an INR target of 2.5 (2.0-3.0) , 10.5% (36/342) had a target of 3.0 (2.5-3.5) and 28.9% (99/343) had target INR of 4.0 (3.5-4.5). Additionally, 29.8% (102/342) of patients on anticoagulation were on antiplatelet treatment and 31.9% (109/342) patients were on Hydroxychloroquine (HCQ). Of the 155 patients with triple positive APS, 64.5% (100/155) were on warfarin and 20.6% (32/500) were on DOACs and the remainder on LMWH or fondaparinux. In those with arterial thrombosis, the vast majority were on warfarin 82.8% (159/192) with 5.2% (10/192) on a DOAC and a small minority on LMWH or fondaparinux. Of the 192 patients with arterial thrombus, 68 (19.8%) were triple positive aPL and of these 7.4% (5/68) were on a DOAC. Table 1 shows the baseline characteristics of the study group. Recurrence of thrombosis occurred in 41.6% (192/461), most frequently within 3 years of diagnosis (65.1%, 125/192). The frequency of major (Figure 1) and minor bleeding were 2.8% (13/461) and 3.2% (16/461) respectively. Dual or triple aPL status, smoking, hypertension, and ischaemic heart disease were significantly associated with recurrent thrombosis on univariate but not multivariate analysis, confirming a multifactorial contribution for thrombosis. In both univariate and multivariate analysis, increasing age was significantly associated with major bleeding [hazard ratio (HR) 1·05, 95% confidence interval (CI) 1.01-1·10; P = 0·022]. Notably, a higher target INR was associated with major bleeding. Conclusions In the largest UK study of APS to date we assessed anticoagulation practice, recurrent thrombosis rate and bleeding rate in this cohort. The frequency of recurrence of thrombosis in APS was as high as 41.6% (192/461) with most patients developing recurrence within the first 3 years of diagnosis. Frequency of major and minor bleeding were 2.8% (13/461) and 3.2% (16/461) respectively. Age was a significant contributor for major bleeding whilst thrombosis was multifactorial. Although VKA remains the main anticoagulant of use in patients with thrombotic APS, there are wide variations in the practice within the UK which are mostly, but not wholly, adherent to national guidelines especially in the context of triple positive thrombotic disease and arterial thrombosis. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Low dose versus standard dose rituximab for the treatment of antiphospholipid syndrome: A pilot study from a tertiary medical center

To investigate the therapeutic effects and safety of low-dose and standard-dose rituximab (RTX) in the treatment of antiphospholipid syndrome (APS). In this real-world study, we included 22 consecutive patients with APS who received RTX. Standard dose (SD) was defined as an overall dosage of RTX ≥ 1000mg in the induction period, and low dose (LD) was defined as an overall dosage of RTX <1000mg. Of included patients, 1 patients died, 2 patients withdrew and 19 patients completed 6-month follow-up. Nine patients received SD-RTX and 13 patients received LD-RTX, and elder patients [LD-RTX vs. SD-RTX: (49.1 ± 15.5) vs. (35.8 ± 12.3) years, p = 0.044] and patients with later-onset [LD-RTX vs. SD-RTX: (46.8 ± 16.3) vs. (31.3 ± 13.6) years, p = 0.029] were more frequently included in LD-RTX than SD-RTX. Following 6 month RTX treatment, 8 patients (42.1%) achieved complete remission, 8 patients (42.1%) achieved partial remission and 3 patients (15.8%) showed no remission. The titers of anticardiolipin antibodies [baseline vs. 6 months: 30.8 (10.7, 90) vs. 19.5 (2.45, 69.10) U/L, p = 0.023] and the levels of erythrocyte sedimentation rate [baseline vs. 6 months: 29 (6, 63) vs. '6 (3, 14) mm/h, p = 0.021] exhibited a significantly decrease in all APS patients. Remission rate and titers of anti-β2-glycoprotein I and lupus anticoagulant did not differ significantly between two groups. RTX might be a safe and effective option for patients with APS, and low dose confers equal efficacy as standard dose. Further cohort studies are needed to confirm our findings.

Research trends and frontiers on antiphospholipid syndrome: A 10-year bibliometric analysis (2012–2021)

Objectives: A growing body of studies related to antiphospholipid syndrome (APS) have been published in recent years. Nevertheless, there is a lack of visualized and systematic analysis in the literature on APS. Hence, this study sought to conduct a bibliometric analysis to identify research status and discover frontiers in the field. Methods: Articles and reviews concerning APS were acquired from the Web of Science Core Collection (WoSCC) database. CiteSpace, VOSviewer and a bibliometric online analysis platform were employed to conduct a visualization and knowledge-map analysis. Results: A total of 1,390 publications regarding APS were identified. Globally, Italy contributed the most publications. The University of Padua was the most productive institution. Lupus ranked first in both the most published and most co-cited journals. Savino Sciascia and Spiros Miyakis were the most prolific and most co-cited authors, respectively. "Vitamin K antagonists (VKA)" and "immunoglobulin A (IgA)" were current research foci. Burst analysis of keywords suggested that "neutrophil extracellular trap (NET)," "direct oral anticoagulant (DOAC)," "open label," "outcome," "hydroxychloroquine (HCQ)," and "arterial thrombosis (AT)" were significant future research frontiers. Conclusion: The scientific literature on APS has increased steadily in the past 10years. The clinical studies on the treatment and mechanism research of APS are recognized as promising research hotspots in the domain of APS. The research status and trends of APS publications from the bibliometric perspective can provide a practical guide and important reference for subsequent studies by researchers and physicians in the domain.

PEGylated Domain I of Beta-2-Glycoprotein I Inhibits Thrombosis in a Chronic Mouse Model of the Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disorder in which autoantibodies cause clinical effects of vascular thrombosis and pregnancy morbidity. The only evidence-based treatments are anticoagulant medications such as warfarin and heparin. These medications have a number of disadvantages, notably risk of haemorrhage. Therefore, there is a pressing need to develop new, more focused treatments that target the actual pathogenic disease process in APS. The pathogenic antibodies exert their effects by interacting with phospholipid-binding proteins, of which the most important is beta-2-glycoprotein I. This protein has five domains, of which the N-terminal Domain I (DI) is the main site for binding of pathogenic autoantibodies. We previously demonstrated bacterial expression of human DI and showed that this product could inhibit the ability of IgG from patients with APS (APS-IgG) to promote thrombosis in a mouse model. Since DI is a small 7kDa protein, its serum half-life would be too short to be therapeutically useful. We therefore used site-specific chemical addition of polyethylene glycol (PEG) to produce a larger variant of DI (PEG-DI) and showed that PEG-DI was equally effective as the non-PEGylated DI in inhibiting thrombosis caused by passive transfer of APS-IgG in mice. In this paper, we have used a mouse model that reflects human APS much more closely than the passive transfer of APS-IgG. In this model, the mice are immunized with human beta-2-glycoprotein I and develop endogenous anti-beta-2-glycoprotein I antibodies. When submitted to a pinch stimulus at the femoral vein, these mice develop clots. Our results show that PEG-DI inhibits production of thromboses in this model and also reduces expression of tissue factor in the aortas of the mice. No toxicity was seen in mice that received PEG-DI. Therefore, these results provide further evidence supporting possible efficacy of PEG-DI as a potential treatment for APS.

Care and Treatment for an Antiphospholipid Syndrome-Related Lower Limb Skin Ulcer Unhealed for 7 Years: A Case Report.

Antiphospholipid syndrome (APS) is a group of rare autoimmune diseases caused by antiphospholipid antibodies that is mainly associated with arterial or venous thrombosis and/or complications during pregnancy. Skin lesions occur in approximately 30% of APS patients as initial manifestations. However, previous studies have primarily focused on the treatment of APS rather than the management of skin lesions. Here, the authors report a case of an APS-related lower limb skin ulcer that had remained unhealed for more than 7 years. The difficulties in this case were the diagnosis of APS, the risk of bleeding during debridement, wound infection, biofilm formation, reduced venous return from the lower limbs, and compliance with compression therapy and follow-up. A three-step wound care regimen based on a multidisciplinary team approach resulted in effective control of APS and healing of the ulcer to the lower leg in 95 days. Over two follow-ups, there was no recurrence of the ulcer.

Recurrent Pregnancy Loss: reviewing therapeutic approaches

Objetive: to discuss recurrent pregnancy loss (RPL) causes and shed light on the current evidence in the management of each one. Methods: A comprehensive and non-systematic search of the theme was carried out through online databases (PubMed and Cochrane database), using the terms “recurrent pregnancy loss”, “treatment”, “genetic or chromosomal abnormalities”, “uterine factor”, “uterine septum”, “fibroid”, “myoma”, “cerclage”, “endocrine causes”, “polycystic ovary syndrome”, “thyroid”, “hypothyroidism”, “hyperprolactnemia”, “antiphospholipid syndrome”, “hereditary thrombophilia”, “inherited trombophilia”, “obesity”, “lifestyle”, “unexplained miscarriages”, “progestogens”, “vaginal progesterone”, “assisted reproductive technologies”, “in vitro fertilization”, preimplantation genetic screening”, “obstetric complications” and variants as keywords. Results: Couples with structural chromosomal rearrangements should be advised of the good reproductive prognosis after natural conception, so that in vitro fertilization plus preimplantation genetic diagnosis should not be offered as first-line treatment for them. Treatment of women with subclinical hypothyroidism may reduce the risk of miscarriage. Bromocriptine treatment can be considered in women with hyperprolactinemia. There is insufficient evidence to recommend metformin supplementation in pregnancy to prevent pregnancy loss in women with glucose metabolism defect. Treatment of Antiphospholipid Syndrome with low-dose aspirin started preconceptionally and heparin started after the first positive pregnancy test is recommended. The evidence to recommend the use of progesterone to improve live birth rate in women with RPL and luteal phase insufficiency is insufficient. Conclusion: The treatment for RPL should be directed to the cause of the miscarriages. Since the outcomes for most couples with unexplained RPL are favorable without treatment, therapy interventions that have not been proven are not recommended.

Managing Antiphospholipid Syndrome in Children and Adolescents: Current and Future Prospects.

Pediatric antiphospholipid syndrome (APS) is a rare acquired multisystem autoimmune thromboinflammatory condition characterized by thrombotic and non-thrombotic clinical manifestations. APS in children and adolescents typically presents with large-vessel thrombosis, thrombotic microangiopathy, and, rarely, obstetric morbidity. Non-thrombotic clinical manifestations are frequently seen in pediatric APS and may be present even before the vascular thrombotic events occur. We review insights into the pathogenesis of APS and discuss potential targets for therapy. The identification of multiple immunologic abnormalities in patients with APS reveals molecular targets for current or future treatment. Management strategies, especially for APS in adolescents, require screening for additional prothrombotic risk factors and consideration of counseling regarding contraceptive strategies, lifestyle recommendations, treatment adherence, and mental health issues associated with this autoimmune thrombophilia. The main goal of therapy in pediatric APS is the prevention of thrombosis. The management of acute thrombosis events in children and adolescents is the same as for primary APS, which involves isolated occurrences, and secondary APS, which is seen in association with another autoimmune disease, e.g., systemic lupus erythematosus. A pediatric hematologist should be consulted so other differential thrombophilic conditions can be eliminated. Therapy includes unfractionated heparin or low-molecular-weight heparin followed by vitamin K antagonists. Treatment of catastrophic APS involves triple therapy (anticoagulation, intravenous corticosteroid pulse therapy, and plasma exchange) and may include intravenous immunoglobulin for children and adolescents with this condition. New drugs such as eculizumab and sirolimus seem to be promising drugs for APS.

Comparing pregnancy outcomes in patients with criteria and non-criteria autoimmune disease: A systematic review.

Not all patients fulfil criteria for specific autoimmune rheumatic diseases (ARDs) and are then defined as having non-criteria (nc)ARD. It is uncertain whether well-recognised associations with adverse pregnancy outcomes in patients with criteria ARD also exist in patients with ncARD or undifferentiated connective tissue disease (UCTD). Therefore, we undertook a systematic review of the prevalence of adverse pregnancy outcomes in various ncARD and UCTD compared with criteria ARD to identify whether there are increased risks and to examine for any benefits of treatment. This study was conducted in accordance with the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. A systematic literature review was performed using online databases including Medline and PubMed from inception to the beginning of April 2021 using appropriate keywords for various ARD and pregnancy outcomes. After screening 665 articles, 36 articles were chosen for full text review and 15 selected for final analysis. There were eight studies of nc antiphospholipid syndrome (APS) of more than 7000 pregnancies and seven studies of UCTD of more than 1000 pregnancies. No studies of any other ncARD in pregnancy were identified. We found that patients with either ncAPS or UCTD seem to have an increased burden of poor pregnancy outcomes compared with the general population. Despite the heterogeneity and poor quality of the studies, we also noted that ncAPS and criteria APS patients may have similar rates of obstetric complications with standard and/or non-standard APS treatment regimens. Our findings of increased risks of poor pregnancy outcomes in patients with ncAPS or UCTD will be helpful for pre-pregnancy counselling and management of these patients in pregnancy and support their referral to specialist obstetric-rheumatology and obstetric-haematology clinics.

Management of patient with immune thrombocytopenia with antiphospholipid syndrome and monoclonal gammopathy of undetermined significance

Immune thrombocytopenia with antiphospholipid syndrome and monoclonal gammopathy of undetermined significance poses therapeutic dilemmas – whether we should modify the immune thrombocytopenia treatment in antiphospholipid syndrome, what is the influence of monoclonal gammopathy of undetermined significance on the course of immune thrombocytopenia and whether we should and how to prevent the progression of monoclonal gammopathy of undetermined significance to multiple myeloma.

Role of Direct Oral Anticoagulation Agents as Thromboprophylaxis in Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disorder that causes venous, arterial and small-vessel thrombosis, pregnancy loss, and premature birth. Cardiac valvular disease, renal thrombotic microangiopathy, thrombocytopenia, hemolytic anemia, and cognitive impairment are some of its other clinical symptoms. Antiphospholipid antibodies cause endothelial cells, monocytes, and platelets to become activated, as well as an increase in tissue factor and thromboxane A2. Complement activation might play a key function in pathogenesis.Long-term oral anticoagulation is used to treat thrombosis, and individuals having arterial episodes should be treated quickly. Patients with systemic lupus erythematosus (SLE), as well as those with solely obstetric antiphospholipid syndrome, should get primary thromboprophylaxis. Obstetric care is based on a combination of medical and obstetric high-risk management, as well as aspirin and heparin therapy. Possible supplementary therapy for this condition is hydroxychloroquine. Statins, rituximab, and novel anticoagulant medicines are all potential future treatments for non-pregnant individuals with antiphospholipid syndrome. We aim to review the role of direct-acting oral anticoagulants (DOACs) as thromboprophylactic drugs in the treatment of APS in this article.The treatment of venous thromboembolism has been transformed by a new class of DOACs. These drugs, such as rivaroxaban, function by inhibiting factor Xa directly. Not only do they have known anticoagulant actions, but they also obviate the need for dosage monitoring and modification, in contrast to warfarin.We conducted an exhaustive literature search of PubMed/MEDLINE and Google Scholar Indexes using the keywords “Antiphospholipid syndrome,” “thromboprophylaxis,” and “oral anticoagulants” up to September 2021. We found that DOACs have been shown to be non-inferior to warfarin in a variety of anticoagulation situations in a number of high-powered clinical studies. In many hypercoagulable conditions such as APS, DOACs are quickly establishing themselves as first-line therapy. This article is focused on comprehensively reviewing the mechanism of action of DOACs, their role as thromboprophylactic drugs, risks and complications of DOACs, and comparing their efficacy with the standard treatment protocol and warfarin.

O16 A diagnosis of BehÇet’s Disease with secondary antiphospholipid syndrome

O16 A diagnosis of BehÇet’s Disease with secondary antiphospholipid syndrome