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Antiphospholipid syndrome (APS) has been implicated in a range of neuropsychiatric presentations. However, there is a paucity of systematic studies on APS in psychiatry. This paper reports the clinical manifestations of APS that are relevant to psychiatrists. The aspects of APS pathogenesis, diagnosis, and treatment presented in this paper are based on a literature review. Treatment-resistant and atypical psychiatric illnesses, severe cognitive dysfunction, migraines, transient ischaemic attacks, and thromboembolic episodes, along with characteristic skin manifestations are the common clinical features of this syndrome. Antiphospholipid antibodies (aPL)may have a causal role in the development of some neuropsychiatric conditions. The existing criteria of APS may not apply to psychiatric patients, which may result in the underdiagnosis of APS in psychiatry. There is no evidence-based guidance available for the treatment of APS in patients with psychiatric symptoms. The treatment of APS with antithrombotic agents in case reports has been reported to yield dramatic improvements in complex and treatment-resistant cases. The possibility of a causal role of aPL in high-morbidity conditions, such as psychosis, depression, and dementia, requires the psychiatrist to be vigilant to the occurrence of this syndrome. There is an urgent need to conduct studies that elucidate the role of aPL in psychiatric presentations, identify patient characteristics, and consider whether new criteria with greater applicability in psychiatry are needed. [ABSTRACT FROM AUTHOR]

This paper reports one case of successfully treated patients suffering from a rare entity, the catastrophic antiphospholipid syndrome (CAPS). Management of this patient is discussed in detail. [ABSTRACT FROM AUTHOR]

Antiphospholipid Syndrome (APS) has been widely recognized as a risk factor for the recurrence of both thrombosis and pregnancy losses; however the optimal treatment of patients is debatable. The aim of this paper was to establish a consensus among experts on the treatment of APS in pregnancy. A questionnaire that described possible different clinical situations was sent to the International Advisory Board of the 10th International Congress on Antiphospholipid Antibodies. Sixteen experts from different medical branches and different geographic areas sent their replies. The consensus was that treatment for APS pregnant patients should be low molecular weight heparin (LMWH) and low dose aspirin (LDA). The dosage, and frequency of LMWH depends on different situations, including the body weight and past history. Patients with previous thromboses usually receive two injections per day. Warfarin can also be used from 14 to 34 weeks, for patients with previous stroke or severe arterial thromboses. The use of intravenous immunoglobulin (IVIG) seems to be restricted to patients with pregnancy losses despite conventional treatment. The experts usually advised barrier methods of contraception, intrauterine device (if the patient is not taking corticosteroids) or progestins. Oral contraception with oestrogens was usually avoided. [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]

Apoptosis has been reported to induce changes in the remodelling of membrane lipids; after death receptor engagement, specific changes of lipid composition occur not only at the plasma membrane, but also in intracellular membranes. This paper focuses on one important aspect of apoptotic changes in cellular lipids, namely, the redistribution of the mitochondria-specific phospholipid, cardiolipin (CL). CL predominantly resides in the inner mitochondrial membrane, even if the rapid remodelling of its acyl chains and the subsequent degradation occur in other membrane organelles. After death receptor stimulation, CL appears to concentrate into mitochondrial "raft-like" microdomains at contact sites between inner and outer mitochondrial membranes, leading to local oligomerization of proapoptotic proteins, including Bid. Clustering of Bid in CL-enriched contacts sites is interconnected with pathways of CL remodelling that intersect membrane traffic routes dependent upon actin. In addition, CL association with cytoskeleton protein vimentin was observed. Such novel association also indicated that CL molecules may be expressed at the cell surface following apoptotic stimuli. This observation adds a novel implication of biomedical relevance. The association of CL with vimentin at the cell surface may represent a "new" target antigen in the context of the apoptotic origin of anti-vimentin/CL autoantibodies in Antiphospholipid Syndrome. [ABSTRACT FROM AUTHOR]

Background: Antiphospholipid syndrome is an autoimmune disorder characterized by the presence of antiphospholipid antibodies and commonly presents with vascular thromboembolic phenomena, thrombocytopenia, and obstetric complications. Antiphospholipid syndrome can be classified as either primary or secondary to other connective tissue diseases. Dermatologic manifestations are common; however, non-vasculitic skin ulceration is an uncommon manifestation of antiphospholipid syndrome with limited treatment options.Case Presentation: In this paper we report the case of a 58-year-old white woman who developed necrotic abdominal wall ulcers 27 years after a diagnosis of secondary antiphospholipid syndrome associated with systemic lupus erythematosus. The ulcers developed despite our patient being on therapeutic anticoagulation with warfarin and were resistant to further increases in the intensity of anticoagulation. Management was further complicated due to reluctance on the part of our patient to switch over to injectable heparin.Conclusions: This case highlights a rare late dermatologic presentation of antiphospholipid syndrome, which responded poorly to conventional anticoagulation with warfarin. Current management is limited to experimental therapies and the role of newer anticoagulants is still unknown. [ABSTRACT FROM AUTHOR]

Abstract: The increased awareness of the role of humoral immunophysiology in antiphospholipid syndrome (APS) has aroused interest in B cells as therapeutic targets in this disease. This paper reviews the literature on B cell directed therapies in human and experimental APS. The clinical data is limited to B cell depletion with rituximab and comprises case reports and case series. Murine studies include use of modulators of B cell function such as belimumab and abatacept. In both human and murine studies, B cell directed therapies appeared to have clinical and serologic beneficial effects including a decrease in the antiphospholipid antibody titers after treatment. Randomized controlled clinical trials are needed to determine whether B cell depletors and/or B cell modulators can be effective agents for treating patients with APS. [Copyright &y& Elsevier]

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]

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]

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]

Conventional treatment of obstetric antiphospholipid syndrome fails in approximately 20–30% of pregnant women without any clearly identified risk factor. It is important to identify risk factors that are associated with these treatment failures. This study aimed to assess the impact of risk factors on pregnancy outcomes in women with obstetric antiphospholipid syndrome treated with conventional treatment. We carefully retrospectively selected 106 pregnancies in women with obstetric antiphospholipid syndrome treated with heparin + aspirin. Pregnancy outcomes were evaluated according to the following associated risk factors: triple positivity profile, double positivity profile, single positivity profile, history of thrombosis, autoimmune disease, more than four pregnancy losses, and high titers of anticardiolipin antibodies and/or anti-βeta-2-glycoprotein-I (aβ2GPI) antibodies. To establish the association between pregnancy outcomes and risk factors, a single binary logistic regressions analysis was performed. Risk factors associated with pregnancy loss with conventional treatment were: the presence of triple positivity (OR = 5.0, CI = 1.4–16.9, p = 0.01), high titers of aβ2GPI (OR = 4.4, CI = 1.2–16.1, p = 0.023) and a history of more than four pregnancy losses (OR = 3.5, CI = 1.2–10.0, p = 0.018). The presence of triple positivity was an independent risk factor associated with gestational complications (OR = 4.1, CI = 1.2–13.9, p = 0.02). Our findings reinforce the idea that triple positivity is a categorical risk factor for poor response to conventional treatment. [ABSTRACT FROM AUTHOR]

Background: The antiphospholipid syndrome (APS) is defined by simultaneous presence of vascular clinical events and antiphospholipid antibodies (aPL). The aPL considered as diagnostics are lupus anticoagulant and antibodies anticardiolipin (aCL) and anti-ß2 glycoprotein-I (aB2GP1). During recent years, IgA aB2GP1 antibodies have been associated with thrombotic events both in patients positive, and mainly negative for other aPL, however its value as a pro-thrombotic risk-factor in asymptomatic patients has not been well defined. Objective: To test the role of IgA anti B2GP1 as a risk factor for the development of APS-events (thrombosis or pregnancy morbidity) in asymptomatic population with a 5-year follow-up. Methods: 244 patients isolated positive for anti-beta2-glycoprotein I IgA (Group-1 study) and 221 negative patients (Group-2 control) were studied. All the patients were negative for IgG and IgM aCL. Results: During the follow-up, 45 patients (9.7%) had APS-events, 38 positive for IgA-aB2GP1 and 7 negative (15.6% vs 3.2%, p<0.001). The incidence rate of APS-events was 3.1% per year in IgA-aB2GP1 positive patients and 0.6% per year in the control group. Arterial thrombosis were the most frequent APS-events (N = 25, 55%) and were mainly observed in Group-1 patients (21 vs 4, p = 0.001). Multivariate analysis were shown as independent risk-factors for the development of APS-events, age, sex (men) and presence of IgA-aB2GP1 (odds ratio 5.25, 95% CI 2.24 to 12.32). Conclusion: The presence of IgA-aB2GP1 in people with no history of APS-events is the main independent risk factor for the development of these types of events, mainly arterial thrombosis. [ABSTRACT FROM AUTHOR]

Objective: A task force of scientists at the International Congress on Antiphospholipid Antibodies recognized that phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) might contribute to a better identification of antiphospholipid syndrome (APS). Accordingly, initial and replication retrospective, cross-sectional multicentre studies were conducted to ascertain the value of aPS/PT for APS diagnosis. Methods: In the initial study (eight centres, seven countries), clinical/laboratory data were retrospectively collected. Serum/plasma samples were tested for IgG aPS/PT at Inova Diagnostics (Inova) using two ELISA kits. A replication study (five centres, five countries) was carried out afterwards. Results: In the initial study (n=247), a moderate agreement between the IgG aPS/PT Inova and MBL ELISA kits was observed (k=0.598). IgG aPS/PT were more prevalent in APS patients (51%) than in those without (9%), OR 10.8, 95% CI (4.0-29.3), p<0.0001. Sensitivity, specificity, positive (LRþ) and negative (LR-) likelihood ratio of IgG aPS/PT for APS diagnosis were 51%, 91%, 5.9 and 0.5, respectively. In the replication study (n=214), a moderate/substantial agreement between the IgG aPS/PT results obtained with both ELISA kits was observed (k=0.630). IgG aPS/PT were more prevalent in APS patients (47%) than in those without (12%), OR 6.4, 95% CI (2.6-16), p<0.0001. Sensitivity, specificity, LRþand LR- for APS diagnosis were 47%, 88%, 3.9 and 0.6, respectively. Conclusions: IgG aPS/PT detection is an easily performed laboratory parameter that might contribute to a better and more complete identification of patients with APS. [ABSTRACT FROM AUTHOR]

Antiphospholipid Syndrome (APS) is an autoimmune disease characterized by recurrent thromboses and fetal losses with the presence of antiphospholipid antibodies. The main treatment to prevent recurrent thrombotic events is oral anticoagulation with vitamin K antagonist (VKA), which requires frequent monitoring and dosage adjustments. Outpatient anticoagulation monitoring has its limitations, such as patients spending long hours between the testing procedure and waiting for the results to be adjusted. To optimize this adjustment and to improve APS patients-doctors relationship, we developed a website to help monitor APS patients, called Antiphospholipid Syndrome On Cloud or APSOnCloud. To test it, since March 2014 to March 2016, we registered 20 patients with APS that have inserted 132 international normalized ratio (INR) values. Sixty two percent were out of range and it took on average 7 hours for the doctor in charge to adjust these values. The mean time in therapeutic range was 58.1%. Our preliminary experience in monitoring VKA oral anticoagulation on APSOnCloud suggests that patients with APS might benefit from this web-based monitoring. [ABSTRACT FROM AUTHOR]

High titer of anti-β2-glycoprotein I antibodies (anti-β2GPI Ab) plays a pathogenic role in antiphospholipid syndrome (APS). Numerous studies have focused on the pathological mechanism in APS; however, little attention is paid to the immune mechanism of production of anti-β2GPI antibodies in APS. Our previous study demonstrated that Toll-like receptor 4 (TLR4) plays a vital role in the maturation of bone marrow-derived dendritic cells (BMDCs) from the mice immunized with human β2-glycoprotein I (β2GPI). TLR4 is required for the activation of B cells and the production of autoantibody in mice treated with β2GPI. However, TLR4 provides a third signal for B cell activation and then promotes B cells better receiving signals from both B cell antigen receptor (BCR) and CD40, thus promoting B cell activation, surface molecules expression, anti-β2GPI Ab production, and cytokines secretion and making B cell functioning like an antigen presenting cell (APC). At the same time, TLR4 also promotes B cells producing antibodies by upregulating the expression of B-cell activating factor (BAFF). In this paper, we aim to review the functions of TLR4 in B cell immune response and antibody production in autoimmune disease APS and try to find a new way for the prevention and treatment of APS. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a prothrombotic disease characterized by thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (apL). Management of thrombosis is based on long-term oral anticoagulation and patients with arterial events should be treated aggressively. Primary thrombo-prophylaxis is recommended in patients with systemic lupus erythromatosus (SLE) and obstetric APS. Obstetric APS care is based on high-risk management and treatment with aspirin and heparin. Possible future therapies include statins, hydroxychloroquine, rituximab, and new anticoagulant drugs. Current research is focused on targeting components of the complement system, interfering with aPL–mediated cell activation and using tailored peptides to block the pathogenic subpopulation of aPL. [ABSTRACT FROM PUBLISHER]

In the antiphospholipid syndrome (APS), patients produce antiphospholipid antibodies (aPL) that promote thrombosis and adverse pregnancy outcomes. Current therapy with anticoagulation is only partially effective and associated with multiple complications. We previously discovered that aPL recognition of cell surface β2-glycoprotein I (β2-GPI) initiates apolipoprotein E receptor 2 (apoER2)-dependent signaling in endothelial cells and in placental trophoblasts that ultimately promotes thrombosis and fetal loss, respectively. Here we sought to identify a monoclonal antibody (mAb) to β2-GPI that negates aPL-induced processes in cell culture and APS disease endpoints in mice. In a screen measuring endothelial NO synthase (eNOS) activity in cultured endothelial cells, we found that whereas aPL inhibit eNOS, the mAb 1N11 does not, and instead 1N11 prevents aPL action. Coimmunoprecipitation studies revealed that 1N11 decreases pathogenic antibody binding to β2-GPI, and it blocks aPL-induced complex formation between β2-GPI and apoER2. 1N11 also prevents aPL antagonism of endothelial cell migration, and in mice it reverses the impairment in reendothelialization caused by aPL, which underlies the non-thrombotic vascular occlusion provoked by disease-causing antibodies. In addition, aPL inhibition of trophoblast proliferation and migration is negated by 1N11, and the more than 6-fold increase in fetal resorption caused by aPL in pregnant mice is prevented by 1N11. Furthermore, the promotion of thrombosis by aPL is negated by 1N11. Thus, 1N11 has been identified as an mAb that attenuates APS-related pregnancy complications and thrombosis in mice. 1N11 may provide an efficacious, mechanism-based therapy to combat the often devastating conditions suffered by APS patients. [ABSTRACT FROM AUTHOR]

Catastrophic antiphospholipid syndrome is a rare condition with high morbidity and mortality. We present a refractory case of catastrophic antiphospholipid syndrome with a view to highlight the importance of early identification and aggressive treatment of this condition. A 36-year-old female presented with clinical manifestations of multiorgan vascular occlusion with a known history of primary antiphospholipid syndrome. The presentation was on a background of a recent change of her long-term anticoagulation from warfarin to therapeutic low-molecular-weight heparin. Given that multiorgan involvement with 3 organ systems occurred nearly simultaneously, a diagnosis of probable catastrophic antiphospholipid syndrome was made. Prompt therapeutic anticoagulation, antiplatelet, and glucocorticoid therapy was commenced. Despite this, the patient continued to demonstrate clinical features concerning for ongoing small vessel occlusion necessitating aggressive immunomodulatory therapy in the form of intravenous immunoglobulin, plasma exchange, and rituximab. [ABSTRACT FROM AUTHOR]

Background: Retinal vein occlusion (RVO) is a common retinal vascular disease and it is one of the most frequently reported causes of visual damage and blindness in the elderly. The current study investigated the potential association between antiphospholipid antibodies (APLA) and RVO risk by conducting a meta-analysis of case–control studies. Methods: A systematic literature search of Pubmed and Embase databases was conducted in August 1st, 2014. Odds ratios (ORs) were used to evaluate the associations between APLA and the incidence of RVO. A random-effects model was obtained for the quantitative synthesis. Results: A total of 11 studies were included in this meta-analysis. A meta-analysis of all studies assessing the risk of RVO revealed that APLA was associated with a statistically increased risk of RVO incidence (OR = 5.18, 95% CI = [3.37, 7.95]). The association between anticardiolipin antibodies (ACA) and the risk of RVO was significant (n =8, OR = 4.59, 95% CI = [2.75, 7.66]). However, the association between lupus anticoagulants (LA) and risk of RVO was non-significant (n = 5, OR = 3.90, 95% CI = [0.99, 15.37]). No significant publication bias was found in the 11 selected studies. Conclusion: APLA was significantly associated with the risk of RVO. Advanced analyses showed that ACA rather than LA affected the risk of RVO. Additional well-designed and well-conducted epidemiological studies are required to further our understanding of the relationship between APLA and RVO risk. [ABSTRACT FROM AUTHOR]

The article looks at a research which focuses on complexity related to demonstration of an antiphospholipid antibody by the lupus anticoagulants (LA) assay in antiphospholipid syndrome (APS), an autoimmune disorder associated with hypercoagulability. Topics discussed include heparin neutralization for a prolonged partial thromboplastin time (PTT), coagulation testing characteristics and LA identification to culminate in less secondary testing and guide appropriate antithrombotic therapy.

Antibodies to prothrombin can be detected by ELISA using prothrombin coated onto irradiated plates (aPT) or the phosphatidylserine/prothrombin complex as antigen (aPS/PT) and they have been both related with the clinical manifestation of APS. Current evidence supports the concept that they belong to distinct populations of autoantibodies. Nevertheless, they can both be detected simultaneously in one patient.This mini-review will focus on data available on aPS/PT antibodies and their clinical utility in the diagnosis of APS. [ABSTRACT FROM PUBLISHER]

The article presents a study which assessed the prevalence of disease- and therapy-related organ damage and complications after 15 years of follow-up to a patient with primary antiphospholipid syndrome (PAPS). Reviewed were medical records obtained from thirty-five Caucasian patients followed prospectively for at least 15 years. Results indicated that organ damage occur at a significant proportion among patients with histories of arterial events, indicating the possibility of disease evolution.

Introduction: The presence of antiphospholipid antibodies (aPL) is associated with infections, drugs and autoimmune disorders. Those antibodies are also detected in approximately 5-20% of the healthy population. The presence of aPL can lead to the occurrence of thrombotic events or abortion, which define the antiphospholipid syndrome (APS). Aim: To evaluate the potential role of aPL in diagnosing APS in patients with localized scleroderma (LoS). Material and methods: Serum samples from 45 patients with various forms of LoS were examined. They were screened with the commercially-available immunodot assay Anti-Phospholipid 10 Dot (GA Generic Assays GmbH, Dahlewitz, Germany). A number of clinical and laboratory parameters, especially APS symptoms, were assessed in patients with positive aPL: arterial and venous thrombotic events, obstetric complications, thrombocytopenia and neurological symptoms. Results: The following profile of aPL IgG or IgM was obtained from patients with LoS: cardiolipin 15/45, phosphatidic acid 41/45, phosphatidyl-choline 0/45, -ethanolamine 6/45, -glycerole 1/45 (patient with Lyme disease), -inositol 7/45, -serine 14/45, annexin V 34/45, β2GPI 21/45, prothrombin 30/45. Antiphospholipid antibodies profile screening in these individuals revealed two cases of suspected secondary laboratory APS. However, no such clinical and laboratory parameters were found in other LoS patients with positive aPL. Similarly, no association was found between the presence of aPL and either thrombotic events or other APS symptoms. Conclusions: Antiphospholipid antibodies are commonly found in patients with LoS but the exact role of these antibodies remains unclear. Clinical manifestations of APS are not frequently seen during LoS. [ABSTRACT FROM AUTHOR]

Normal pregnancy is associated with extensive changes in hemostasis such that the procoagulant effect becomes dominant. The evolutionary advantage of this hypercoagulability may be to counteract the inherent instability associated with hemochorial placentation, which is unique to human beings. However, overall, there is a four- to 10-fold increased thrombotic risk throughout gestation and the postpartum period. Certain inherited or acquired thrombophilic factors may predispose to arterial and/or venous thrombosis and have a possible association with pregnancy complications, including recurrent miscarriage (RM), which affects up to 5% of couples with childbearing desire. A subgroup of women with RM has been demonstrated to be in a prothombotic state before and after pregnancy. The long-term health implications of this hypercoagulability may imply an increased risk of ischemic heart disease. Moreover, the presence of antiphospholipid antibodies rather than thrombophilic genetic defects (i.e., factor V Leiden or prothrombin G202010A mutation) in patients with RM is a determinant of thrombotic events later in life, especially among those patients having also cardiovascular risk factors. This article highlights the thromboembolic risk in nonpregnant RM patients in different thrombophilic settings and the need for thromboprophylaxis among these patients. [ABSTRACT FROM AUTHOR]

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have poor prognosis, and pulmonary endarterectomy (PEA) is considered the treatment of choice for this condition. We report a case and review the literature of successful PEA for CTEPH due to antiphospholipid syndrome associated with systemic lupus erythematosus. The definitive and decisive approach needed to treat this high-risk patient with a history of comorbidity, long-term illness and poor compliance was found with a therapy of PEA. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluates the existing clinical evidence and new trends in treatment of women with refractory obstetric antiphospholipid syndrome (OAPS). The study adopts a non-systematic but comprehensive literature search with the use of important keywords from different computerized medical databases from January 2000 to March 2012. Results show that up to 20% of patients do not received recommended therapy.

Background: Antiphospholipid antibodies (aPLs) have been associated with thrombosis in the antiphospholipid antibody syndrome (APS) and with atherosclerotic vascular events in patients without APS.We examined the significance of aPLs in transient ischemic attack (TIA). Patients/methods: Patients with TIA <48 h from symptom onset were prospectively enrolled. Traditional aPLs, including anticardiolipin and β2-glycoprotein-I (β2GPI), and newer aPLs, including anti-phosphatidylserine/prothrombin (aPS/PT), β2GPI Domain 4/5 and β2GPI Domain 1 were measured. Primary outcome was a composite of stroke or death within 90 days or identification of a high risk stroke mechanism. Secondary outcomes were stroke or death and the presence of clinical/sub-clinical atherosclerosis. Results: Over 4.5 years, 167 patients were enrolled. Forty one patients (25%) had the composite endpoint. Antibodies were measured in 158 subjects. aPS/PT IgG antibodies were significantly associated with stroke/death (OR 16.3, 95% CI 2.3-116.7, p D0.005) and were non-significantly associated with the composite endpoint (OR 4.7, 95% CI 0.8-29.2, p D0.10). In multivariate analysis adjusting for ABCD2 risk score, aPS/PT IgG remained associated with stroke/death (OR 15.7, 95% CI 2.0-125.6, p D0.009). Other aPLs were not associated with clinical outcome and no association between APLs and atherosclerosis was identified. Conclusion: In contrast to other aPLs, aPS/PT IgG antibodies are independently associated with stroke or death in patients with TIA [ABSTRACT FROM AUTHOR]

Persistently positive antiphospholipid antibodies in association with thromboses and/or pregnancy morbidity is the hallmark of the antiphospholipid syndrome. The management of antiphospholipid antibody-positive patients has been focused on utilizing anti-thrombotic medications such as heparin or warfarin. Given that our understanding of the molecular mechanisms of antiphospholipid antibody-mediated thrombosis has been growing, it is highly likely that the current 'anti-thrombotic' approach to these patients will be replaced by an 'immunomodulatory' approach in the near future. This review article will address the experimental and/or clinical evidence behind some of these potential 'immunomodulatory' approaches (tissue factor inhibition, P38 mitogen-activated protein kinase inhibition, nuclear factor-κB inhibition, platelet glycoprotein receptor inhibition, hydroxychloroquine, statins, inhibition of β2GPI and/or anti-β2GPI binding to target cells, complement inhibition, and B cell inhibition) in antiphospholipid syndrome. [ABSTRACT FROM AUTHOR]

Thrombotic events associated with antiphospholipid (aPL) antibodies can be the first manifestation of malignancy. The pathologic significance of aPL antibodies in patients with malignancies, however, is still unclear. It remains an unresolved issue as to whether the presence of aPL antibodies may be considered as an "epiphenomenon" of the malignancy itself or whether it contributes directly to the development of thrombosis in these patients. In particular, solid tumors may be associated with the development of aPL antibodies, enhancing the thrombophilic risk in these patients. In general, routine anticoagulant prophylaxis with low-molecular-weight heparin in cancer patients with positive aPL antibodies is strongly indicated. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) in patients suffering from the antiphospholipid syndrome (APS) has been reported in almost any location of the vessel tree and the risk of recurrences has been found in several studies to be more closely associated with the presence of lupus anticoagulant than with the positivity for anti-cardiolipin antibodies. The thrombophilic state of APS raises the problem of the secondary prophylaxis to avoid VTE recurrences. For APS patients with VTE, published data appear to support a longer warfarin treatment if compared with the standard management of anti-phospholipid (aPL)-negative patients with VTE. The question of how long oral anticoagulant treatment should be continued for APS patients, however, remains unanswered. Concerning the intensity of anticoagulation, several authors recommend a target international normalized ratio (INR) between 3.0 and 4.0 to efficiently protect from VTE recurrences. A recent decision analysis study does support such a suggestion. On the contrary, in a few prospective studies regimens with lower target INRs appear to be effective, and some authors therefore recommend a target INR of between 2.0 and 3.0. Specific large and prospective trials are needed to address this question. Until such information becomes available, individualized treatment according to the patient's individual risk factors for both bleeding and thrombosis is the general practice. [ABSTRACT FROM AUTHOR]

Activation of the complement cascade is an important mechanism for antiphospholipid antibody-mediated thrombosis. We examined the effects of rEV576 (coversin), a recombinant protein inhibitor of complement factor 5 activation, on antiphospholipid antibody-mediated tissue factor up-regulation and thrombosis. Groups of C57BL/6J mice (n = 5) received either IgG from a patient with antiphospholipid syndrome (APS) or control IgG from normal human serum (NHS). Each of these groups of mice had IgG administration preceded by either rEV576, or phosphate buffer control. For each of the four treatment groups, the size of induced thrombus, tissue factor activity in carotid homogenates, anticardiolipin and anti-β2glycoprotein I (anti-β2GPI) levels were measured 72 h after the first injection. Mice treated with IgG-APS had significantly higher titers of anticardiolipin antibodies and anti-β2GPI at thrombus induction compared with those treated with IgG-NHS. The IgG-APS/phosphate buffer treatment induced significantly larger thrombi and tissue factor activity compared with other groups. Mice treated with IgG-APS/rEV576 had significantly smaller thrombi and reduced tissue factor activity than those treated with IgG-APS/phosphate buffer. The data confirm involvement of complement activation in antiphospholipid antibody-mediated thrombogenesis and suggest that complement inhibition might ameliorate this effect. [ABSTRACT FROM PUBLISHER]

International standards for anti-beta2 glycoprotein I (anti-β2GPI) testing are needed. We evaluated the suitability of polyclonal/monoclonal candidate reference materials (RM) for the assay. IgG/IgM anti-β2GPI were affinity-purified (AP) from high-positive antiphospholipid syndrome sera and IgG from HCAL clone supernatant. Igs were tested for purity by SDS-PAGE, pooled, concentrated, sterile-filtered and the protein concentration determined. One unit was defined as the binding activity of 1 µg/ml of AP anti-β2GPI Ig. IgG/IgM RM were each assigned a unit value using the respective AP material as a calibrator. Polyclonal/monoclonal RM and 30 samples were evaluated for linearity, unit equivalency and commutability. Polyclonal AP material was assigned a value of 100 U IgG and 15 U IgM anti-β2GPI, respectively. IgG-RM had a value of 270 IgG and the IgM-RM of 220.3 IgM anti-β2GPI U. The linearity (R2) of each RM curve for the various assays ranged from 0.96 to 0.99. Commutability samples fit very well within 95% prediction intervals and had excellent correlation when comparing assays. IgG and IgM polyclonal and IgG monoclonal RM displayed excellent linearity and commutability, being good candidates for better standardization of anti-β2GPI immunoassays. [ABSTRACT FROM PUBLISHER]

The 8th edition of the International Congress on Autoimmunity took place in the beautiful and historical city of Granada, Spain, from 9 to 13 March 2012. It gathered more than 2350 participants from 71 different countries, including internists, immunologists, rheumatologists, basic researchers and many other clinicians and laboratory people interested in autoimmune diseases who were updated with the latest available diagnostic tools and new therapeutic avenues. This top international autoimmunity meeting put together an international faculty of more than 100 experts to present a high-level scientific program under the leadership of Professor Yehuda Shoenfeld (Zabludowicz Center for Autoimmune Diseases, Tel-Hashomer, Israel) who chaired the congress together with Ricard Cervera (Hospital Clínic, Barcelona, Catalonia, Spain), Angela Tincani (University of Brescia, Italy) and Carlos Vasconcelos (Hospital S. António, Porto, Portugal) as co-chairpersons. [ABSTRACT FROM AUTHOR]

IgA anti-beta2-glycoprotein I (IgA-aB2GPI) antibodies are currently not included as a laboratory criterion of antiphospholipid syndrome (APS). In the 13th International Congress on Antiphospholipid Antibodies, Galveston, TX, (USA) in 2010, these antibodies were accepted as an APS laboratory criterion in patients who had clinical manifestations of APS but were negative for ''consensus'' antiphospholipid antibodies (aPL) (IgG and IgM isotypes). Consequently, individuals with thrombotic events who are negative for consensus aPL may be undiagnosed for APS. The most recent publications have confirmed that IgA-aB2GPI antibodies are a risk factor for thrombotic events. In this viewpoint, we propose that IgA-aB2GPI antibodies should be included as an APS consensus criterion and that we have to help Cinderella become a princess. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including the obstetric, general clinical, and basic issues concerning antiphospholipid antibodies.