Search

BackgroundReports of severe COVID-19 being associated with thrombosis, antiphospholipid antibodies (APLA), and antiphospholipid syndrome have yielded disparate conclusions. Studies comparing patients with COVID-19 with contemporaneous controls of similar severity are lacking.Methods22 COVID-19+ and 20 COVID-19– patients with respiratory failure admitted to intensive care were studied longitudinally. Demographic and clinical data were obtained from the day of admission. APLA testing included anticardiolipin (aCL), anti-β2glycoprotien 1 (β2GP1), antidomain 1 β2GP1 and antiphosphatidyl serine/prothrombin complex. Antinuclear antibodies (ANAs) were detected by immunofluorescence and antibodies to cytokines by a commercially available multiplexed array. Analysis of variance was used for continuous variables and Fisher’s exact test was used for categorical variables with α=0.05 and the false discovery rate at q=0.05.ResultsAPLAs were predominantly IgG aCL (48%), followed by IgM (21%) in all patients, with a tendency towards higher frequency among the COVID-19+. aCL was not associated with surrogate markers of thrombosis but IgG aCL was strongly associated with worse disease severity and higher ANA titres regardless of COVID-19 status. An association between aCL and anticytokine autoantibodies tended to be higher among the COVID-19+.ConclusionsPositive APLA serology was associated with more severe disease regardless of COVID-19 status.Trial registration numberNCT04747782

Background Systemic lupus erythematosus (SLE) may have a different serological and clinical profile according to age of disease onset. Aim To compare clinical presentation and serological data from patients with SLE onset in childhood (cSLE) with disease onset in adulthood (aSLE) in a sample of Brazilian patients. Methods Retrospective study of 614 SLE patients from a single Rheumatology Unit from Brazil: 77 (12.5%) cSLE and 537 (87.4%) aSLE. Clinical and serological data were obtained from the charts. Comparisons of cSLE with aSLE in general and according to patient’s gender were made. Results The comparison of whole sample showed that children had more malar rash (p = 0.04), seizures (p Conclusion Children had a higher frequency of severe manifestations (glomerulonephritis and central nervous system) than adults. The difference in glomerulonephritis occurrence disappeared when only males were compared.

Involuntary movement disorders are rare in childhood. Hyperkinetic movement disorders including chorea stand as the leading cause. Although Sydenham chorea is the major diagnosis in most children and adolescents, appropriate differential diagnosis is fundamental for a final decision. A detailed and careful history as well as physical examination is the principal proceeding for accurate diagnosis. Herein, we report on an adolescent girl who was admitted to our hospital with chorea and subsequently diagnosed with systemic lupus erythematosus (SLE). Accompanying joint complaints in the patient's history, including growth retardation noticed during a physical examination and bicytopenia recognized in laboratory evaluation, increased the suspicion of SLE rather than Sydenham chorea in the patient. Central nervous system involvement defined as neuropsychiatric lupus presents wide clinical findings varying from stroke and seizures to psychosis and cognitive dysfunction. Although disease activity, persistently positive anticardiolipin antibodies, and lupus anticoagulant positivity are reported to be the most important risk factors in neuropsychiatric lupus, they are not always directly correlated. We present this patient in order to draw attention to the importance of physical examination and history in the differential diagnosis of chorea in childhood.Unwillkürliche Bewegungsstörungen im Kindesalter sind selten. Die häufigste Ursache sind hyperkinetische Bewegungsstörungen, einschließlich Chorea. Obwohl die Sydenham-Chorea bei den meisten Kindern und Jugendlichen die Hauptdiagnose darstellt, ist eine angemessene Differenzialdiagnose für eine endgültige Entscheidung von grundlegender Bedeutung. Eine detaillierte und sorgfältige Anamnese sowie eine körperliche Untersuchung sind die wichtigsten Voraussetzungen für eine genaue Diagnose. In diesem Beitrag berichten wir über ein jugendliches Mädchen, das mit Chorea in unser Krankenhaus eingeliefert wurde und bei dem anschließend ein systemischer Lupus erythematodes (SLE) diagnostiziert wurde. Begleitende Gelenkbeschwerden in der Anamnese, eine bei der körperlichen Untersuchung festgestellte Wachstumsverzögerung und eine bei der Laboruntersuchung festgestellte Biztopenie verstärkten den Verdacht auf SLE und nicht auf eine Sydenham-Chorea bei der Patientin. Eine Beteiligung des zentralen Nervensystems, die als neuropsychiatrischer Lupus definiert wird, weist ein breites klinisches Spektrum auf, das von Schlaganfällen und Krampfanfällen bis hin zu Psychosen und kognitiven Funktionsstörungen reicht. Obwohl die Krankheitsaktivität, anhaltend positive Anticardiolipin-Antikörper und eine Positivität auf Lupus-Antikoagulanzien als die wichtigsten Risikofaktoren für neuropsychiatrischen Lupus gelten, besteht nicht immer eine direkte Korrelation. In diesem Artikel wird dieser Patient vorgestellt, um auf die Bedeutung der körperlichen Untersuchung und der Anamnese bei der Differenzialdiagnose von Chorea im Kindesalter aufmerksam zu machen.

Objective To determine the efficacy of antibody typing and treatment on live birth rate in Chinese patients with antiphospholipid syndrome (APS)-related recurrent spontaneous abortion (RSA). Methods A retrospective study analyzed 4542 Chinese patients who experienced spontaneous abortion, of whom 314 had APS (272 primary and 42 secondary). Type of antibodies was tested. Anticoagulant and anti-inflammatory treatments were adopted according to the titer and type of antibodies. The incidence of repeated abortion and placental dysfunction, gestational age, and mean weight of the fetuses were recorded. Results Among the patients with APS-related RSA, primary APS accounted for the largest proportion. The proportion of antibody classification was as follows: β2-glycoprotein 1 (β2GP1)-IgM (151, 48.08%), lupus anticoagulant (LAC) (36, 11.46%), anticardiolipin (aCL)-IgM (32, 10.19%), β2GP1-IgM and aCL-IgM (29, 9.23%), and aCL-IgG (16, 5.09%). After treatment, the negative conversion of antibody, including β2GP1-IgM and LAC, significantly improved pregnancy outcomes. There was no significant difference in pregnancy outcomes between the other antibody titers. Conclusion The combination of anticoagulant and anti-inflammatory treatment led to a higher live birth rate in the treatment of APS-related RSA, highlighting the potential of antibody typing in providing clinical guidance for the treatment of APS-related RSA.

Introduction Besides distinctive respiratory and digestive hallmarks, COVID-19 has been recently associated with a high prevalence of pro-inflammatory and hypercoagulable states known as “COVID-19 Associated Coagulopathy” (CAC), corresponding to a worsening in patients’ conditions, whose causes are still to be elucidated. A link between anti-phospholipid antibodies (aPLs) and viral infections has long been suggested. APLs are assessed for anti-phospholipid syndrome (APS) diagnosis, characterized by thrombocytopenia, thrombosis, and coagulopathy. Furthermore, circulating immune complexes (CICs), arisen upon inflammatory responses and related immune dysregulation, can lead to endothelial cell damage and thrombotic complications. Method We performed an extended panel including IgG/IgM anti-cardiolipin, IgG/IgM anti-β2-glycoprotein-1, coupled with IgG/IgM anti-prothrombin, IgG/IgM anti-annexin-V on two COVID-19 patient groups (early and late infection time), and a negative control group. IgG CIC analysis followed to evaluate inflammatory status, through a possible complement system activation. Results Our results showed low positive case percentage in IgG/IgM anti-cardiolipin and IgG/IgM anti-β2-glycoprotein-1 assays (4.54%, 6.25%, and 4.55%; in early infection group, late infection group, and control group, respectively); few positive cases in IgG/IgM anti-prothrombin and IgG/IgM anti-annexin-V immunoassays; and no IgG CIC positivity in any patient. Conclusions In conclusion, our data show a low aPL prevalence, likely excluding an involvement in the pathogenesis of CAC. Interestingly, IgG/IgM anti-prothrombin and anti-annexin-V positive cases, detected in late infection group, suggest that aPLs could temporarily increase or could trigger a “COVID-19-induced-APS-like-syndrome” in predisposed patients. Key Points•To our knowledge, anti-prothrombin (aPT) antibodies, anti-annexin-V antibodies and CICs in COVID-19 patients have not been reported in the scientific literature.•Lack of uniformity and the low percentage of aCL/aβ2GP1 positivity preclude a putative role in CAC pathogenesis.•IgG/IgM anti-prothrombin and IgG/IgM anti-annexin-V data show that distribution of positive case number increases in late infection patients, significantly in anti-annexin-V results, suggesting a possible role for these anti-phospholipid antibodies in disease course.•aPLs can arise transiently in some patients with critical illness and SARS-CoV-2 infection (disappearing in a few weeks), as well as in other genetically predisposed patients; they could trigger a “COVID-19-induced-APS-like-syndrome”.

Aim To evaluate the clinical relevance of antiphospholipid antibodies (aPL) in patients with lower extremity peripheral artery disease (PAD). Data sources EMBASE and MEDLINE databases were searched from inception to March 2020 for clinical studies reporting on the association between of aPL [IgG/IgM anticardiolipin (aCL) and lupus anticoagulant (LA)] and PAD. Methods We determined the pooled prevalence (PP) of patients positive for aPL in PAD or the PP of PAD in patients positive for aPL; we employed Peto's odds ratio with random effect for the meta-analysis. Results Twenty-one studies comprising 6,057 patients were evaluated: in patients with PAD, the PP of IgG aCL was 12% vs 4.1% in those without, IgM aCL was 13.2% vs 2.1%, and LA 13.3% vs 3.3%, respectively. The PP of patients with LA was greater in critical limb ischemia than in the control group (19.3% vs 4.2%). Also, the PP of patients with LA was greater in the failed than in the successful revascularisation group (35.8% vs 15.8%). The PP of post-procedural revascularisation failures was similar in the groups given or not given oral anticoagulation (59.2% vs 61.9%). Conclusion All the aPL related to PAD regardless of diagnostic definition used, whereas LA related also to critical limb ischaemia and failed revascularisation. Data expressed as percentage of participants positive for aPL limit the interpretation of these relationships.

Antiphospholipid (aPL) antibodies are more frequently detected among infertile women, but the association between aPL and in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes and whether need to get routine treatment are still controversial. The present study aims to find out whether infertile population with persistent aPL positive need treatment and which therapy is more effective. This retrospective study included 181 persistent aPL positive women, including 149 cases receiving anticoagulant treatment, either low-dose aspirin, low molecular weight heparin (LMWH) or aspirin plus LMWH adjuvant treatment (treated group), and 32 cases not receiving any treatment (untreated group). The treated group were further divided by combination therapy group (using both aspirin and LMWH，52 cases) and monotherapy group (only using aspirin，76 cases). The live birth rate and other clinical outcomes, including pregnancy rate, implantation rate, ongoing pregnancy rate and miscarriage rate were compared. The results show anticoagulant therapy can significantly improve live birth rate (59.06 % VS 34.48 %, P = 0.019), implantation rate (59.64 % VS 46.15 %, P＜0.001), ongoing pregnancy rate (59.73 % VS 34.38 %, P = 0.016), as well as reduce miscarriage rate (8.25 % VS 31.25 %, P＜0.001). Combination treatment of aspirin and LMWH exerts a higher live birth rate than monotherapy (75.00 % VS 53.95 %, P = 0.026). Infertile women with aPL positive might be classified as high-risk and low-risk aPL profiles. Those high-risk aPL positive infertile populations should be identified during IVF/ICSI and given corresponding thromboprophylaxis, and aspirin plus LMWH adjuvant treatment might be recommended.

Purpose: To evaluate the prevalence of a spectrum of autoantibodies in adult patients with non-infectious uveitis compared to healthy controls. Methods: This is a case-control study conducted in a tertiary referral center. Serum positivity to auto-antibodies directed at membranous phospholipids (aPL), nuclear antigens, and cytoplasmic (ANCA) antigens were assessed in sera from 63 non-infectious uveitis patients, and 78 healthy controls. Uveitis patients’ demographic and clinical data were collected retrospectively from their medical charts. Results: Of the spectrum of antibodies evaluated only aPL were linked with uveitis (OR 11.2, CI 1.4–92.1), as 13 (20.6%) uveitis patients were positive to at least one of the screened aPL, namely either anti-cardiolipin (aCL), anti-β2-glycoprotein (aβ2GPI), or anti-phosphatidylserine/prothrombin (aPS/PT). aCL antibodies were detected in 5/63 (7.9%) of uveitis patients and in none of controls ( p = 0.016). Positivity to either aCL or aβ2GPI was noted in 8/63 (12.7%) of uveitis patients and in 1 (1.3%) of the controls ( p = 0.011). Of the 13 uveitis patients positive to any of the aPL antibodies, 8 (62%) had exclusively anterior uveitis, 9 (69%) were idiopathic, and none had evidence of posterior vaso-occlusive involvement or systemic thrombotic manifestations. Conclusion: An association between aPL and uveitis among an unselected population of patients with no evidence of thrombosis or presence of the antiphospholipid syndrome was documented in this study. This link was observed, alike the general population of uveitis patients, mainly in patients with anterior eye inflammation. A possible interaction between aPL and uveitis, mediated by non-thrombotic mechanisms, requires further studies.

Background Small case-series have reported overt myocardial dysfunction to be associated with positive antiphospholipid antibodies in patients of systemic lupus erythematosus (SLE). However, there is no case-control study that has examined this association. Methods This case-control study recruited patients of SLE (fulfilling SLICC criteria) with overt myocardial dysfunction as cases and those without this as controls. Overt myocardial dysfunction was defined by echocardiography as global left ventricular dysfunction and reduced ejection fraction (Results This study included 51 patients (21 cases and 30 controls) having a mean (SD) age of 33 (13.3) years, and disease duration (median, IQR) of 28 months (12−38 months). The mean ejection fraction of cases was 31.7 (9.3)% while that of controls was 55.7 (1.7)% (p = 0.03). The frequency (percentage) of positive antiphospholipid antibodies was not significantly different between cases and controls (43%, 40%, p = 0.8). The frequency (percentage) of anti-cardiolipin antibody was also not significant between the groups (38%, 37%, p = 0.57). Serositis and leucopenia were more prevalent in SLE patients with myocardial dysfunction (p = 0.005). Conclusion This study did not find any significant association of anti-phospholipid antibodies with overt myocardial dysfunction in patients of SLE.

In the midst of the COVID-19 pandemic, further understanding of its complications points towards dysregulated immune response as a major component. Systemic lupus erythematosus (SLE) is also a disease of immune dysregulation leading to multisystem compromise. We present a case of new-onset SLE concomitantly with COVID-19 and development of antiphospholipid antibodies. An 18-year-old female that presented with hemodynamic collapse and respiratory failure, progressed to cardiac arrest, and had a pericardial tamponade drained. She then progressed to severe acute respiratory distress syndrome, severe ventricular dysfunction, and worsening renal function with proteinuria and hematuria. Further studies showed bilateral pleural effusions, positive antinuclear and antidouble-stranded DNA antibodies, lupus anticoagulant, and anticardiolipin B. C3 and C4 levels were low. SARS-Cov-2 PCR was positive after 2 negative tests. She also developed multiple deep venous thrombosis, in the setting of positive antiphospholipid antibodies and lupus anticoagulant. In terms of pathophysiology, COVID-19 is believed to cause a dysregulated cytokine response which could potentially be exacerbated by the shift in Th1 to Th2 response seen in SLE. Also, it is well documented that viral infections are an environmental factor that contributes to the development of autoimmunity; however, COVID-19 is a new entity, and it is not known if it could trigger autoimmune conditions. Additionally, it is possible that SARS-CoV-2, as it happens with other viruses, might lead to the formation of antiphospholipid antibodies, potentially contributing to the increased rates of thrombosis seen in COVID-19.

Background Anticardiolipin (aCL) and anti-β2 glycoprotein I (aβ2GPI) immunoglobulin A (IgA) antiphospholipid antibodies (aPL) have shown to associate with thrombosis and pregnancy morbidity. However, inclusion of IgA aPL in the classification criteria of the antiphospholipid syndrome (APS) has been debated. We investigated the value of aCL and aβ2GPI IgA aPL in the detection of thrombosis and pregnancy morbidity in addition to the current aPL panel for APS. Methods We included 1,068 patients from eight European medical centers: 259 thrombotic APS patients, 122 obstetric APS patients, 204 non-APS thrombosis patients, 33 non-APS obstetric patients, 60 APS patients with unspecified clinical manifestations, 196 patients with autoimmune diseases, and 194 controls. aCL and aβ2GPI IgG/M/A were detected with four commercial assays and lupus anticoagulant was determined by the local center. Results Positivity for IgA aPL was found in 17 to 26% of the patients with clinical manifestations of APS and in 6 to 13% of the control population. Both aCL and aβ2GPI IgA were significantly associated with thrombosis and pregnancy morbidity. Isolated IgA positivity was rare in patients with clinical manifestations of APS (0.3–5%) and not associated with thrombosis and/or pregnancy morbidity. Addition of IgA to the current criterion panel did not increase odds ratios for thrombosis nor pregnancy morbidity. Conclusion aCL and aβ2GPI IgA are associated with clinical manifestations of APS. However, isolated IgA positivity was rare and not associated with thrombosis or pregnancy morbidity. These data do not support testing for aCL and aβ2GPI IgA subsequent to conventional aPL assays in identifying patients with thrombosis or pregnancy morbidity.

Objectives aPL, the serum biomarkers of APS, are the most common acquired causes of pregnancy morbidity (PM). This study investigates the impact of aPL positivity fulfilling classification criteria (‘criteria aPL’) and at titres lower than thresholds considered by classification criteria (‘low-titre aPL’) on PM and assesses the effectiveness of low-dose aspirin (LDASA), low molecular weight heparin (LMWH) and HCQ in reducing the probability of PM (PPM). Methods Longitudinal data on 847 pregnancies in 155 women with persistent aPL at any titre and 226 women with autoimmune diseases and negative aPL were retrospectively collected. A generalized estimating equations model for repeated measures was applied to quantify PPM under different clinical situations. Results EUREKA is a novel algorithm that accurately predicts the risk of aPL-associated PM by considering aPL titres and profiles. aPL significantly impact PPM when at low titres and when fulfilling classification criteria. PPM was further stratified upon the aPL tests: aCL IgG/IgM and anti-β2-glycoprotein I (β2GPI) IgM, alone or combined, do not affect the basal risks of PPM, an increase occurs in case of positive LA or anti-β2GPI IgG. LDASA significantly affects PPM exclusively in women with low-titre aPL without anti-β2GPI IgG. The LDASA + LMWH combination significantly reduces PPM in all women with low-titre aPL and women with criteria aPL, except those carrying LA and anti-β2GPI IgG. In this group, the addition of HCQ further reduces PPM, although not significantly. Conclusion EUREKA allows a tailored therapeutic approach, impacting everyday clinical management of aPL-positive pregnant women.

Direct oral anticoagulants have become the mainstay of the management of venous thromboembolism and atrial fibrillation, and long-term anticoagulation is indicated for those at high risk of further thrombotic events. This includes patients diagnosed with antiphospholipid syndrome, for whom the ‘triple positive’ laboratory combination of lupus anticoagulant, β2-glycoprotein-1 and anti-cardiolipin antibodies signify those at greatest risk. Data from meta-analysis and randomised control trials have raised the concern that direct oral anticoagulants may be less effective than vitamin K antagonists for the prevention of thrombosis in patients with thrombotic antiphospholipid syndrome, particularly those with the triple positive profile. This article reviews the diagnosis of thrombotic antiphospholipid syndrome, strategies for testing without interruption of anticoagulation, evidence concerning the safety of direct oral anticoagulants in this setting, and the implications for current investigation and management of unprovoked venous thromboembolism.

Background The concurrent presence of lupus anticoagulant, anticardiolipin, and anti β2-glycoprotein I antibodies (triple positive profile) identifies patients at high risk of thromboembolic events. These patients are also positive for anti-phosphatidyl-serine/prothrombin antibodies (tetra-positive profile). Objective Understand which antibody among anti-β2-glycoprotein I and anti-phosphatidyl-serine/prothrombin is responsible for lupus anticoagulant activity. Patients/methods Affinity purified anti-β2-glycoprotein I antibodies from plasma of 14 tetra-positive patients spiked into normal pooled plasma were tested. Results and conclusions Anti-β2-glycoprotein I antibodies did not prolong the diluted Russell viper venom time and silica clotting time (median ratio 0.98, interquartile ratio [IQR] 0.9-1.06; and 1.0, IQR 0.91-1.03, respectively). Anticoagulant activity remained in the flow-through that was deprived of anti-β2 glycoprotein I antibodies (median ratio 1.88, IQR 1.58-2.77; and 1.75, IQR 1.17-2.9, respectively). This material was loaded on size-exclusion chromatography Sephacryl S-300 column and showed that anticoagulant activity and anti-phosphatidyl-serine/prothrombin antibodies coeluted in the same fractions. Besides, the flow through was poured into a prothrombin affinity column. Protein yield in three patients ranged from 54 to 91 μg/mL and showed strong positivity in phosphatidyl-serine/prothrombin ELISA. The affinity purified material prolonged the coagulation time of normal pooled plasma: the diluted Russell viper venom ratio in the three patients was 2.09, 1.21, and 1.35; that of silica clotting time was 2.05, 1.5, and 2.13. In conclusion, under the assay conditions used, anticoagulant activity in tetra-positive antiphospholipid syndrome patients may largely be attributable to anti-phosphatidyl-serine/prothrombin antibodies.

Background Classification of the antiphospholipid syndrome (APS) relies predominantly on detecting antiphospholipid antibodies (aPLs). Antibodies against a domain I (DI) epitope of anti-beta 2glycoprotein I (beta 2GPI) proved to be pathogenic, but are not included in the current classification criteria. Objectives Investigate the clinical value of detecting anti-DI IgG in APS. Patients/Methods From eight European centers 1005 patients were enrolled. Anti-cardiolipin (CL) and anti-beta 2GPI were detected by four commercially available solid phase assays; anti-DI IgG by the QUANTA Flash (R) beta 2GPI domain I assay. Results Odds ratios (ORs) of anti-DI IgG for thrombosis and pregnancy morbidity proved to be higher than those of the conventional assays. Upon restriction to patients positive for anti-beta 2GPI IgG, anti-DI IgG positivity still resulted in significant ORs. When anti-DI IgG was added to the criteria aPLs or used as a substitute for anti-beta 2GPI IgG/anti-CL IgG, ORs for clinical symptoms hardly improved. Upon removing anti-DI positive patients, lupus anticoagulant remained significantly correlated with clinical complications. Anti-DI IgG are mainly present in high-risk triple positive patients, showing higher levels. Combined anti-DI and triple positivity confers a higher risk for clinical symptoms compared to only triple positivity. Conclusions Detection of anti-DI IgG resulted in higher ORs for clinical manifestations than the current APS classification criteria. Regardless of the platform used to detect anti-beta 2GPI/anti-CL, addition of anti-DI IgG measured by QUANTA Flash (R) did not improve the clinical associations, possibly due to reduced exposure of the pathogenic epitope of DI. Our results demonstrate that anti-DI IgG potentially helps in identifying high-risk patients.

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.

Background The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with the persistent presence of lupus anticoagulant (LAC), anti-cardiolipin (aCL) and/or anti-beta 2glycoprotein I (a beta 2GPI) antibodies of the immunoglobulin G/immunoglobulin M (IgG/IgM) isotype. However, the role of aCL and a beta 2GPI IgM as a serologic marker in APS is debated. Objectives We aimed to assess the diagnostic and clinical value of IgM antiphospholipid antibodies (aPL) in APS within the classification criteria. Patients/Methods Our multicenter study comprised 1008 patients, including APS patients and controls. Anti-CL and a beta 2GPI IgG and IgM antibodies were detected with four commercially available solid phase assays. Results Positivity for aCL and/or a beta 2GPI antibodies was significantly correlated with thrombosis and pregnancy morbidity, independent of the isotype and solid phase assay. Higher odds ratios were obtained for IgG compared to IgM positivity. Isolated IgM was rare in thrombotic APS, but more frequent in obstetric APS, ranging from 3.5% to 5.4% and 5.7% to 12.3%, respectively, dependent on the solid phase assay. In a multivariate logistic regression analysis of aPL, IgM positivity was found to be associated with pregnancy morbidity. However, detection of IgM was not independently associated with thrombosis. Combined positivity for LAC, IgG, and IgM was highly associated with thrombosis and pregnancy morbidity. Conclusions Our data support testing for aCL and a beta 2GPI IgM in women suspected of obstetric APS. However, no added value was found for testing IgM in patients suspected of thrombotic APS. Still, IgM aPL might be useful as a second-line test to improve thrombotic risk stratification.

One of the main groups of lipids is phospholipids, which are mainly involved in forming cell membranes. Neoplastic processes such as cell replication have increased lipid synthesis, making tumor cells dependent on this synthesis to maintain their requirements. Antiphospholipid antibodies attack phospholipids in the cell membranes. Three main types of antiphospholipid antibodies are recognized: anti-β2 glycoprotein I (anti-β2GP-I), anticardiolipin (aCL), and lupus anticoagulant (LA). These types of antibodies have been proven to be present in hematological neoplasms, particularly in LH and NHL. This review on antiphospholipid antibodies in hematological neoplasms describes their clinical relationship as future implications at the prognostic level for survival and even treatment.

BACKGROUND: Anticardiolipin antibodies (aCL) and anti‐β(2)‐glycoprotein I antibodies (aβ(2)GPI) are essential in diagnosing antiphospholipid syndrome (APS) according to the international APS guideline. Five commercial assays for aCL and aβ(2)GPI are available in Japan, but their test results are quite discordant. For harmonization of diagnosing APS, upper reference limit (URL) and diagnostic accuracy of each assay were evaluated and compared by testing common sets of specimens across all assays. METHODS: We evaluated two manual and three automated assays for aCL and aβ(2)GPI of IgG‐ and IgM classes. 99%URL (the upper limit of reference interval: as per guideline) together with 97.5%URL were determined by testing sera from 198 to 400 well‐defined healthy subjects. Both URLs were compared with the cutoff values, which were determined based on ROC analysis by testing 50 each of plasma specimens from patients with/without APS. Diagnostic accuracy was evaluated as area under curve (AUC) of the ROC curve. RESULTS: A variable degree of discrepancy between URLs and the cutoff values was observed, which was partly attributable to between‐year assay variability. 97.5%URLs were set lower and closer to the cutoff values than 99%URLs. For all assays, diagnostic accuracies of both aβ(2)GPI‐IgG and aCL‐IgG were generally high (AUC: 0.84−0.93); whereas those for IgM‐class assays were low (AUC: 0.57−0.67), implicating its utility is limited to rare IgG negative APS cases. CONCLUSION: To ensure harmonized APS diagnosis, the diagnostic thresholds of the five assays were evaluated by common procedures. Contrary to the guideline, 97.5%URL is rather recommended for diagnosing APS, which showed a closer match to the cutoff value.

Introduction: Increased antiphospholipid antibodies (aPL) have been described in human immunodeficiency virus (HIV) infection. However, the association between aPL and the increased risk of thrombosis in HIV requires further clarification. Methods: We reviewed the medical records of 215 consecutive women with a history of thrombosis and/or obstetric complications (158 HIV-uninfected and 57 HIV-infected) between July 2017 and March 2021. Participants (n = 215) without clinical criteria manifestations for antiphospholipid syndrome were included as matched controls. Testing for lupus anticoagulant (LAC), anticardiolipin (aCL) and anti-beta2-glycoprotein1 (aβ2GP1) IgM and IgG was performed. Results: Thirty-two (10.1%) HIV-uninfected and 15 (13.2%) HIV-infected participants were positive at baseline for one of the five criteria aPL, with no statistically significant difference. The profile of the HIV-infected participants with thrombosis (n = 11) included LAC in 15.8%, aCL IgG in 3.5% and aβ2GP1 IgG in 1.8%. In contrast, the HIV-infected controls (n = 4), included aCL IgM in 1.8% and aβ2GP1 IgM in 5.3%. Only LAC was significantly associated with thrombosis (p

Background. The detection of antiphospholipid antibodies (aPL) is of interest because of their importance in the pathogenesis of arterial or venous thrombosis. They could be a “second hit” of an inflammatory event such as infection. The aim of our study was to assess the performance of antiphospholipid antibody biomarker to predict in-hospital mortality in intensive care unit (ICU) septic patients. Methods. We conducted a prospective single-center observational study including consecutive critically ill septic adults admitted to the intensive care unit. Clinical and laboratory data including enzyme-linked immunosorbent assay for antiphospholipid antibodies (anticardiolipin (aCL), antiphosphatidylserine (aPS)) were obtained. Blood samples were collected on days 1, 3, 5, 8, and 10 of hospitalization. The primary study endpoint was ICU mortality defined as death before ICU discharge. Secondary end points included correlation between SOFA score and biological parameters. Results. A total of 53 patients were enrolled. 18.8% of patients were aPL positive. In-hospital mortality rate was 60%. Multivariate analysis showed that age and aCL at days 3 and 5 along with SOFA at day 3 were independent outcome predictors. A significant positive correlation existed between SOFA at days 3, 5, and 8 and antiphospholipid antibody concentrations. Conclusions. Our data showed that antiphospholipid was useful biomarkers for the prediction of mortality in critically ill septic patients. We found a positive correlation between SOFA score and antiphospholipid antibodies.

ObjectivesTo describe the outcomes of pregnancies in antiphospholipid antibody (aPL)-positive patients since the inception of the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Registry.MethodsWe identified persistently aPL-positive patients recorded as ‘pregnant’ during prospective follow-up, and defined ‘aPL-related outcome’ as a composite of: (1) Preterm live delivery (PTLD) at or before 37th week due to pre-eclampsia (PEC), eclampsia, small-for-gestational age (SGA) and/or placental insufficiency (PI); or (2) Otherwise unexplained fetal death after the 10th week of gestation. The primary objective was to describe the characteristics of patients with and without aPL-related composite outcomes based on their first observed pregnancies following registry recruitment.ResultsOf the 55 first pregnancies observed after registry recruitment among nulliparous and multiparous participants, 15 (27%) resulted in early pregnancy loss ConclusionIn our multicentre, international, aPL-positive cohort, of 55 first pregnancies observed prospectively, 15 (27%) were complicated by early pregnancy loss. Of the remaining 40 pregnancies, composite pregnancy morbidity was observed in 9 (23%) pregnancies.

Antiphospholipid antibodies (aPL) comprise a panel of autoantibodies that reflect a potential prothrombotic risk in several autoimmune conditions, most notably antiphospholipid (antibody) syndrome (APS). aPL can be divided into those that form part of the laboratory criteria for APS, namely, lupus anticoagulant (LA), as well as anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (aβ2GPI) of the immunoglobulin G and M classes, and those that form a group considered as “noncriteria antibodies.” The noncriteria antibodies include, for example, antiphosphatidylserine antibodies (aPS), antiprothrombin antibodies (aPT), and antiphosphatidylserine/prothrombin complex antibodies (aPS/PT). COVID-19 (coronavirus disease 2019) represents a prothrombotic disorder, and there have been several reports of various aPL being present in COVID-19 patients. There have also been similarities drawn between some of the pathophysiological features of COVID-19 and APS, in particular, the most severe form, catastrophic APS (CAPS). In this review, we critically appraise the literature on aPL and COVID-19. This is a companion piece to a separate review focused on LA. In the current review, we primarily concentrate on the so-called solid phase identifiable aPL, such as aCL and aβ2GPI, but also reflect on noncriteria aPL. We conclude that aPL positivity may be a feature of COVID-19, at least in some patients, but in general, identified “solid-phase” aPL are of low titer and not able to be well-linked to the thrombotic aspects of COVID-19. Also, most publications did not assess for aPL persistence, and where persistence was checked, the findings appeared to represent transient aPL. Importantly, high-titer aPL or multiple aPL positivity (including double, triple) were in the minority of COVID-19 presentations, and thus discount any widespread presence of APS, including the most severe form CAPS, in COVID-19 patients.

Objectives To identify the aggregation of patients with aPL into different subgroups sharing common features in terms of clinical and laboratory phenotypes. Methods We applied a hierarchical cluster analysis from the multiple correspondence analysis to determine subgroups of patients according to clinical and laboratory characteristics in a cohort of subjects with confirmed aPL positivity who presented to our outpatient clinics from 2006 to 2018. Results A total of 486 patients [403 women; age 41.7 years (26)] were included, resulting in five clusters. Cluster 1 (n= 150) presented with thrombotic events (65.3% with venous thrombosis), with triple aPL positivity found in 34.7% of them (the highest rate among the different clusters). All the patients from cluster 2 (n = 91) had a confirmed diagnosis of SLE and the highest rate of anti-dsDNA positivity (91.7%). Cluster 3 included 79 women with pregnancy morbidity. Triple positivity was present in 3.8%, significantly lower when compared with Cluster 1 (34.7% versus 3.8%, P Conclusion While clusters 1, 2, 3 and 5 corresponded to well-known entities, cluster 4 might represent a bridging condition between pure primary APS and defined SLE, with lower thrombotic risk when compared with primary APS but higher general features such as ANA and cytopenia (mainly thrombocytopenia).

Introduction Antiphospholipid syndrome is a chronic autoimmune disease with a high prevalence in females. Published data have identified that antiphospholipid antibodies (APLA) of antiphospholipid syndrome are risk factors for poor pregnancy outcomes, such as recurrent spontaneous abortion, intrauterine growth restriction and preeclampsia. However, the association between APLA and late fetal loss is not fully understood and remains controversial. The aim of this study is to identify and analyze the recent publications to better understand the association between APLA and late fetal loss. Material and methods The literature was searched on 31 January 2019 using Ovid, Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) to evaluate the association between APLA and late fetal loss, with articles published before January 2019, according to the PRISMA statement. Without imposing regional restrictions, referenced articles were selected. Quality assessment was conducted independently by two reviewers, based on the Newcastle-Ottawa scale. For the meta-analysis, we used odds ratios (random effects model). The between-study heterogeneity was assessed by Q test. Publication bias was assessed by funnel plots. Results Nineteen studies (with 10 265 cases) were included in the final analysis. The odds ratio (OR) for the late fetal loss with lupus anticoagulant was 5.02 (95% confidence interval [CI] 2.14-7.89). Seven included studies reported that lupus anticoagulant had a statistically significant association with late fetal loss. The results did not show a statistically significant association between anticardiolipin antibodies and late fetal loss. The pooled odds ratio for the association of anticardiolipin antibodies with late fetal loss was 3.47 (95% CI 0.68-6.26). However, we did find the relation between anticardiolipin antibodies and late fetal loss among cohort studies (OR 2.27, 95% CI 1.20-3.44). Anti-beta2 glycoprotein 1 antibodies (β2GP1) showed a significant association with late fetal loss (OR 3.13, 95% CI 0.75-5.50). Conclusions Lupus anticoagulant is strongly associated with late fetal loss in antiphospholipid syndrome patients. However, the association between anticardiolipin antibodies and late fetal loss is inconsistent. There are currently insufficient data to support a significant relation between β2GP1 and late fetal loss.

To compare clinical and laboratory data obtained from patients with primary Antiphospholipid Syndrome (pAPS) with and without Thrombotic Microangiopathy (TMA).A cross-sectional study with 66 (83.3% female) pAPS patients was performed. Demographic, clinical, drug use, antiphospholipid antibodies data were evaluated. Patients were subdivided into one of two groups: pAPS with TMA and pAPS without TMA and were compared.In this sample, 5/66 (7.6%) of patients had TMA. Primary APS with TMA group exhibited a higher frequency of arterial events (100% vs. 54.1%, p=0.02), stroke (100% vs. 32.8%, p=0.001) and a lower frequency of deep venous thrombosis (0 vs. 68.9%, p=0.0009) compared to the patients without TMA. Analysis of therapy used in these patients showed a higher frequency of current (40% vs. 6.6%, p=0.0006) and previous glucocorticoid use (80% vs. 36%, p=0.0007) and statin use (50% vs. 22.9%, p=0.037) in the first group. The two groups exhibited no differences in the frequency of positive autoantibodies, except for higher IgG anticardiolipin titers (86 ± 52 vs. 34.5 ± 39 GPL, p=0.003).Patients with pAPS and TMA have distinct clinical and laboratory spectra from those without TMA, that is characterized by an increased frequency of arterial events, stroke, and higher titers of IgG anticardiolipin; they have deep venous thrombosis less frequently.

This study aimed to implement lupus anticoagulant (LAC) detection techniques according to the International Society on Thrombosis and Hemostasis (ISTH) recommendations, in the Biological Laboratory of the Maternity and Neonatal Medicine Center (Monastir, Tunisia) and to evaluate the profile and the prevalence of antiphospholipid antibodies (aPL) in the obstetric antiphospholipid syndrome (OAPS).We collected two groups: a "case group" (53 women who presented one or more obstetrical criteria of APS) and a "control group." LAC was detected following the four steps recommended by ISTH 2009. Anticardiolipin (aCL) and antibeta-2-glycoprotein I (aβ2GPI) antibodies testing were performed by enzyme-linked immunosorbent assay (ELISA).aPL were found in five patients: three patients with isolated LAC, one patient with isolated IgG aCL, and one patient with triple positivity (LAC, aCL IgM, aβ2GPI IgM). Concerning LAC, 13 (24.52%) of 53 patients had a screening step with at least one positive test. The mixing step was positive in four patients and then confirmed in the confirmatory test. Thus, the prevalence of LAC in our study group is 7.54%. Surprisingly, among these positive patients, one patient had an associated combined factor V (FV) and factor VIII (FVIII) deficiency.There is no single test and no algorithm that can detect all types of LAC. It seems that the recent 2020 ISTH algorithm allows a better detection of low activity LAC than the 2009 algorithm. In our study, the most frequently identified antiphospholipid antibodies were LAC more than aCL and aβ2GPI.

Anti‑β

Patients with autoimmune diseases (ADs) are a challenge for the intensivist; it is hard to differentiate among infection, disease activity, and combinations of both, leading to high mortality. This study is a retrospective analysis of 124 critically ill patients admitted to the intensive care unit (ICU) in a university hospital between 2008 and 2016. Bivariate case-control analysis was performed, using patients who died as cases; later, analysis using a logistic regression model with variables that were associated with mortality was conducted. Four variables were consistently associated with mortality in the logistic regression model and had adequate prediction value (Hosmer and Lemeshow statistic = 0.760; Nagelkerke R-squared = 0.494). The risk of death was found to be statistically associated with the following: shock at admission to ICU [odds ratio (OR): 7.56; 95% confidence interval (CI): 1.78-31.97, p = 0.006], hemoglobin level

Objective. Antiphospholipid syndrome (APS) is a chronic autoimmune disease with a high prevalence in females. Published data have identified pregnant women with APS may suffer from recurrent miscarriage, fetal death. However, the association between antiphospholipid antibody (aPL) and fetal growth restriction (FGR) remains controversial. This study aims to systematically review the literature on population-based studies investigating an association between aPL and FGR. Methods. The literature was searched on 1 November, 2021, using Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL), following the MOOSE checklist. Study inclusion criteria focused on peer-reviewed published articles that reported an association between aPL and FGR. Quality assessment was performed based on the Newcastle-Ottawa scale. The between-study heterogeneity was assessed by the Q test. Publication bias was assessed by funnel plots. Results. Twenty-two studies (with 11745 pregnant women) were included in the final analysis. Pooled odds ratio for association of aPL, anticardiolipin antibodies (ACA), anti-beta2 glycoprotein 1 antibodies (β2GP1), and FGR was 1.26 (95%CI 1.12, 1.40), 2.25 (95%CI 1.55, 2.94), and 1.31 (95% CI 1.12, 1.49), respectively. Lupus anticoagulant (LA) did not increase the chance of FGR (OR 0.82, 95%CI 0.54, 1.10). Conclusions. Our meta-analysis showed that aPL increased the risk of FGR. The risk of FGR varies with the aPL types. ACA and β2GP1 are strongly associated with FGR. There are currently insufficient data to support a significant relationship between LA and FGR.

Antiphospholipid syndrome (APS) is an uncommon autoantibody-mediated condition characterised by acquired thrombophilia resulting in recurrent arterial and venous thrombosis. An inciting factor allows for the exposure of endothelial phospholipids, causing antigen formation and subsequent creation of antibodies. A woman in her 70s presented after vehicular trauma, suffering broken ribs, pneumothorax and incidentally discovered left adrenal haemorrhage. Two weeks later she presented with acute-onset abdominal pain and was found to have a right adrenal gland haemorrhage on CT imaging without interval trauma occurring. The patient had antiphospholipid antibody laboratory studies drawn and was given intravenous heparin with a bridge to warfarin at discharge. Laboratory results returned positive for lupus anticoagulant, beta-2 glycoprotein and anticardiolipin antibodies indicating triple positivity, with repeated laboratory tests positive in 12 weeks’ time, confirming the diagnosis. Bilateral adrenal haemorrhage, rather than traditional venous thromboembolism, was the presenting pathology in this patient’s diagnosis of APS.

Background This study aimed to analyze the abnormal rates of immune related factors in serum of sudden deafness (SD) patients, and to discuss the correlation between these indicators and the degree of pathological changes of SD patients. Methods From March 2018 to January 2021, 90 patients with SD who were hospitalized in Beijing Tsinghua Changgeng Hospital were enrolled as participants, and 60 healthy examinees served as the control group. Antinuclear antibody (ANA), anticardiolipin antibody immunoglobulin G (ACA-IgG), anticardiolipin antibody immunoglobulin M (ACA-IgM), and anti-β-glucoprotein (anti-β-GP) antibody were detected by enzyme-linked immunosorbent assay (ELISA). Results In the SD group, 43 participants were positive for ANA, while in the control group, only 9 participants were positive for ANA. The titer of antibodies was significantly higher in the SD group than in the control group. The differences in abnormal rates of ACA-IgG, ACA-IgM, and anti-β-GP antibodies between the SD group and control group were not statistically significant (P>0.05). Conclusions The pathogenesis of SD is correlated with autoimmune factors to a certain extent. In the course of clinical treatment, in addition to vasodilation, neurotrophic therapy, and thrombolytic therapy, patients can also be approached from the perspective of autoimmunity, which may achieve more ideal treatment effects.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder caused by the presence of aPLs (antiphospholipid antibodies, i.e., anti-β2-glycoprotein I and anti-cardiolipin). Everyday practice in terms of laboratory diagnostics of APS includes determination of aPLs and well-known functional assays assessing for lupus anticoagulant (LA), in turn using various tests. According to recent guidelines, the recommended method for LA identification or exclusion is based on the Russell Viper Venom test and a sensitive activated partial thromboplastin time assay. Despite the fact that LA can be quantified in laboratory practice in this way, LA is still used as a binary parameter that is just one of the risk factors of thrombosis in APS. As of today, there are no other functional assays to routinely assess the risk of thrombosis in APS. It is well-known that APS patients display a wide range of clinical outcomes although they may express very similar laboratory findings. One way to solve this dilemma, could be if antibodies could be further delineated using more advanced functional tests. Therefore, we review the diagnostic approaches to test the function of aPLs. We further discuss how thrombin generation assays, and rotational thromboelastometry tests can be influenced by LA, and how experimental methods, such as flow cytometric platelet activation, surface plasmon resonance, or nano differential scanning fluorimetry can bring us closer to the puzzling interaction of aPLs with platelets as well as with their soluble protein ligand. These novel approaches may eventually enable better characterization of aPL, and also provide a better linkage to APS pathophysiology.

BackgroundDiagnosis of antiphospholipid syndrome (APS) is based on the positivity of laboratory criteria antiphospholipid antibodies (aPLs). Test results for aPLs could be contradictory among different detection methods as well as commercial manufacturers. This study aimed to assess and compare the diagnostic and analytic performances of four commercial assays prevalently used in China.MethodsA total of 313 patients including 100 patients diagnosed with primary APS, 52 with APS secondary to SLE, 71 with SLE, and 90 health controls were recruited. Serum IgG, IgM, and IgA for aCL, and aβ2GPI antibodies were detected with two ELISA and two CLIA systems, and test system with the best diagnostic value was explored of its correlation with key clinical features.ResultsCLIA by YHLO Biotech Co. was considered as the system with the best predictive power, where 58.55 and 57.89% of APS patients were positive for aCL or aβ2GPI for at least one antibody (IgG or IgM or IgA). Overall, CLIA showed better performance characteristics than traditional ELISA test systems.ConclusionCLIA was considered as a better platform for aPL detection in APS diagnosis. A combination of other detection platforms could assist in differential diagnosis as well as in identifying high-risk patients.