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ObjectiveOsteonecrosis (ON), which can lead to physical disability, is a common complication of systemic lupus erythematosus (SLE). The purpose of this study was to determine the prevalence of ON and identify possible risk factors in Chinese SLE patients.MethodsSLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were recruited from the Peking Union Medical College Hospital. The chi-square test (χ2test) and multivariate regression analyses were used to evaluate risk factors. The Cox proportional-hazards model was used to construct the survival curves and estimate the simultaneous effects of prognostic factors on survival.ResultsWe consecutively enrolled 1,158 patients, of which 88 patients (7.6%) developed ON. Among ON patients, 57.1% of patients had isolated femoral head necrosis and 42.9% had multiple joint involvement. The mean age of ON patients (24.62 ± 8.89 years) was significantly younger than SLE patients without ON (27.23 ± 10.16 years, p = 0.09). The ON group presented with a much longer disease course (10.68 ± 5.97 years, p ConclusionsON remains a serious and irreversible complication in SLE. In addition to glucocorticoid therapy, we found that CNS system involvement was a risk factor for ON, while the administration of hydroxychloroquine was a protective factor. The clinical characteristics of multiple site ON patients were distinct from isolated femoral head necrosis patients. The presence of aPLs was a risk factor for multiple site osteonecrosis.

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.

To identify predictors of systemic lupus erythematosus (SLE) flares during pregnancy in patients previously considered to be at low risk.The retrospective cohort study included 54 singleton pregnancies, managed between 2005 and 2019, involving maternal diagnosed SLE at a low disease activity (SLE Disease Activity Index ≤4) for ≥12 months before conception and without anti-phospholipid antibodies. Pregnancy outcomes were compared between patients who had SLE exacerbations during pregnancy (flare group,The flare group had shorter gestational durations (A prednisone dose ≥10.5 mg daily and CH50 hypocomplementemia in early pregnancy are useful in the early detection of patients at a high risk of SLE exacerbation.

Purpose: The aim of our study was to evaluate the prevalence of aPLAs among Tunisian critically-ill covid19 and non-covid19 patients and to investigate the clinical significance of aPLAs by determining the SOFA score and their respiratory failure during their ICU stay. Methods: We conducted a prospective observational cohort study including critically ill COVID-19 patients and non-COVID-19 patients with pulmonary origin sepsis, admitted to the intensive care unit. Blood samples were collected on days 1, 3, 5, 8 and 10 of hospitalization in order to measure titers of anti-cardiolipin (aCL), anti-phosphatidylserine (aPS) by chemiluminescence immunoassay. Results: We enrolled 43 COVID-19 patients and 31 non COVID-19 with pulmonary origin sepsis. In-hospital mortality rate was significantly higher (p=0.026) in COVID-19 patients (79%). 58.8% of COVID-19 patients were aPLA positive; however, only 22.5% of the non-COVID-19 were positive for aPLA (p=0.002). A significant positive correlation existed between respiratory SOFA component at days 3, 5, 8 and 10 and anti-phospholipid antibodies concentrations. Conclusion: Based on our results, for the first time, anti-phospholipid antibodies may be used as an independent indicator of respiratory organ failure in critically ill patients, to stratify and assess the prognosis of pulmonary origin sepsis and COVID-19.

Background: COVID-19 clinical features include a hypercoagulable state that resembles the antiphospholipid syndrome (APS), a disease characterized by thrombosis and presence of antiphospholipid antibodies (aPL). The relationship between aPL-presence and the appearance of thrombi as well as the transience or permanence of aPL in COVID-19 patients is not sufficiently clear. Methods: A group of 360 COVID-19 patients were followed-up for 6 months. Classic aPL, anti-B2GPI IgA, anti-phosphatidylserine/prothrombin IgG/M and anti-SARS-CoV-2 antibodies were determined at acute phase and &gt, 12 weeks later. The reference group included 143 healthy volunteers of the same age-range distribution. Results: aPL prevalence was similar in COVID-19 patients and the reference population. aPL presence in both determinations was significantly associated with thrombosis (OR: 2.33 and 3.71), strong agreement being found for classic aPL and anti-B2GPI IgA (Weighted kappa: 0.85–0.91). Thrombosis-associated aPL occurred a median of 17 days after hospital admission (IQR: 6–28) vs. 4 days for the rest (IQR: 3–7). Although anti-SARS-CoV-2 antibodies levels increased during convalescence, aPL hardly changed. Conclusions: Most COVID-19 patients would carry these aPL before the infection. At least two mechanisms could be behind thrombosis, early immune-dysregulation-mediated thrombosis after infection and belated-aPL-mediated thrombosis, with SARS-CoV-2 behaving as a second hit.

ZusammenfassungDas Antiphospholipid-Syndrom ist eine der schwerwiegendsten thrombophilen Störungen, die nicht nur zu rezidivierenden venösen, sondern auch zu arteriellen Thromboembolien sowie Schwangerschaftskomplikationen führen kann. Zusammen mit dem klinischen Bild ist das APS durch spezifische Laborbefunde charakterisiert: 1. Lupus Antikoagulans (LA), 2. Anticardiolipin-Antikörper (ACA), 3. β2-Glykoprotein I-Antikörper (β2GPI-AK). Alle Testergebnisse müssen nach 12 Wochen bestätigt werden. Sind alle drei Testgruppen positiv, besteht das höchste thrombotische Risiko. Beachtet werden muss, dass LA-Tests unter UFH, VKA oder DOAKs falsch positiv ausfallen können; bei DOAKs scheint die Zugabe von Absorbern nach Blutentnahme zuverlässige Ergebnisse zu liefern.Eine Vergleichsstudie (TRAPS) zwischen VKA und dem DOAK Rivaroxaban mit ausschliesslich 3-fach positiven Hochrisiko-Patienten wurde vorzeitig abgebrochen, wegen erhöhter Ereignisraten unter Rivaroxaban [19 % zumeist arterielle Ereignisse versus 3 % unter Warfarin (HR 7.4; 1.7–32.9)]. Ein daraufhin herausgegebener Rote-Hand-Brief warnt vor der Anwendung von DOAKs bei Patienten mit APS, insbesondere bei Hoch-Risiko- (3-fach positiven) Patienten, und empfiehlt die Überprüfung einer laufenden DOAK-Therapie und eine mögliche Umstellung auf VKA, insbesondere bei Hoch-Risiko-Patienten. Als Fazit soll 1. bei klinischem Verdacht eine sorgfältige APS-Diagnostik erfolgen. Viele Patienten haben aufgrund von inadäquater Diagnostik wahrscheinlich gar kein APS und können bei venöser Thromboembolie adäquat ein DOAK erhalten.2. Bei einfach- oder zweifach-positiven Antiphospholipid-AK Tests ohne LA besteht ein vergleichbar niedriges Thromboserisiko; auch hier kann möglicherweise ebenfalls mit DOAKs behandelt werden, wenn venöse Thrombosen vorliegen – ausreichende Daten liegen noch nicht vor, aber Metaanalysen legen dies nahe. 3. Patienten mit Positivität in allen 3 APS-Tests und APS-Patienten mit arteriellen Thromboembolien haben ein sehr hohes Risiko. Die TRAPS-Studie zeigt, dass diese Patienten nicht mit DOAKs, sondern mit einem VKA behandelt werden sollen.

We report two cases of coronavirus disease 2019 (COVID-19) in patients who developed pulmonary embolism and transient anti-phospholipid antibodies. At the time of presentation with acute pulmonary embolism, both patients had leukocytosis and increased levels of anti-cardiolipin antibodies, which resolved at testing 12 weeks after initial presentation. Studying cases of pulmonary embolism and increased anti-phospholipid antibodies in the context of COVID-19 could be one of the factors for elucidating the possible connection between severe acute respiratory syndrome coronavirus 2 infection, anti-phospholipid antibodies, and thrombosis.

Anti-phospholipid syndrome (APS) recapitulates the link between autoimmunity and pregnancy failure: Acquired anti-phospholipid antibodies (aPL) play a pathogenic role in pregnancy complications. The diagnosis of obstetric APS can easily be pursued when women present with laboratory and clinical features fulfilling the international classification criteria. Standard therapeutic approach to obstetric APS consists in the association of anti-platelet agents and anticoagulants. Most patients achieve a live birth thanks to conventional treatment; however, approximately 20% fail to respond and are managed with additional therapeutic tools added on the top of conventional treatment. Surely, a refinement of risk stratification tools would allow early identification of high-risk pregnancies that warrant tailored treatment. In real life, obstetricians and rheumatologists face complex diagnostic scenarios including women with pregnancy morbidities other than those mentioned in classification criteria such as one or two early losses and premature birth after 34 weeks due to preeclampsia or placental insufficiency, women with low-titer aPL not fulfilling criteria laboratory requirements, women with positive non-criteria aPL, asymptomatic aPL carriers, and infertile women found to be aPL-positive. This review focuses on some of the several unanswered questions related to diagnostic, prognostic, and therapeutic aspects in obstetric APS.

Apart from occlusions involving a large variety of venous and arterial vessels, antiphospholipid antibodies (aPL) have been associated less frequently with a number of other clinical manifestations. Some of these complications are more often associated with aPL antibodies (e.g., chorea, livedo reticularis) while others occur less frequently. Clearly, thrombotic occlusions may be the underlying pathogenetic mechanism operating in some, but other factors, as yet unidentified, may be responsible in conditions such as chorea or pulmonary hypertension. Skin lesions occurring in association with aPL antibodies may comprise a variety of cutaneous and subcutaneous manifestations similar to vascular occlusions seen in vessels to other organs. Livedo reticularis, a cyanotic, geographically distributed “network” pattern of dilated superficial veins, often precipitated or aggravated by cold, may occur in normal children and adults.

Whereas some previous data on carriers with isolated antiphospholipid antibodies positivity (APP) suggested an increased risk of arterial events in this clinical setting, no data are available on subclinical atherosclerosis in this clinical setting. This article reports data on intima-media thickness of the common carotid artery (CCA-IMT) and of the Bulb (Bulb-IMT) and on the prevalence of carotid plaques in APP carriers and in subjects with antiphospholipid syndrome (APS) specifically stratifying for the presence of thrombotic manifestations, cardiovascular risk factors, antibody isotype and concomitant Systemic Lupus Erythematosus (SLE) or other autoimmune diseases.

The aim was to study the feto-maternal outcome of pregnancies complicated by systemic lupus erythematosus (SLE). Analysis of a prospectively-maintained database of 73 patients (June 2006-March 2016) was done. Diagnosis of SLE was made by ACR(American College of Rheumatology)-criteria. Protocol scans and blood tests were done and patients with active disease were followed biweekly for 28 weeks, and weekly thereafter. Mean age + SD was 29 ± 4.9. SLE was diagnosed before conception in 86% of patients. A total of 33% had active disease status during pregnancy and out of them 58% had a flare of SLE, compared to 26% who were in remission (p = .008). SLE activity had no effect on the rate of foetal demise (p = .57). Overall pregnancy loss was 14% with no maternal mortality. The incidence of SLE flare during pregnancy was significantly higher in patients who had active disease. But the incidence of foetal demise was not affected by disease activity. Impact Statement What is already known on this subject: SLE is one of the most common immunological disorders associated with pregnancy. Both SLE and pregnancy tend to influence each other due to complex interaction. The opinion seems to be divided regarding influence of pregnancy on SLE flare in world literature. What the results of this study add: Our data suggests a significantly greater incidence of SLE flare during pregnancy in patients with active disease, than in those in remission. What the implications are of these findings for clinical practice and/or further research: Though the majority of these flares were not major and did not require hospitalisation, these patients usually have a bad obstetric history. However, with multidisciplinary involvement, SLE activity in our series was not an independent predictor of a poor pregnancy outcome.

BACKGROUND Premature atherosclerosis is observed in systemic lupus erythematosus (SLE). Oxidative modification of LDL is associated with atherosclerotic plaque formation. OBJECTIVES We hypothesized that anti-oxidized LDL (oxLDL) and anti-phospholipid (APL) in SLE sera would segregate with specific antibody subsets, and that anti-oxLDL antibodies will linger in circulation over an extended period. PATIENTS AND METHODS Sixty-seven SLE and control subjects and two SLE subjects with sera collected longitudinally for 13 years were tested for anti-oxLDL and IgG/IgM/IgA APL antibodies. RESULTS Anti-oxLDL ELISA values above 57.48 Activity Units (AcU) (means of normals + 3 standard deviations) and anti-IgG/IgM/IgA APL above 10 phospholipid units (PU) were considered positive. Average anti-oxLDL was 67.7 ± 50.5 AcU in SLE compared to 23.9 ± 11.19 AcU in normals (P = 0.018). Ten out of ten subjects with anti-Ro60/anti-La/anti-Ro52 antibodies had highly significant (P < 0.0001) anti-oxLDL (127.29 ± 45.67 AcU) and IgG APL (18.66 ± 7.4 PU) (P < 0.02). Subjects with anti-RNP were positive for anti-oxLDL (P < 0.002), but subjects with anti-Ro60/anti-Ro52 and subjects negative for extractable nuclear antigen (ENA) antibody were not positive for anti-oxLDL. Anti-oxLDL/anti-IgG APL remained significantly elevated in two patients studied longitudinally. Interestingly, one developed anti-oxLDL/anti-APL antibodies several years before anti-Ro60 development. CONCLUSIONS Presence of antibodies against Ro RNP and La, and RNP is highly associated with developing anti-oxLDL and APL antibodies in SLE. It will be clinically important to see if cardiovascular events occur in these SLE subsets having elevated anti-oxLDL and APL antibodies. Emergence of anti-oxLDL/IgG APL before anti-Ro60 over time in a patient indicates that these antibodies could not be cross-reactive in nature, at least in this particular patient.

Summary. The antiphospholipid-syndrome (APS) is one of the most severe forms of thrombophilia, which may not only lead to recurrent venous but also to arterial thromboembolic events (TE), and to severe pregnancy complications, respectively. APS is defined by clinical symptoms and specific laboratory findings: 1. Lupus anticoagulant (LA), 2. anticardiolipin-antibodies (ACA), and 3. β2-Glycoprotein I-antibodies (β2GPI-Ab). All test results have to be confirmed after at least 12 weeks. The thrombotic risk is highest, if all 3 test groups are positive. It must be pointed out that the presence of UFH, VKA or DOACs may lead to false positive LA-test results; the addition of a specific absorber after blood sampling may provide reliable results in the presence of DOACs. A prospective randomized controlled trial comparing warfarin and rivaroxaban (TRAPS-trial) including only high-risk patients with triple positive APS was terminated early because of an increased rate of TE in patients treated with rivaroxaban [19 %, mostly arterial, compared to 3 % with warfarin (HR 7.4;1.7–32.9)]. Subsequently, a warning letter was issued by the pharmaceutical manufacturers of DOACs, including a warning of DOAC use in APS-patients, particularly in triple-positive high-risk patients. Conclusions: 1. Clinical suspicion of APS requires careful diagnostic testing. Because of inadequate diagnostic workup, many patients may not even have an APS, and these patients could be adequately treated with a DOAC. 2. Patients with single or double positive antiphospholipid antibodies but without positive LA may have a comparably low thrombotic risk and may also be treated with a DOAC in venous TE – sufficient evidence for that conclusion is not yet available but is suggested by the results of meta-analyses. 3. Triple positive patients or those with APS who suffered from arterial thromboembolism have a very high recurrence risk of thrombosis; the TRAPS-Study shows that these patients should be treated with VKA instead of a DOAC.

A 48-year-old woman with severe pain and numbness of her right leg and foot was admitted to our hospital. She had never smoked and had little exposure to passive smoking. Initially, polyarteritis nodosa with anti-phospholipid antibodies was considered. Combination therapy with methylprednisolone pulse therapy, intravenous cyclophosphamide pulse therapy, vasodilators, antiplatelet agents, and anticoagulants was not effective. Vasculopathy was progressive, and she presented with gangrene of the toes. She required amputation of her right leg. The pathological findings of the amputated leg revealed thromboangiitis obliterans (TAO). TAO should be considered even in non-smoking women. Non-response to immunosuppressant and anticoagulant therapies may be a clue to the diagnosis of TAO.

Background Nailfold capillaroscopy (NC) is a simple and non-invasive diagnostic technique, able to investigate microvascular features. In subjects with anti-phospholipid autoantibodies (aPL) many different endothelial abnormalities have been described. Objectives We aimed to investigate the role of NC in aPL positive (aPL+) subjects, highlighting the main microvascular alterations, detected by NC. Methods We enrolled 39 patients with primary anti-phospholipids syndrome (pAPS) (32 females, mean age 43 years, mean disease duration 7 years), 47 patients with secondary anti-phospholipis syndrome (sAPS) due to Systemic Lupus Erythematosus (36 females, mean age 44 years, mean disease duration 15.5 years) and 17 aPL+ subjects without any autoimmune disease, defined as aPL carriers (16 females, mean age 42 years). All subjects underwent clinical and laboratory evaluations as well as NC with both characterization of morfological parameters and attribution of a semiquantitative score. Results The main NC findings were: morphological alterations (tortuous, bushy and/or ramified capillary) in 100% patients with pAPS, in 77% sAPS patients and in 88% aPL carriers; microhaemorragies in 56% pAPS patients, in 49% sAPS patients and 24% aPL carriers; enlarged hairpins in 23%, 41% and 18% subjects with pAPS, sAPS and aPL carriers respectively. In 6.3% sAPS patients, an early scleroderma pattern was detected. A NC semiquantitative score 1 was found in 58.9% pAPS patients, in 57.4% sAPS patients and in 70.5% aPL carriers. Among those cases with abnormal NC findings, we found that a higher NC score (>2) was significantly more frequent in pAPS (21.7%) and sAPS (22.2%) patients respect to aPL carrier cases (8.3%) (p We also found, among the main cardiovascular risk factors, that a higher score (1) was significantly associated with the presence of diabetes mellitus in pAPS patients (p Conclusion Our findings show that some NC aspecific abnormalities are more frequently found in aPL positive subjects, mainly in pAPS and sAPS ones. Altough not specific, such NC features seem to be associated with the presence of vascular risk factors. Thus NC could be regarded as a useful tool in order to evaluate microcirculation in aPL positive cases. References [1] Tavakol MEet al, Biomed Res Int2015; 2015: 974530. [2] Maricq HRet al, Arthritis Rheum1980; 23: 183 – 188. [3] Vaz JLPet al, Rheumatology2004;43:1025–7. [4] Sulli A, J Rheum2000;27:1574–6. [5] Aslanidis S, Clin Exp Rheum2011;29:307–9. Disclosure of Interests massimiliano vasile: None declared, Katia Stefanantoni Consultant for: Only 1 scientific advice for Italfarmaco in 2016, Fulvia Ceccarelli: None declared, Elena Marafioti: None declared, fabrizio conti: None declared, Valeria Riccieri: None declared, Guido Valesini: None declared

BACKGROUND Increasing interest has focused on the development of new assays more specific for APS and application of multiple combinations of anti-phospholipid antibodies (aPLs). This study explored the thrombotic risk of non-criteria aPLs measured by a new line immunoassay (LIA) and the benefit of additional non-criteria aPLs results to the APS diagnosis. METHODS LIA were performed to detect 9 aPLs in 180 patients requested for lupus anticoagulant (LA) measurement. Antibodies against anti-cardiolipin (CL), β2 glycoprotein I (GPI), and β2GPI domain I were measured by ELISA. RESULTS The agreement percentages for IgG/IgM anti-CL and anti-β2GPI between ELISA and LIA (anti-CL 68.2% and 82.6%; anti-β2GPI 71.7% and 93.2%, respectively). Among 9 aPLs measured by LIA, single presence IgG of anti-phosphatidylserine (odds ratio (OR) 16.477) and anti-phosphatidic acid (OR 9.625) predicted higher thrombotic risk than anti-β2GPI (OR 5.538). Other aPLs measured by LIA (anti-prothrombin, anti-annexin V, anti-phosphatidylinositol, phosphatidylethanolamine, and anti-phosphatidylglycerol) did not show any significant thrombotic risk. Addition of the 2 non-criteria aPLs (anti-phosphatidylserine and anti-phosphatidic acid) to the established APS criteria increased the diagnostic specificity and accuracy for thrombosis. The positive rates of anti-β2GPI and anti-phosphatidylserine measured by LIA were quite high in patients with positive anti-β2GPI domain I. CONCLUSIONS The anti-phosphatidylserine and anti-phosphatidic acid among non-criteria aPLs have a high likeli-hood as new markers for thrombotic prediction.

Background:A higher prevalence of ischemic heart disease (IHD) in patients with systemic sclerosis (SSc) was reported. However, contrasting findings were published concerning the role of SSc-related autoantibodies in IHD risk which remains controversial.Objectives:The current study explored the link between SSc and IHD, impact of putative links on SSc mortality and the role of SSc-related and antiphospholipid autoantibodies in disease associated IHD.Methods:A large cohort study utilising the Clalit-Health-Service (CHS) database was conducted on 2,431 SSc patients and 12,710 age- and sex matched controls. The proportion of IHD was compared between patients diagnosed with SSc and age- and gender-matched controls. The role of SSc-linked and antiphospholipid autoantibodies in disease associated IHD was assessed.Results:The rate of IHD was significantly higher in SSc than controls (20.4%vs15.0%, pConclusion:Patients with SSc are at higher risk for developing IHD with an additional risk for the latter in those positive for aCL or anti-beta2GPI. A high degree of suspicion is needed during routine patient follow-up and pre-emptive screening should be considered.Disclosure of Interests:Abdulla Watad: None declared, Dennis McGonagle Grant/research support from: Janssen Research & Development, LLC, Nicola Luigi Bragazzi: None declared, Doron Comanesther: None declared, Arnon Cohen: None declared, Merav Lidar: None declared, Howard Amital: None declared

Background:Anti-phospholipid syndrome (APS) is an important cause for recurrent pregnancy losses (RPL). Conventional APS antibodies (aPLs) like lupus anti-coagulant (LA), anti-cardiolipin(ACL) and anti-beta 2 glycoprotein I (anti-β2 GP I) are not present in significant number of obstetric APS(OAPS) patients, leading to a state described as “ sero-negative” OAPS (SNOAPS). Recent literature shows non-conventional aPLs like Anti phosphatidylserine-prothrombin complex (Anti-PSPT) and Anti-Annexin V (Anti-Ann V) can be positive in up to 50% of SNOAPS patientsObjectives:Testing the performance of conventional and non-conventional aPLs in suspected OAPS patients (obstetric events as defined in the Sydney classification criteria for APS)Methods:We performed a retrospective chart review of 101 patients who underwent combined testing for non-conventional aPLs for suspected OAPS from May 2016 to November 2019 at our department. Patients were categorized into OAPS cases (n=50, median age 31 years) and controls (n=51, median age 30 years) based on their fulfillment of clinical definition of OAPS events defined by Sydney criteria. Conventional aPLs were tested by methods adapted in Sydney criteria and Anti PSPT /Anti Ann V were tested by commercial ELISA. The sample size(n=101) has 95% confidence interval with a margin of error of 10% for the objective of the study.Results:36 cases (72%) were ‘sero-positive’ & 14 cases (28%) were truly ‘sero-negative’ for conventional aPLs. 5 (35.7%) of the SNOAPS patients were positive for Ant-PSPT and/or Anti AnnV antibodies. Performance of the various aPLs in suspected OAPS is displayed in Table 1 & Figure 1.Table 1showing the performance of the various conventional and non-conventional APLs in suspected obstetric APS casesAntibodySensitivitySpecificityLikelihood Ratio(+)Likelihood Ratio (-)Positive Predictive ValueNegative Predictive ValueAccuracyYouden’s IndexLA50%94.1 %8.50.589.3%65.7%72.3%44.1%ACL32%98%16.30.794.1%59.5 %65.3%30 %anti β2 GP I IgM38.4%91.4 %4.50.783.3%57.1 %63.5%29.8%anti β2 GP I IgG24%96.1 %6.10.885.7%56.3%60.4%20.1%Anti PSPT28%96.1 %7.10.787.5%57.6 %62.4%24.1%Anti AnnV28%98 %14.30.793.3%58.1%63.4%26%Conventional APLs72%88.2%6.10.385.7%76.3 %79.8%60.2%Non-conventional APLS38%94.1%6.40.786.4%60.7 %66.3%32.1%All APLs82%86.3%6.000.2085.4%83 %84.2%68.3%Figure 1showing the comparative diagnostic performance of Conventional aPL testing vs Combined testing along with non-conventional aPLs in suspected obstetric APS scenarioConclusion:In a delicate situation like RPL, performance of non-conventional aPLs on their own, though not as sensitive as conventional aPLs, still demonstrate better specificity. Non-conventional APLs can newly identify 1/3rd of SNOAPS as APS. The real value of testing Anti PSPT & Anti Ann V in RPL, is combined testing with conventional aPLs wherein they improve the sensitivity and accuracy of diagnosis of OAPS by 10% & 4.4 % respectively, with only 1.9% drop in specificity. Non-conventional aPLs should be tested in SNOAPS.Disclosure of Interests:None declared

Right atrial (RA) thrombi are uncommon and usually present as a complication of central venous catheter placement. RA thrombus secondary to oral contraceptives (OCP) or anti-phospholipid antibody syndrome (APS) has never been reported. A 24 year old female on OCP and history of mitral valve

There is little information about pregnancy outcomes in patients with active membranous nephropathy (MN), especially those with circulating autoantibodies to M-type phospholipase A2 receptor (PLA2R), the major autoantigen in primary MN. Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space, frequently associated with circulating M-type phospholipase A2 receptor. Nephrotic syndrome (massive proteinuria and hypoalbuminemia) at diagnosis predicts poor prognosis. Pregnancy with active MGN is high risk for foetal loss, intrauterine growth restriction, and pre-eclampsia, and may worsen maternal renal function, especially with the presence of antiphospholipid antibody syndrome (APLA). We report a 23-year-old gravida in her first pregnancy, suffering from MGN and severe nephrotic syndrome, complicated by APLA syndrome. The patient was treated with enoxaparin, aspirin azathioprine, and Prednisone for a short time, in addition to furosemide and albumin intravenously. She was delivered at 30 weeks due to deteriorating maternal and foetal conditions. A successful neonatal and maternal outcome was achieved in this case. The patient's history revealed thrombocytopenia and APLA syndrome and continues to be treated chronically with enoxaparin. Kidney biopsy performed after delivery showed membranous MGN stage II-III. Herein, we present a case of successful pregnancy and foetal outcome in a young woman with APLA syndrome and MN. Keywords: Membranous GN, Nephrotic Syndrome, Anti-Phospholipid Antibodies.

Immunoglobulin (Ig) G- and IgM-class anti-cardiolipin antibodies (aCL) and lupus anti-coagulant (LA) are included in the 1997 update of the American College of Rheumatology (ACR-97) systemic lupus erythematosus (SLE) criteria. Despite limited evidence, IgA-aCL and IgA anti-(2)-glycoprotein-I (anti-(2)GPI) were included in the 2012 Systemic Lupus International Collaborating Clinics criteria. The present study aimed to evaluate IgG-/IgA-/IgM-aCL and anti-(2)GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy, anti-phospholipid syndrome (APS) and organ damage among 526 Swedish SLE patients meeting ACR-97. Patients with rheumatoid arthritis (n=100), primary Sjogrens syndrome (n=50) and blood donors (n=507) served as controls. Anti-phospholipid antibodies (aPL) were analysed by fluoroenzyme-immunoassays detecting aCL/anti-(2)GPI. Seventy-six (14%) SLE cases fulfilled the Sydney APS-criteria, and 1 aCL/anti-(2)GPI isotype (IgG/IgA/IgM) occurred in 138 SLE patients (26%). Forty-five (9%) of the SLE cases had IgA-aCL, 20 of whom (4%) lacked IgG-/IgM-aCL. Seventy-four (14%) tested positive for IgA anti-(2)GPI, 34 (6%) being seronegative regarding IgG/IgM anti-(2)GPI. Six (1%) had APS manifestations but were seropositive regarding IgA-aCL and/or IgA anti-(2)GPI in the absence of IgG/IgM-aPL and LA. Positive LA and IgG-aPL tests were associated with most APS-related events and organ damage. Exclusive IgA anti-(2)GPI occurrence associated inversely with Caucasian ethnicity [odds ratio (OR)=021, 95% confidence interval (CI)=006-072) and photosensitivity (OR=019, 95% CI=005-072). Nephritis, smoking, LA-positivity and statin/corticosteroid-medication associated strongly with organ damage, whereas hydroxychloroquine-medication was protective. In conclusion, IgA-aPL is not rare in SLE (16%) and IgA-aPL analysis may have additional value among SLE cases with suspected APS testing negative for other isotypes of aPL and LA. Funding Agencies|Swedish Society for Medical Research; Swedish Rheumatism Association; Swedish Society of Medicine; King Gustaf Vs 80-year foundation; King Gustaf V and Queen Victorias Freemasons foundation; Swedish Heart-Lung Foundation; Swedish Research Council; County Council of Stockholm; County Council of Uppsala; County Council of Ostergotland

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

Background In case of anti-phospholipid syndrome, anticoagulants are recommended. However, there were no data about recurrence rate for thrombosis in patients with anti-phospholipid antibodies (APS) initially which disappeared later. Objectives We compared recurrence rate of thrombosis between negative conversion group and control group. Methods We reviewed the medical records of patients diagnosed with thrombosis such as cerebral infarct, myocardial infarct, deep vein thrombosis, or thrombosis of other vessels at a tertiary medical center from 2000 to October 2016. Of these, 14 patients whose APA status was converted from positive to negative after more than 12 weeks were enrolled as negative conversion group. Forty-six patients without APA were matched with the ratio of 1:3∼1:4 according to age, sex, thrombosis type (arterial or venous) and therapeutic agents as control group. Results There was no difference between negative conversion group and control group in smoking status, presence of diabetes or hypertension, duration from the thrombosis to last visits or to recurrence, the proportion of patients taking glucocorticoids. There was no difference in the overall recurrence of thrombosis between two groups [negative conversion group, 3/14 (21%) vs. control group, 6/46 (13%), p=0.423]. In the negative conversion group, the number of patients diagnosed with SLE was significantly higher than the control group [SLE, 3/14 (21%) vs. 1/46 (2%), p=0.036]. However, thrombosis had recurred in one out of three patients with SLE. Conclusions The cumulative incidence of thrombotic events was not significantly different between negative conversion group and control group. Disclosure of Interest None declared

Purpose To explore the role of plasmatic platelet-activating factor acetylhydrolase (PAF-AH), a marker of cardiovascular risk, in patients with anti-phospholipid antibodies (aPL). Methods PAF-AH activity was assessed in a series of 167 unselected patients screened for aPL in a context of thrombotic events, risk of thrombosis or obstetric complications and in 77 blood donors. Results 116/167 patients showed positive results for at least one aPL among IgG/IgM anti-prothrombin/phosphatidylserine (aPS/PT), anti-cardiolipin (aCL), anti-beta2-glycoprotein I (aβ2GPI) or lupus anticoagulant (LAC), while 51/167 patients resulted aPL-negative. LAC+ patients disclosed higher PAF-AH than LAC-negative (22.1 ± 6.4 nmol/min/ml vs. 19.5 ± 4.1 nmol/min/ml; p = 0.0032), and aPL-negative patients (p = 0.03). Patients presenting positive IgG aβ2GPI disclosed higher PAF-AH than patients with only IgM aβ2GPI-positive antibodies (23.1 ± 7.2 nmol/min/ml vs. 20.1 ± 5.3 nmol/min/ml; p = 0.035), as well as than patients showing only isolated LAC, aCL or aPS/PT (16.9 ± 3.8 nmol/min/ml; p = 0.003). Conclusions PAF-AH plasmatic activity is particularly up-regulated in LAC+ and in aβ2GPI IgG+ patients, possibly representing an alternative prognostic biomarker for the therapeutic management of APS patients.

Thrombosis associated with acute cytomegalovirus infection has been reported many times in the literature since the mid 1980s – mainly in case reports and in small case series, but also in four controlled studies. Still, many physicians are unaware of this association although acute cytomegalovirus infection diagnosis in a thrombosis patient may warrant antiviral therapy and may affect anticoagulation therapy duration. Accordingly, the clinical characteristics of patients with thrombosis and acute cytomegalovirus infection are reviewed, and the current knowledge concerning this unique association is presented herein. We believe it is time to add acute cytomegalovirus infection to the list of thrombosis triggers.

Even though the association of anti-phospholipid antibodies (aPL) with infertility is debated, infertile women are commonly screened for aPL. To review evidence, a systematic PubMed search was conducted to retrieve papers addressing (i) the association between aPL and infertility, (ii) the positivity rate of criteria and non-criteria aPL in women with infertility, (iii) the association between aPL and assisted reproduction technologies (ART) outcome, (iv) the efficacy of medical treatments on ART outcome, and (v) the effects of ART on thrombotic risk. A total of 46 papers were considered; several limitations emerged: (i) wide heterogeneity in study populations, (ii) non-prospective design in 90% of studies, and (iii) aPL cutoffs not conforming to international guidelines in more than 75% of studies; aPL positivity not confirmed in 89% of studies. Most studies evinced an association between infertility and anti-β2GPI antibodies and almost all non-criteria aPL. The association rate with infertility was below 50% for lupus anti-coagulant, anti-cardiolipin antibodies (aCL), and anti-phosphatidic acid antibodies. According to our estimates, overall positivity rates of criteria and non-criteria aPL tests are 6% and 3% among infertile women, 1% and 2% among controls, respectively. A significant difference in the positivity rate of patients versus controls emerged for aCL only. Five of 18 studies reported a detrimental effect of aPL on ART outcome. Only one of the six studies assessing the effects of treatment on ART outcome among aPL-positive infertile women reported a benefit. All relevant studies reported no increase in the rate of thrombosis among aPL-positive women undergoing ART.