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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.

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.

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.

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 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: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

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.

Resume Le syndrome des anticorps anti-phospholipides (SAPL) associe des manifestations cliniques telles que les thromboses et/ou pertes fœtales a la presence durable d’anticorps anti-phospholipides (aPL). Les aPLs constituent un groupe heterogene d’anticorps detectes par deux methodes: tests de coagulation mettant en evidence un inhibiteur dependant des phospholipides ou lupus anticoagulant et tests immunologiques de type ELISA de dosage des anticorps anti-cardiolipine et anti-β2 glycoproteine 1. Ces dernieres annees la strategie du diagnostic des aPL a fait l’objet d’un effort de standardisation et de simplification mais des avancees sont encore necessaires, notamment le developpement d’etalons mono et/ou polyclonaux. Certaines questions demeurent en suspens, en particulier l’interet des anticorps anti-phosphatidylethanolamine et anti-prothrombine.

SUMMARY Acute myocardial infarction is relatively uncommon in patients under the age of 40 years. Unlike the older patients where rupture of coronary artery atherosclerotic plaque is the main underlying pathology, the pathogenesis in younger patients can be varied and may require different diagnostic and therapeutic approaches. Hypercoagulable state associated with nephrotic syndrome and antiphospholipid syndrome can lead to the development of occlusive coronary artery thrombus in absence of atherosclerotic coronary artery disease. Acute myocardial infarction in such a setting can sometimes be the first manifestation of an underlying disease. We describe a case of myocardial infarction in a young man with both nephrotic and antiphospho-lipid syndromes and present a brief literature review.

Thrombophilia is an inherited or acquired predisposition detected by a set of laboratory tests, which increases the risk for venous thromboembolism or pregnancy complications, as will be discussed. Thrombophilia, as with all other risk factors, should be looked for and modulated according to clinical presentation and risk stratification. Many articles have been written on thrombophilia and pregnancy, but this comprehensive article will focus on the issue from a unique perspective of each thrombophilia separately. This article will elaborate on the main types of thrombophilia and will suggest tools to the treating physician for dealing with thrombophilia during pregnancy. This article is the result of a search of the English literature on PubMed using thrombophilia, pregnancy, complications and thrombosis as keywords.

The antiphospholipid syndrome (APS) is an autoimmune disorder presenting with tissue injury in various organs related to large- or small-vessel thrombosis associated with antiphospholipid and antiprotein/phospholipid complex antibodies. Although the pathophysiology, diagnosis, and clinical scenario may seem clear and straightforward, a more detailed examination reveals a more complex and uncertain picture related to the management of APS. This article reviews the current situation relating to APS therapy by evaluating the different clinical features of the syndrome ranging from thrombosis to pregnancy complications together with new strategies and pharmacological approaches.

The catastrophic anti-phospholipid syndrome (CAPS) differs from the anti-phospholipid syndrome in its accelerated systemic involvement leading to multi-organic failure. In this study, the occurrence of malignancies in patients with CAPS was evaluated and the clinical findings of CAPS patients with and without malignancies were compared. We investigated the web site-based international registry of patients with CAPS for all cases in which both CAPS and underlying malignancies were present. The clinical characteristics of these cases were subsequently evaluated to establish common characteristics. The CAPS registry included information on a total of 262 cases. Twenty-three (9%) patients suffered from malignancies. In 78% of these patients, the malignancy itself or the treatment modalities instituted for the carcinoma was the precipitating factor of CAPS. Only 39% of CAPS patients with malignancies recovered in comparison to 58% of patients without malignancies (p = 0.07). Treatment modalities, however, did not differ significantly between these patients. Infections were not evident as precipitating factors for any of the malignancy patients. The mean age of patients with malignancies was 9 years older than the average age of other patients with CAPS and the prevalence of SLE was significantly less common than in patients without malignancy. Malignancy may play a pathogenic role in patients with CAPS, whereas infections are more important as triggering factors in patients without malignancies. CAPS patients with malignancies are generally older than CAPS patients without malignancies; they generally have the worst prognosis of the entire CAPS cohort.

To determine the prevalence and clinical correlates of anti-phospholipid antibodies (aPL), including anti-cardiolipin antibodies (aCL), lupus anti-coagulant (LA), anti-beta2-glycoprotein 1 (abeta2GP1), and anti-prothrombin (aPT) antibodies, in Black South African patients with systemic lupus erythematosus (SLE).A cross-sectional study of 100 SLE patients in whom clinical characteristics, including features of the anti-phospholipid syndrome (APS), disease activity, and damage were documented, and sera tested for aCL, abeta2GP, and aPT of all isotypes, and LA.Positive aCL, abeta2GPI, aPT, and LA were found in 53, 84, 20, and 2 patients, respectively. Immunoglobulin (Ig)A aCL and IgG abeta2GPI were the commonest aCL (49.1%) and abeta2GPI (47%) isotypes, respectively. IgA abeta2GPI were associated with both a history of thrombosis alone (p0.05) and a history of any clinical feature, thrombosis, and/or spontaneous abortion of the APS (p0.05); IgA aCL were associated with a history of any clinical APS event (p0.05); and abeta2GPI of any isotype were associated with a history of arthritis (p0.001).Our findings provide further evidence that screening for abeta2GPI and IgA aCL isotypes may improve the risk assessment for APS in SLE patients of African extraction. Further prospective studies are warranted to determine the clinical utility of these tests and to elucidate the genetic basis for the increased IgA aPL response in SLE patients of African extraction.

Rheumatologists are increasingly involved in the care of young women who, in the age of biologic therapy, are now gaining control of their rheumatic diseases and attempting pregnancy. With careful planning, most women with rheumatic diseases have successful pregnancies. This article focuses specifically on the highest-risk pregnancies and controversial areas. We discuss the women at risk of complications, the types of maternal and fetal complications, the treatments that can be used in pregnancy (and breastfeeding) and longer-term outcomes that could affect the mother. SLE, RA, ANCA-associated vasculitides, large vessel vasculitis (e.g. Takayasu's) and other CTDs (e.g. scleroderma) are among the conditions covered. The evidence and controversies regarding the recommendations for the use of biologics in pregnancy are discussed. The role of the rheumatologist in pregnancy planning and caring for the pregnant and post-partum woman as part of the multidisciplinary team is discussed.

Resume Le syndrome des antiphospholipides constitue une entite clinicobiologique associant des manifestations cliniques principalement a type de thromboses veineuses et arterielles et de fausses couches repetees a des manifestations biologiques liees a la presence d’anticorps antiphospholipides. Les anticorps antiphospholipides representent une famille tres heterogene d'anticorps. En effet, de nombreux travaux ont montre que ces anticorps n'etaient pas seulement diriges contre les phospholipides anioniques seuls, mais pouvaient aussi reconnaitre des phospholipides fixes a des cofacteurs proteiques plasmatiques ou aux cofacteurs eux-meme. L'heterogeneite des anticorps antiphospholipides et le manque de standardisation des techniques rendent delicate l’interpretation biologique et clinique des resultats. Le but de cet article est de faire le point sur les nouvelles donnees cliniques de ce syndrome et sur les tests biologiques disponibles dans le domaine de la coagulation et des tests immunologiques. L’interet clinique des tests biologiques est egalement discute.

Resume De nombreuses affections auto-immunes peuvent se manifester par des complications justifiant une prise en charge en reanimation. Cette prise en charge urgente necessite que lˈon ait la capacite dˈetablir rapidement un diagnostic etiologique, en particulier grâce a lˈutilisation dˈauto-anticorps qui peuvent etre de pertinents marqueurs diagnostiques et parfois pronostiques. Ces auto-anticorps peuvent etre utiles pour lˈexploration dˈun syndrome thrombotique ou de complications viscerales, surtout pulmonaires et renales, evoquant un syndrome des anti-phospholipides, un lupus, une vascularite, un syndrome de Goodpasture ou plus rarement une autre affection auto-immune. Dans ces differentes situations urgentes, les auto-anticorps susceptibles dˈetre recherches sont les antiphospholipides, les anticytoplasmes des polynucleaires (ANCA), les anticorps antinucleaires et anti-ADN natifs, les antimembranes basales glomerulaires et alveolaires ou plus rarement dˈautres specificites. En routine, ces auto-anticorps sont des outils diagnostiques et parfois pronostiques a condition dˈeviter un certain nombre de pieges lies a lˈexistence dˈauto-anticorps non specifiques. Ces pieges peuvent etre evites par une bonne connaissance de la valeur de ces marqueurs et par une collaboration avec un laboratoire de reference.

This editorial refers to Low-dose aspirin versus low-dose aspirin plus low-intensity warfarin in thromboprophylaxis: a prospective, multicentre, randomized, open, controlled trial, in patients positive for antiphospholipid antibodies (ALIWAPAS), by Maria J. Cuadrado et al., doi:10.1093/rheumatology/ket313, on pages 275-84.

To evaluate the agreement and performance of two tests for aPLs with regard to association with manifestations of the APS in patients with SLE.We investigated 712 SLE patients and 280 population controls. Cardiolipin and β(2) glycoprotein-I antibodies were measured with routine ELISA and a new automated method. Three positivity cut-offs (99%, 90% of controls and recommended cut-off by manufacturers) were used. Associations with previous thrombotic events, thrombocytopenia and, in a subgroup of patients, obstetric morbidity (n = 296) were evaluated. Results were compared with the LA test, performed in 380 patients.Inter-test agreement was moderate (demonstrated by κ-values 0.16-0.71). Performance of the two tests was similar: at the 99th percentile cut-off, sensitivity for any thrombotic event ranged from 3.7% to 24.8%, while specificity was 84.7-97.7%. Regardless of assay, IgG isotypes were associated with venous thrombosis and ischaemic cerebrovascular disease, whereas aPLs of IgM isotype were weakly associated with ischaemic heart disease. Associations were greatly affected by aPL level. LA performed better than the specific aPL tests. LA was associated with any thrombotic event, odds ratio 5.4 (95% CI 3.1, 9.4), while the specific aPL tests ranged from non-significant to an odds ratio of 1.9 (95% CI 1.03, 3.4) using criteria cut-off. LA was also convincingly associated with other APS manifestations.In relation to thrombotic manifestations, there was moderate agreement but no clear advantages when comparing a routine aPL ELISA with an automated method. APL isotype and titre as well as LA positivity are important for risk assessment in SLE patients.

Rhupus syndrome is a rare syndrome characterized by overlap of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Our patient was a diagnosed case of RA and developed SLE 2 years after. She was a middle-aged woman, presented with bilateral pleural effusion with exacerbation of skin and joint symptoms of SLE. We diagnosed the case as tubercular pleural effusion by positive Mycobacterium tuberculosis in bactec 460 culture. She had also anti-phospholipid antibody positivity without any symptoms and signs of thrombosis.

A young woman aged 23 experienced binocular partial amaurosis fugax attacks for at least one year with crescendo frequency. Clinical and laboratory evaluations were normal except for the demonstrat...

A 12-year-old African American boy with mental retardation and Asperger's disorder presented with acute psychosis. Antiphospholipid antibody testing with enzyme-linked immunosorbent assay showed increased levels of immunoglobulin G anticardiolipin antibodies in the cerebrospinal fluid, but not in the serum. Although antiphospholipid antibodies have been reported in the serum of patients with thrombotic and neurologic disorders, there are only a few reports of these antibodies in cerebrospinal fluid. This finding is consistent with a recent report of antiphospholipid antibodies found in the cerebrospinal fluid of adults with acute psychosis.

Anti-phospholipid syndrome includes a variety of clinical manifestations, among which is recurrent pregnancy loss. Recently, it was suggested that anti-phospholipid antibodies might also have a role in infertility, mainly in unexplained infertility. Most of the studies report about an increased prevalence of these antibodies in infertile women; however, data regarding the implication of these antibodies on treatment outcome (mainly in in-vitro fertilization) and if there is a beneficial effect of treating these patients with aspirin, heparin and prednisone--remains still controversial. In this communication we review the literature reports of association of anti-phospholipid antibodies and infertility, and deal with the question whether they have a pathogenic role in these cases.

Patients with antiphospholipid antibodies may suffer from thrombotic events and recurrent spontaneous abortions. A defective fibrinolytic potential has been described in women with recurrent fetal losses. We investigated the prevalence of anticardiolipin antibodies and of various fibrinolytic abnormalities in 64 females with a history of at least two abortions of unknown origin. Anticardiolipin antibodies were present in the serum of 31 patients (48.4%). The overall prevalence of fibrinolytic disorders was 67.2% (43 cases) and resulted significantly higher than that of aCL positivity (P = 0.03). In most of cases the impaired fibrinolytic potential after venous occlusion test was due to increased PAI-1 levels; only in a few instances a defective fibrinolytic response was due to reduced t-PA release, a combined defect or an intrinsic fibrinolytic deficiency. After division of patients in two groups on the basis of the aCL presence, the distribution of different fibrinolytic defects was similar in aCL positive and negative women, suggesting the lack of correlation between hypofibrinolysis and aCL antibodies. Plasminogen abnormalities resulted compatible with congenital hypoplasminogenemia in two aCL negative women, whereas in four aCL positive patients they were suggestive for acquired dysplasminogenemia. Our results indicate that patents with recurrent spontaneous abortions may present fibrinolytic disorders, which occur independently and more often than aCL positivity. An accurate investigation of the fibrinolytic potential, and, namely, of PAI-1 levels, should be included in the study of females suffering from repeated fetal losses. © 1994 Wiley-Liss, Inc.