Presence Of Lupus Anticoagulant Research Articles

Clot-Based Assay for Factor XI (FXI) Activity Is Highly Sensitive to Lupus Anticoagulant (LA) and Heparin with Potential Misdiagnosis of FXI Deficiency: The Importance of Recognizing Non-Parallelism

Introduction: Clot-based assays are employed to estimate coagulation factor activity in clinical pathology laboratories. These assays are PT- or aPTT-based and utilize dilutions of the patient's plasma in factor-deficient plasma. The curves of activity for each dilution follow a parallelism or non-parallelism pattern and the latter is typically seen in the presence of Lupus Anticoagulant (LA). Identification of this pattern is critical to avoid misdiagnosis of factor deficiency in patients who actually have an inhibitor. Materials and Methods: We observed low Factor XI (FXI) levels in patients with LA, while other factors were not affected. In order to determine the reason(s) why FXI levels are sensitive to LA, we collected 34 plasma samples from patients with dRVVT confirm ratio > 1.2, and estimated FVIII and FXI levels. FXI activity was also estimated with Dade ® Actin ® FS, a reagent that is not sensitive to the LA. The coefficient of variance (CV) for both FXI and FVIII levels were compared. To estimate the effects of heparin, plasma was spiked (0.1-1.0 IU/ML) and tested in the PTT, FXI, and FVIII assays. We tested with Dade ® Actin ® FS 4 known normal patients, 3 known FXI deficient patients, 20 known plasma positive for LA, and 10 with heparin. All assays were performed on a Siemens CS-5100 analyzer. Results: The results show that FXI is highly sensitive to LA, with non-parallelism and high CV, not observed with FVIII activity. As expected, FXI levels were not affected when LA-insensitive Dade ® Actin ® FS was used. Heparin (0.3-0.7 IU/ML) also showed non-parallelism in FXI activity, but not for FVIII. Only the highest dose of heparin (1.0 IU/ML) affected FVIII levels. Notably, the sensitivity of FXI activity to LA and heparin was explained by a few dilutions of the patient's plasma (5X) in the FXI assay, compared to other coagulation factors (20X). Of note, less diluted plasma is required for FXI activity because relatively higher levels of FXI is required to sustain and produce clot in the FXI-deficient plasma. Conclusion: This simple, yet not recognized explanation based on a literature search, is helpful to increase awareness of this analytical variable. It is also important to avoid misdiagnosis of FXI deficiency in patients with LA.

Myocardial fibrosis associates with lupus anticoagulant in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that carries increased risk of cardiovascular disease; however, the underlying pathophysiological mechanisms remain poorly understood. We aimed to investigate the prevalence and degree of myocardial fibrosis in SLE patients and associated disease characteristics. Forty-nine SLE patients (89% female, mean age 52 ± 13 years, median disease duration 19 (11–25) years) and 79 sex-and age-matched healthy controls were included. CMR with T1 mapping was performed on SLE patients and healthy controls. Fifty-one SLE patients received gadolinium contrast for the evaluation of late gadolinium enhancement (LGE) and extra cellular volume (ECV). Multiple linear regression analyses were performed to investigate the association between markers of myocardial fibrosis on CMR (LGE, T1, ECV) and SLE-related variables [clinical disease activity, lupus nephritis, chronic kidney disease, anti-cardiolipin and/or anti-beta-2 glycoprotein I antibodies, and lupus anticoagulant (LAC)] with adjustment for traditional risk factors. T1 values were elevated in SLE patients compared to healthy controls (1031 ± 36 ms vs. 1019 ± 25 ms, p = 0.01). LGE was present in 20% of SLE patients who received gadolinium contrast. On multivariable analysis, LAC was associated with LGE in SLE patients (β = 3.87, p = 0.02). Neither T1 nor ECV associated with SLE disease characteristics; however, there was a trend towards an association between LAC and T1 (β = 16.9, p = 0.08). SLE patients displayed signs of myocardial fibrosis on CMR that were associated with the presence of LAC. These findings support the pathophysiological understanding of LAC as a mediator of microvascular and subsequent myocardial dysfunction.Graphical abstract

B-093 Evaluation of the Association of Non-criteria Antiphospholipid Antibodies with the Presence of Lupus Anticoagulant

Abstract Backrground Laboratory diagnosis of the antiphospholipid antibody syndrome (APS) requires evidence ofpersistently positive lupus anticoagulant (LAC), detected using clot-based assays and/or thepresence of high-titer serum anti-cardiolipin (aCL) and/or anti-beta-2 glycoprotein-1 (aB2GPI)antibodies, measured by semi-quantitative solid-phase immunoassays. Several non-criteria anti-phospholipid antibodies (NC-APLA) have been proposed as candidates for APS diagnosis:phosphatidyl-serine/ prothrombin (aPS/PT; IgM and IgG isotypes), anti-phosphatidyl serine (aPS;IgM and IgG), anti-prothrombin (aPT-IgG). However, their diagnostic relevance in routine APSevaluation is still unclear. The objectives of this study were 1) to determine the prevalence andassociation of NC-APLA in relation to LAC, aCL and aB2GPI antibodies’ positivity,independently and in combination and, 2) to assess the ability of NC-APLA to predict LACactivity, as an indirect measure of their function. Methods Results from 492 patients submitted for antiphospholipid antibody (APLA) panel or standaloneserology testing between January 2016 to January 2023 were retrieved in accordance withinstitutional guidelines. Patients were grouped according to LAC status and serology positivity(using manufacturer-suggested cutoff) into three groups: Single-positives (SP) for LAC, aCL oraB2GPI; Double-positives (DP) for aCL and aB2GPI; Triple-positives (TP) for LAC, aCL andaB2GPI. NC-ALPA titers were compared between LAC-positive and negative patients. Statisticalsignificance was established using unpaired Student’s t-test. Receiver operating curve (ROC)analysis was employed to assess the ability of NC-APLA to predict LAC status. Results Out of the total 492 patients, 1.8% (9/492) were TP, 2.4% (12/492) were DP and 24.7% (122/492)were SP. All NC-APLA titers were significantly higher in TP than in SP patients (P < 0.001).aPS/PT IgG (Mean: 76.3 vs 12.8 Units) and aPS IgG (Mean: 64.8 vs 5.5 GPS) antibodies weresignificantly higher in TP than DP patients (P = 0.008 and <0.0001, respectively). aPS/PT IgM(Mean: 62.5 vs 19.4 Units) and aPS IgM titers (Mean 31.9 vs 7.7 MPS) were significantly higherin DP compared to SP patients (P < 0.0001). When classified by LAC status, 40 patients werepositive and 452 were negative. Levels of all NC-APLA antibody titers (P < 0.0001) followed byaCL (Mean IgG 21.9 vs 7.8 GPL; IgM 20 vs 12.6 MPL; P < 0.01) and aB2GPI (Mean IgG 20.1 vs 4.9 SGU; IgM 13.8 vs 7.6 SMU, P < 0.001) antibodies were significantly higher in LAC-positivepatients compared to the LAC-negative individuals. ROC analyses based on the LAC statusresulted in the highest area under the curve (AUC, 95% CI) for aPS/PT IgM (0.72, 0.62 to 0.81)Private Information and aPS/PT IgG (0.74, 0.65 to 0.83) antibodies relative to aCL (IgM:0.53, 0.43 to 0.64; IgG:0.66, 0.56 to 0.77) or aB2GPI (IgM:0.5, 0.51 to 0.72 and IgG:0.6, 0.51 to 0.72) antibodies; aPS IgMand aPT IgG displayed similar performances (0.65, 0.54 to 0.75 and 0.66, 0.57 to 0.74,respectively). Whereas aPS IgG was of lower AUC (0.58, 0.48 to 0.68). Conclusion Our data demonstrated that at high titers, NC-APLA, display increased association with LACpositivity in comparison to aCL or aB2GPI antibody levels. Particularly, aPS/PT antibodiesdisplayed the superior ability to determine the LAC presence.Private Information

A Teenage Boy with Systemic Lupus Erythematosus Complicated with Acquired von Willebrand Syndrome: A Rare Case and Challenging in Making Diagnosis

In systemic lupus erythematosus (SLE), haematological abnormalities are frequent, although they are an uncommon cause of acquired von Willebrand syndrome (AVWS). AVWS is a rare condition that can cause a bleeding disorder. We presented a case of AVWS in the early diagnosis of SLE. One month before admission, the patient had a history of recurrent epistaxis. He presented to the hospital with symptomatic anaemia and was noted to have severe anaemia with iron deficiency. During hospitalisation, recurrent epistaxis recurred and was found to have prolonged activated partial thromboplastin time (aPTT), presence of lupus anticoagulant (LA), and lower von Willebrand factor (VWF), and factor 8 (VIII) levels. Simultaneously, he was diagnosed with SLE based on Systemic Lupus International Collaborating Clinics (SLICC) criteria. He underwent blood transfusions and was treated with immunosuppressive drugs such as steroids, mycophenolate mofetil, and an anti-fibrinolytic agent; he subsequently stopped bleeding and showed clinical improvement.

Evaluating the Relationship Between Antiphospholipid Antibodies and COVID-19 Severity.

Coronavirus 2 (COVID-19) has emerged as a new global pandemic, causing severe acute respiratory syndrome. Furthermore, the existence of antiphospholipid (APL) antibodies (Abs) and ultimately patient death may be linked to the occurrence of thrombotic events in patients with COVID-19. We aimed to investigate if there was a link between the presence of APL Abs and the severity of COVID-19 disease in patients at the Vali-Asr Hospital in Zanjan from June to July 2021. Real-time PCR was used to diagnose COVID-19 in 76 hospitalized patients. A total of 38 patients were hospitalized in the internal medicine ward and another 38 people were admitted to the intensive care unit of the Vali-Asr Educational Hospital in Iran's Zanjan region. Lupus anticoagulant (LAC) detection was done using the dilute Russell viper venom time method, and tests for anticardiolipin (ACL) Abs, IgG and IgM, and anti-beta2 glycoprotein 1 Abs, IgG and IgM, were done on blood and plasma samples of linked patients using the enzyme-linked immunosorbent assay technique. SPSS 24 was used to analyze data. Our findings showed that the presence of LAC was associated with disease severity in COVID-19 patients (p = 0.001). However, there was no significant relationship between APL Abs and mortality in patients affected with COVID-19. The evaluation of APL Abs, particularly LAC, in COVID-19 patients appears to be helpful in predicting the severity of the disease.

Extracellular vesicles released upon stimulation with antiphospholipid antibodies: An actual direct procoagulant mechanism or a new factor in the lupus anticoagulant paradox?

Antiphospholipid antibodies (aPL) lead to a hypercoagulable state in vivo. Paradoxically, some of these autoantibodies perform as inhibitors of the coagulation cascade in vitro (a phenomenon referred to as “lupus anticoagulant”). The presence of lupus anticoagulant has been related to an increased quantity of plasma extracellular vesicles, which may constitute a direct procoagulant mechanism in antiphospholipid syndrome. This study investigates whether or not endothelial cell-derived extracellular vesicles released upon stimulation with aPL (aPL-EDEVs) are related to a higher direct coagulation activity. Using an in vitro model of endothelium, flow cytometry and a recalcified plasma-based assay, we found that the coagulation activity of aPL-EDEVs is mainly conditioned by the lupus anticoagulant-like activity of autoantibodies. Nevertheless, in the presence of β2 glycoprotein I, a cofactor of aPL during the stimulation of endothelial cells, the coagulation activity of EDEVs is restored in a mitogen-activated protein kinase kinases 1 and 2 (MEK1/2)-dependent manner. This phenomenon was especially evident when using immunoglobulins G from patients with vascular and obstetric primary antiphospholipid syndrome who manifest refractoriness to treatment. Our findings suggest that the role of aPL-EDEVs in the antiphospholipid syndrome-related hypercoagulable state may not rely on their capacity to enhance clotting directly. While β2 glycoprotein I performs as a procoagulant cofactor and restores the coagulation activity of extracellular vesicles via MEK1/2 pathway, proportionally, autoantibodies interact with aPL-EDEVs and exhaust their coagulation properties. Further analysis is required to establish whether lupus anticoagulant-like autoantibodies opsonise extracellular vesicles and whether opsonised vesicles may lead to thrombosis by indirect means.

P1622: ANTIPHOSPHOLIPID ANTIBODIES IN CONVALESCENT PLASMA OF DONORS RECOVERED FROM MILD COVID-19

Background: High prevalence of antiphospholipid antibodies (APLA) in patients with COVID-19 has been reported. A meta-analysis concluded that APLA were detected in nearly half of hospitalized patients with COVID-19, and even higher prevalence was found in patients with severe disease.These reports raised questions about the true prevalence and clinical impact of APLA on disease course, long term complications and the prothrombotic influence of COVID-19 convalescent plasma (CCP) transfused to COVID-19 patients. Aims: To evaluate the prevalence of APLA in CCP samples collected from otherwise healthy donors who recovered from mild COVID-19. Methods: CCP was collected from volunteer donors in two time periods (September 2020-January 2021 [early period] and April- May 2021 [late period]). The study was approved by the local ethics committee and all donors and controls signed informed consent. The study was supported by a grant from the Laboratory Research Fund, Shamir Medical Center. Convalescence was supported by studying serum anti COVID-19 antibodies (Ab): Anti- N (nucleocapsid protein) Ab during the early period, and anti- S (Spike1 protein) Ab during the late period.Anti- N Ab were tested by a chemiluminescent immunoassay. Positive results were defined as sample/cutoff (S/CO) ≥1.4. Anti-S1 Ab were tested using ELISA. Results ≥ 50 arbitrary units per milliliter (AU/ml) were considered positive. Plasma samples were tested for APLA: Lupus anticoagulant (LAC)testing was performed using dilute Russell Viper Venom Time (dRVVT) and Silica Clotting Time (SCT). Results were reported as normalized ratios. APLA IgG, IgM and anti-β2-glycoprotein IgG, IgM antibodies were detected using an ELISA method and reported as SGU u/ml or SMU u/ml. Results: Table 1 summarizes demographic data and laboratory results of plasma collected from donors. Plasma from 10 healthy volunteers were used as controls (8 women, median age 29 years [range 20-42]). None of the participants had an history of thrombosis. Early period CCP donors were significantly older compared to late period CCP donors, and approximately 80% of donors were male. Two donors had elevated APLA values and 5 had elevated normalized LAC SCT ratio, for a total prevalence of 6%. LAC was positive in the late period while APLA were found in the early period. All controls were negative for LAC and 9 were APLA negative. One woman had an elevated APLA anti-β2GP1 IgM (40.1 SMU u/ml).There was no association between anti-SARS-CoV-2 antibodies titer and the presence of LAC / APLA. Image:Summary/Conclusion: Our results demonstrate low frequency (6%) of APLA / LAC in plasma collected from donors who have fully recovered from mild COVID-19.The low frequency of APLA/LAC can be explained by the mild COVID-19 disease prior to plasma donation or the rapid disappearance of autoantibodies after the acute disease. The presence of LAC in the plasma of late period CCP donors and APLA in the early period donors can be explained by the changed in SARS-CoV-2 viral variants between the two time periods (wild type alpha and non-alpha variants in the early and late periods, respectively).The age of plasma donors in early CCP period was older than the age of those who donated in late period, reflecting the fact that the alpha variant was more common in elderly people during the early pandemic or that there was a careful selection of CCP donors during the course of the pandemic. The fact that convalescent donors had no thromboembolic disease at the time of plasma collection and the low prevalence of APLA/LAC in this cohort, reassures the safety of CCP use.

Apport de la détection des anticorps antiphosphatidylsérine/prothrombine (aPS/PT) dans le diagnostic et la prise en charge du syndrome des antiphospholipides (SAPL)

Antiphospholipid syndrome (APS) is an autoimmune disease and one of the most common causes of acquired thrombophilia. It is characterised by the occurrence of thrombotic or obstetric events associated with the presence of persistent antiphospholipid antibodies. The diagnosis can be challenging, particularly because some biological tests can be disturbed by anticoagulant treatment or inflammation.In the recent years, new antiphospholipid antibodies, including anti-phosphatidylserine/prothrombin antibodies (anti-PS/PT), have emerged but their clinical significance and causality remain uncertain.Biologically, several studies have found a strong correlation between the presence of lupus anticoagulant (LA) and anti-PS/PT antibodies. Clinically, the presence of anti-PS/PT antibodies is associated with an increased risk of thrombosis and obstetric complications. There is also an association with thrombocytopenia, suggesting that the presence of anti-PS/PT antibodies may be associated with more severe clinical APS. Among seronegative APS patients, 6–17% of patients are positive for anti-PS/PT antibodies. This might influence the therapeutic management of patients.This article aims to provide an update on contribution of anti-PS/PT antibodies detection for the diagnosis and management of APS.

Acquired hemophilia A in the setting of dual anticoagulation therapy and lupus anticoagulant: a case report

BackgroundAcquired hemophilia A is a disorder caused by autoantibodies against coagulation factor VIII that may present with severe bleeding. We report a rare case of acquired hemophilia A presenting with coexisting lupus anticoagulant.Case presentationAn 81-year-old Caucasian female presented with large ecchymoses over the torso and extremities in the setting of an enoxaparin bridge to warfarin. Anticoagulation was held, but she continued to develop bruises with significant anemia and prolonged coagulation studies that failed to correct with mixing. Workup revealed factor VIII activity < 1% and a positive lupus anticoagulant. Initial testing for a factor VIII inhibitor was confounded by the presence of lupus anticoagulant, requiring a chromogenic Bethesda assay to confirm the presence of the inhibitor, establishing the diagnosis of acquired hemophilia A. The patient was initially treated with oral prednisone 80 mg daily and factor VIII inhibitor bypassing activity 25 units/kg twice daily before transitioning to susoctocog alfa 50 units/kg twice daily after placement of a tunneled line for outpatient rituximab infusions. On discharge, the patient’s ecchymoses were resolving and factor VIII levels improved. Following completion of rituximab therapy, the patient’s factor VIII activity normalized and factor VIII inhibitor was suppressed.ConclusionsDiagnosis of acquired hemophilia A can be confounded by other causes of abnormal coagulation studies and may require specialized testing, such as a chromogenic Bethesda assay, to confirm the presence of a factor VIII inhibitor.

Lupus anticoagulant in patients with systemic lupus erythematosus is associated with lower E/A ratio and progressive left ventricular dilatation: a five-year follow-up study

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Copenhagen University Hospital Background Systemic lupus erythematosus (SLE) is an autoimmune disease with increased risk of cardiovascular complications such as coronary artery disease, myocarditis, pericarditis and valvular dysfunction. The pathophysiological mechanisms are poorly understood and clinical, biochemical and/or imaging markers to identify high risk patients are warranted. Purpose We aimed to identify SLE-characteristics that are associated with progressive cardiac dysfunction during a five-year follow-up period in patients with SLE. Methods A total of 147 patients with SLE were included from 2013 to 2014. All patients underwent standard echocardiography at baseline as well as a collection of blood samples, including a selection of biomarkers. Patients were invited to a five-year follow-up with a total of 108 patients (90 % female, mean age 46 ± 13 years, median disease duration of 14 (7-21) years) completing a full echocardiographic, laboratory, and clinical examination. Multivariate regression analyses with eight independent baseline variables of interest (age, sex, disease activity (SLEDAI-2K), lupus nephritis, ischemic heart disease (IHD), antiphospholipid antibodies (IgM and IgG), and lupus anticoagulant(LAC)) were performed as for the association with baseline echocardiographic parameters as well as for changes during follow-up. Only echocardiographic measurements that changed significantly (p &amp;lt; 0.01) during follow-up were selected for the regression analyses. Left ventricular end-diastolic volume index (LVEDVI) and E/A ratio were log-transformed at baseline in the regression analyses due to non-normality. Results During a five-year follow-up period, LVEDVI increased from 43.5 ± 13.9 to 52.5 ± 15.7 ml/m2 (p &amp;lt;0.001), and left ventricular diastolic measures declined (E/A ratio 1.4 ± 0.5 vs. 1.3 ± 0.5, p = 0.002; e’ velocity 12.8 ± 3.8 vs. 12.0 ± 3.7 ms, p = 0.02; mitral valve deceleration time 227.9 vs. 200.8 ms, p &amp;lt; 0.001), except for E/e’ (7.5 ± 3.8 vs. 6.8 ± 3.4, p = 0.02). Left ventricular ejection fraction remained stationary (59.5 ± 6.8 vs. 59.6 ± 6.4 %, p = 0.81). In multivariate regression analyses, presence of LAC was significantly associated with progressive left ventricular dilation during the follow-up period (p = 0.003) but not with higher baseline levels (p = 0.64) (Fig. A1 &amp; A2). LAC was associated with lower E/A ratio at baseline (p = 0.005) but did not predict a decrease of E/A ratio during follow-up (p = 0.24) (Fig. B1 &amp; B2). IHD was associated with higher LVEDVI at baseline (p = 0.004), but not with further progression of dilation (p = 0.07). Conclusion Presence of LAC was associated with lower E/A ratio at baseline as well as progressive left ventricular dilation during a five-year follow-up period. Hence, LAC might be a predictor of progressive cardiac dysfunction in patients with SLE. LAC is known to have implications for the microvascular circulation, but the clinical significance of the present findings is yet to be elucidated. Abstract Figure A Abstract Figure B

Warfarin monitoring and interference by lupus anticoagulant in patients with antiphospholipid syndrome

IntroductionPatients with antiphospholipid syndrome (APS) receive vitamin K antagonists, which warrants international normalized ratio (INR) monitoring. Research has indicated that presence of lupus anticoagulant (LA) can interfere with INR results obtained by point-of-care testing (POCT) devices. We aimed to investigate whether a systematic difference exists between POCT-INR and plasma-INR in patients with APS. Materials and methodsWe compared 291 paired POCT- and plasma-INR results from 52 LA-positive APS patients receiving warfarin with each patient having a minimum of three paired measurements of paired POCT-INR (CoaguChek, Roche Diagnostics) and plasma-INR. Agreement limits were considered satisfactory if differences were within ±0.4 INR for plasma-INR < 2.0, within ±20% for plasma-INR 2.0 to 3.5, within ±20% for plasma-INR > 3.5 to 4.5, within ±25% for plasma-INR > 4.5 to 6.0 and within ±30% for plasma-INR > 6.0. ResultsA strong positive correlation was found between POCT- and plasma-INR, Spearman's rho (95% CI) = 0.72 (0.65–0.78), p < 0.001. The average bias was 0.1 INR (3.7%), p < 0.001. 79% of paired INR results met the agreement limits with 67% of the diverging POCT-INRs being from a subset of five patients, who had consistently higher POCT- than plasma-INR. ConclusionsThe majority of LA-positive APS patients had no clinically significant difference between POCT-INR and plasma-INR. However, in a subset of patients, clinically significant systematic differences were found. Consequently, systematic comparison of a minimum three paired POCT- and plasma-INR results is recommended before implementing POCT-INR monitoring in LA-positive APS patients.

Вплив антифосфоліпідних антитіл на ризик невдалої імплантації після запліднення in vitro

Infertility is a unique pathology because it concerns a couple, not one person, and is the cause of a whole range of medical, social, demographic and economic problems. With the active development of assisted reproductive technologies, the demand for solving the problem of infertility has grown significantly. However, the prevalence of infertility remains stable, indicating many «white» spots in the diagnosis and treatment of this pathology and determining the search for new risk factors, diagnostic criteria, and treatment algorithms. Purpose — to analyze the factors that may affect implantation, namely the presence of lupus anticoagulant and antiphospholipid antibodies in women with infertility who have undergone in vitro fertilization. Materials and methods. A survey of 106 women diagnosed with infertility underwent treatment with assisted reproductive technologies in September 2019 — February 2021. The control (1) group consisted of women who received infertility treatment according to the standard scheme: controlled ovarian stimulation, gamete collection, intracytoplasmic sperm injection and embryo transfer. The main (2) group included patients who received aspirin, anticoagulants, and intravenous IgG immunoglobulins in addition to the standard treatment regimen. In the present study, levels of lupus anticoagulant and antiphospholipid antibodies were determined in both groups. Results. The study found no differences between groups of patients in levels of antibodies (AB) to phospholipids (IgG), beta-2-glycoprotein (IgG, IgM) and lupus anticoagulant (screening, confirmation) in the two groups of patients (p&gt;0.05). Difference in two groups were in levels of AB to beta-2-glycoprotein IgM in controls, on average, 9.42 units/ml (5.86 units/ml — 12.35 units/ml), and in patients of main group — 7.23 units/ml (3.14 units/ml — 10.58 units/ml), p=0.015. One-factor logistic regression models were used to clinically understand the influence of factors associated with the risk of implantation failure. The analysis did not reveal a connection between risk of implantation failure and levels of autoantibodies (aAB) to phospholipids (IgG, IgM), beta-2-glycoprotein (IgG, IgM) and lupus anticoagulant (screening, confirmation) in two groups of patients (p&gt;0.05 in all cases). Conclusions. The presence of aAB and/or antiphospholipid syndrome during the establishment of infertility factors is an essential component of the algorithm for diagnostic search for the cause of infertility and miscarriage. However, based on the obtained data, the presence of aAB in the study does not affect the implantation process nor affects the treatment of infertility. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: infertility, implantation failure, antiphospholipid syndrome, assisted reproductive technologies.

Hematological involvement in pediatric systemic lupus erythematosus: A multi-center study.

Introduction: Systemic lupus erythematosus (SLE) may present with features of several systems, including hematological manifestations. In this study, we aimed to evaluate the characteristics of hematological involvement and assess possible associations and correlations in pediatric SLE patients. Method: This is a retrospective multi-center study. The medical records of pediatric SLE patients followed between January 2000 and June 2020 were analyzed. All children fulfilled the criteria of the Systemic Lupus International Collaborating Clinics. Results: The study included 215 children with SLE, 118 of whom had hematological manifestations. Concomitant renal involvement and low C3 levels were significantly more frequent in patients with hematological involvement (p = 0.04, p = 0.008, respectively). Also, anti-cardiolipin, anti-beta-2-glycoprotein I (anti-β2 GP1), and anti-Sm antibody positivity, and the presence of lupus anticoagulant were more common in the group with hematological findings (p = 0.001 for anti-cardiolipin antibody positivity and p < 0.001 for the positivity of anti-β2 GP1 antibody, anti-Sm antibody, and lupus anticoagulant). The most common hematologic abnormality was anemia (n = 88, 74.5%), with autoimmune hemolytic anemia constituting the majority (n = 40). Corticosteroids followed by IVIG were the mainstay of treatment. In patients resistant to corticosteroid and IVIG treatments, the most preferred drug was rituximab. Low levels of C3, high SLEDAI score, high incidence of renal involvement, and positive antiphospholipid antibodies were associated with hematological involvement in the univariate analysis. The presence of antiphospholipid antibodies and high SLEDAI score were independently associated with hematological involvement in multivariate analysis (OR: 4.021; 95% CI: 2.041-7.921; p < 0.001 and OR: 1.136; 95% CI: 1.065-1.212; p < 0.001). Conclusion: Hematological abnormalities are frequently encountered in pediatric SLE. Positive antiphospholipid antibodies and high SLEDAI scores were associated with hematological involvement.

Association of Lupus Anticoagulant with Brain Atrophy in Gulf War Illness (GWI)

Separate lines of research have documented brain atrophy and evidence of autoimmune mechanisms in Gulf War Illness (GWI), including the presence of lupus anticoagulant (LAC), in veterans with GWI. Here we evaluated the possible association of LAC and brain volume in veterans with GWI. The presence of LAC was determined using Silica Clotting Time and dilute Russell’s Viper Venom Time assays. MRI data was acquired using a Philips 3T MR scanner from which total gray matter, total cortical gray matter, total subcortical gray matter, and total cerebral white matter were derived. The results demonstrated a statistically significant reduction of brain volume in all regions tested in GWI veterans with positive LAC, as compared to those without LAC. These findings add to the literature implicating autoimmune mechanisms in GWI and point to the presence of prothrombotic antiphospholipid antibodies as contributing to brain atrophy in GWI.

Deciphered coagulation profile to diagnose the antiphospholipid syndrome using artificial intelligence

The antiphospholipid syndrome (APS) is diagnosed by the presence of lupus anticoagulant and/or antibodies against cardiolipin or β2-glycoprotein-1 and the occurrence of thrombosis or pregnancy morbidity. The assessment of overall coagulation is known to differ in APS patients compared to normal subjects. The accelerated production of key factor thrombin causes a prothrombotic state in APS patients, and the reduced efficacy of the activated protein C pathway promotes this effect. Even though significant differences exist in the coagulation profile between normal controls and APS patients, it is not possible to rely on a single test result to diagnose APS. A neural network is a computing system inspired by the human brain that can be trained to distinguish between healthy subjects and patients based on subject specific data. In a first cohort of patients, we developed a neural networking that diagnoses APS. We clinically validated this neural network in a separate cohort consisting of APS patients, normal controls, controls visiting the hospital for other indications and two diseased control groups (thrombosis patients and auto-immune disease patients). The positive predictive value ranged from 62% in the hospital controls to 91% in normal controls and the negative predictive value of the neural network ranged from 86% in the thrombosis control group to 95% in the hospital controls. The sensitivity of the neural network was higher than 90% in all control groups. In conclusion, we developed a neural network that accurately diagnoses APS in the validation cohort. After further clinical validation in newly diagnosed patients, this neural network could possibly be clinically implemented to diagnose APS based on thrombin generation data.

WITHDRAWN: Hematological involvement in pediatric systemic lupus erythematosus: A multi-center study.

Introduction Systemic lupus erythematosus (SLE) may present with features of several systems, including hematological manifestations. In this study, we aimed to evaluate the characteristics of hematological involvement and assess possible associations and correlations in pediatric SLE patients. Method This is a retrospective multi-center study. The medical records of pediatric SLE patients followed between January 2000 and June 2020 were analyzed. All children fulfilled the criteria of the Systemic Lupus International Collaborating Clinics. Results The study included 215 children with SLE, 118 of whom had hematological manifestations. Concomitant renal involvement and low C3 levels were significantly more frequent in patients with hematological involvement ( p = 0.04, p = 0.008, respectively). Also, anti-cardiolipin, anti-beta-2-glycoprotein I (anti-β2 GP1), and anti-Smith (anti-Sm) antibody positivity, and the presence of lupus anticoagulant were more common in the group with hematological findings ( p = 0.001 for anti-cardiolipin antibody positivity and p &lt; 0.001 for the positivity of anti-β2 GP1 antibody, anti-Sm antibody, and lupus anticoagulant). The most common hematologic abnormality was anemia ( n = 88, 74.5%), with autoimmune hemolytic anemia constituting the majority ( n = 40). Corticosteroids followed by IVIG were the mainstay of treatment. In patients resistant to corticosteroid and IVIG treatments, the most preferred drug was rituximab. The presence of antiphospholipid antibodies and high SLEDAI score were independently associated with hematological involvement in multivariate analysis (OR: 0.249; 95%CI: 0.126–0.490; p &lt; 0.001 and OR: 1.136; 95%CI: 1.065–1.212; p &lt; 0.001). Conclusion Hematological abnormalities are frequently encountered in pediatric SLE. Positive antiphospholipid antibodies and high SLEDAI scores were associated with hematological involvement.

Correlation between activated partial thromboplastin time and diluted Russell’s viper venom time in the presence of lupus anticoagulant

Correlation between activated partial thromboplastin time and diluted Russell’s viper venom time in the presence of lupus anticoagulant

Thrombophilia testing in patients with portal vein thrombosis

Portal vein thrombosis (PVT) is a rare but severe condition. Several risk factors predispose to PVT. However, it remains unclear to which degree thrombophilia contributes to the risk of PVT and whether PVT patients should be routinely referred for thrombophilia testing. The aim of the present study was to investigate the prevalence of thrombophilia in PVT patients to clarify the relevance of thrombophilia testing in PVT patients. Clinical data and results from thrombophilia investigations were systematically obtained from all PVT patients referred to Centre for Hemophilia and Thrombosis, Aarhus University Hospital, Denmark for thrombophilia testing between 1st of January 2010 and 31st of December 2018 (n = 93). The investigated thrombophilias included factor V Leiden and prothrombin G20210A mutations, deficiency of protein S, protein C and antithrombin, antiphospholipid syndrome, and increased levels of factor VIII. The prevalence of thrombophilia was compared to healthy controls obtained from previously published data on thrombophilia distribution in cohorts of the Western European adult general population. Comparing PVT patients with healthy controls, significantly increased odds of presence of lupus anticoagulant (crude odds ratio (OR) 6.2, 95% confidence interval (CI) 1.8–20.6) were found, whereas no significantly increased odds of inherited thrombophilia were demonstrated. In conclusion, routine testing for inherited thrombophilia in PVT patients does not seem indicated. However, PVT patients should still be tested for antiphospholipid antibodies because patients meeting the criteria for antiphospholipid syndrome preferentially should receive vitamin K antagonists as anticoagulant therapy.

The clinical and serological associations of hypocomplementemia in a longitudinal sle cohort

BackgroundIn SLE, low complement is an important serological manifestation. Recent classification criteria include hypocomplementemia and one gives additional weight if both C3 and C4 are low. We evaluated patients with a history of, and those with persistently, low complement. As complement activation occurs in the antiphospholipid antibody syndrome, an analysis was also performed on those with positive antiphospholipid antibodies to evaluate thrombotic outcomes. MethodsIn a longitudinal SLE cohort, organ manifestations, damage, C3, C4 and antiphospholipid antibodies were assessed quarterly. Using univariate and multivariate methods we compared those with and without a history of low C3, low C4 and both. We evaluated those who had a history of low complement at any time point, and those who had persistent hypocomplementemia. Further analysis considered thrombotic outcomes in patients with positive antiphospholipid antibodies and a history of low complement. Results2399 patients were evaluated. Fifty-five percent had a history of low C3 and 47% low C4; 83 (4%) had persistently low C3 and 65 (3.2%) had persistently low C4. Hematological, renal and serological abnormalities associated with a history of low C3 but not low C4. With anticardiolipin antibodies, a history of hypocomplementemia (both C3 and C4 low) associated with stroke and deep venous thrombosis. ConclusionLow C4 was a weak marker in terms of the associated clinical and serological manifestations. Low C3 associated with renal involvement and poor renal outcomes. A history of both low C3 and C4 associated with stroke in the presence of lupus anticoagulant or anticardiolipin antibodies, and low C4 with digital gangrene (with lupus anticoagulant).

Cutaneous Complications Secondary to Haemostasis Abnormalities in COVID-19 Infection.

We describe the case of a patient hospitalized for acute decompensated heart failure in a standard medical ward. During hospitalization, he was diagnosed with COVID-19 and transferred to a special unit. The clinical course was marked by worsening of the respiratory disease, the development of right parotiditis and thrombosis of the left internal jugular vein. Therapeutic anticoagulation was initiated and 2 days later, the minimal dermatoporosis lesions previously present in the upper extremities evolved to haemorrhagic bullae with intra-bullae blood clots and dissecting haematomas. Surgical management of the dissecting haematomas was difficult in the context of haemostasis abnormalities. The patient died 29 days after hospital admission.LEARNING POINTSSingle room accommodation should be preferred to double room accommodation in standard wards during the COVID-19 pandemic.Anticoagulation therapy and the presence of lupus anticoagulant may induce cutaneous complications during COVID-19 infection.The discontinuation of anticoagulation therapy did not help improve the management of cutaneous lesions.