scholarly journals Increased thrombin generation and activity in patients with systemic lupus erythematosus and anticardiolipin antibodies: evidence for a prothrombotic state [see comments]

Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 2958-2963
Author(s):  
JS Ginsberg ◽  
C Demers ◽  
P Brill-Edwards ◽  
M Johnston ◽  
R Bona ◽  
...  

The objective of this study is to determine whether patients with systemic lupus erythematosus (SLE) and anticardiolipin antibodies (ACA) have biochemical evidence of an ongoing prothrombotic state. Using a cross-sectional analysis of a cohort design in an outpatient SLE clinic setting, 43 consecutive patients with SLE participated. Patients underwent clinical and laboratory evaluations on two separate occasions at least 3 months apart. As part of the clinical evaluation, the following were ascertained: (1) the ongoing use of warfarin therapy; (2) the presence of prior venous and arterial thromboembolic disease by history, critical review of objective tests, and examination for reflux in the deep veins of the legs as an indicator of venous thrombosis; and (3) disease-related activity by performing a lupus activity criteria count (LACC). As part of the laboratory evaluation, blood was taken on both occasions and assayed for prothrombin fragments (F1 + 2) and fibrinopeptide A (FPA), as indices of thrombin generation and activity, respectively, and ACA. For the analyses, patients were classified as ACA+ if the assay was abnormal on both occasions and ACA- if the assay was negative on both occasions or negative on one occasion and positive on the other. ACA+ patients had: (1) a significantly higher mean level of F1 + 2 (1.07 nmol/L) than ACA- patients (0.79 nmol/L; P = .02) and patients receiving warfarin (0.47 nmol/L; P = .009) and (2) a significantly higher mean level of FPA (1.01 nmol/L) than ACA- patients (0.45 nmol/L; P = .02). When patients with prior thromboembolism were excluded from the analysis, significant differences in the mean levels of F1 + 2 and FPA between ACA+ and ACA- patients were still seen, whereas when patients with prior thromboembolism and/or active disease were excluded from the analysis, a significant difference in the mean level of FPA and a nonsignificant trend in the mean level of F1 + 2 were seen. The results of this study support the hypothesis that the presence of ACA in SLE patients is associated with an ongoing prothrombotic state.

Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 2958-2963 ◽  
Author(s):  
JS Ginsberg ◽  
C Demers ◽  
P Brill-Edwards ◽  
M Johnston ◽  
R Bona ◽  
...  

Abstract The objective of this study is to determine whether patients with systemic lupus erythematosus (SLE) and anticardiolipin antibodies (ACA) have biochemical evidence of an ongoing prothrombotic state. Using a cross-sectional analysis of a cohort design in an outpatient SLE clinic setting, 43 consecutive patients with SLE participated. Patients underwent clinical and laboratory evaluations on two separate occasions at least 3 months apart. As part of the clinical evaluation, the following were ascertained: (1) the ongoing use of warfarin therapy; (2) the presence of prior venous and arterial thromboembolic disease by history, critical review of objective tests, and examination for reflux in the deep veins of the legs as an indicator of venous thrombosis; and (3) disease-related activity by performing a lupus activity criteria count (LACC). As part of the laboratory evaluation, blood was taken on both occasions and assayed for prothrombin fragments (F1 + 2) and fibrinopeptide A (FPA), as indices of thrombin generation and activity, respectively, and ACA. For the analyses, patients were classified as ACA+ if the assay was abnormal on both occasions and ACA- if the assay was negative on both occasions or negative on one occasion and positive on the other. ACA+ patients had: (1) a significantly higher mean level of F1 + 2 (1.07 nmol/L) than ACA- patients (0.79 nmol/L; P = .02) and patients receiving warfarin (0.47 nmol/L; P = .009) and (2) a significantly higher mean level of FPA (1.01 nmol/L) than ACA- patients (0.45 nmol/L; P = .02). When patients with prior thromboembolism were excluded from the analysis, significant differences in the mean levels of F1 + 2 and FPA between ACA+ and ACA- patients were still seen, whereas when patients with prior thromboembolism and/or active disease were excluded from the analysis, a significant difference in the mean level of FPA and a nonsignificant trend in the mean level of F1 + 2 were seen. The results of this study support the hypothesis that the presence of ACA in SLE patients is associated with an ongoing prothrombotic state.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_5) ◽  
Author(s):  
O Gacem ◽  
L Labboun ◽  
N Mansouri ◽  
M Gherbi ◽  
Z Zeroual ◽  
...  

Abstract Background Pediatric Systemic Lupus Erythematosus (pSLE) is a chronic mutisystemic autoimmune disease with complex clinical manifestations whose diagnosis is not always easy and the course is generally severe and the treatment is not very well codified and often extrapolated from that of adults. This study aims to describe the clinical, immunological, therapeutic characteristics and short outcome of systemic lupus erythematosus in Algerian children. Methods This was a prospective, multicentre and descriptive study 36 months (January 2015 - December 2018) at the department of Pediatrics of University Hospital Nefissa Hamoud ex Parnet Algiers. Children less than16 years of age fulfilling the American College of Rheumatology SLE criteria were included. Disease activity estimated by Systemic Lupus Erythematosus Disease Activity index (SLEDAI) whose use has been validated in children and damage index based on Systemic Lupus International Collaborating Clinics (SLICC) score were determined. Results Eighty-three (83) patients were studied. Female: male ratio was1:49. Mean ages at lupus onset and diagnosis were respectively: 10, 12 ± 3, 88 and 11, 3 ± 3, 62 years. All patients had skin involvement while constitutional signs including fever and asthenia were observed in (98.8%). Rheumatological, renal, neuropsychiatric, cardiac, hepato-digestive, pleuropulmonary and ocular disorders were observed respectively: 65, 1%, 44, 6%, 41%, 27, 7%, 41%, 19, 3% and 7, 2%. All patients were positive for antinuclear antibodies. Anti-double-stranded DNA (75%) was the most frequently observed autoantibody profile. Antiphospholipid antibody positivity was noted in 52% whereas hypocomplementemia in fractions C3, C4 was observed in 55% and 56% respectively. In our study, the severe forms were more frequent (83%) than the mild ones (17%) with a significant difference (P = < 10–6). Overall, the mean SLEDAI at disease onset was 22.11 ± 11.87 with high activity ≥ 20 in 59% of cases. The mean damage score was 1.8 ± 2.045 (interquartile range 0–8). Among induction drugs, oral corticosteroids were the most frequently used (92%), and in a third of cases intravenously at high doses in combination with immunosuppressive therapy. In induction therapy, cyclophosphamide (CYC) was the most used drug (23%) compared with mycophenolate mofetil (MMF) (14%). Unlike the maintenance phase where MMF observed an increase (28%) vs (8%) CYC. The use of MMF was correlated with severe lupus nephritis with a significantly effective difference in the decrease in SLEDAI (P = 0.0001). The use of hydroxychloroquine (HCQ) was observed in 81% in induction and 89% in maintenance treatment. The correlation of HCQ use with survival was significantly positive (P = 0.04). Indeed, adherence to treatments and essentially HCQ was a protective factor, its odds ratio is < 1 with a significant p-value, [OR 0.016 95% CI (0.001–0.353)]. Mortality was estimated at 11%. Multivariable regression analysis showed that the neurological involvement (odds ratio = 6,093 95% confidence interval ((1,1 8 0 ∼ 31 446)) and macrophage activation syndrome were associated with a high risk of mortality. Conclusion we report a series of pSLE characterized by great clinical and biological heterogeneity. It follows a severe course of the disease with high disease activity at the diagnosis and therefore leads to high morbidity and mortality. However, these results must be confirmed by other pediatric studies which could form the basis of a diagnostic and therapeutic approach more adapted for children. Keywords Algeria, Child, Clinical features, Disease activity, lupus


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2317-2317
Author(s):  
Ihosvany Fernandez Bello ◽  
Francisco Javier López Longo ◽  
Victor Jiménez Yuste ◽  
Miguel Canales ◽  
Juan Ovalles ◽  
...  

Abstract Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disorder of unknown origin with a high mortality pattern due to the development of a premature cardiovascular disease. The presence in these patients of a dysfunctional endothelium together with a hypercoagulable milieu may contribute to an increased incidence of thrombotic events. Increased thrombin generation, elevated levels of circulating microparticles and plasmatic levels of PAI-1 may contribute to the prothrombotic phenotype of the disease but data are scarce. Objectives: 1-To characterize the prothrombotic state in SLE by rotational thromboelastometry (ROTEM) and thrombin generation linked to tissue factor bearing microparticles. 2- To evaluate endothelial damage in patients with SLE and its relationship with the prothrombotic state of the disease. 3- To evaluate the influence of PAI-1 in the prothrombotic state of SLE. Material and methods: 39 patients with SLE and 25 sex and age matched healthy subjects were included. Whole blood was drawn in standard BD sodium citrate tubes (3.2%). ROTEM was performed in naTEM condition. Clotting time (CT, time from start of measurement until initiation of clotting [in seconds], alpha angle, which reflects the rate of fibrin polymerisation (tangent to the curve at 2-mm amplitude [in degrees]), maximum clot firmness, which reflects the maximum tensile strength of the thrombus (MCF, [in mm]), the time that clot takes to increase from 2mm above baseline to 20mm above baseline (CFT) and A5, amplitude at 5 min, were recorded. To evaluate the presence of tissue factor bearing microparticles, thrombin generation was determined by Calibrated Automated Thrombogram (CAT) in presence of 4 mM phospholipid (MP-Reagent, Diagnostica Stago, Spain). The endogenous thrombin potential (ETP, the total amount of thrombin generated over time); the lag time (the time to the beginning of the explosive burst of thrombin generation); the peak height of the curve (the maximum thrombin concentration produced); and the time to the peak were evaluated. Antigenic levels of E-selectin and PAI-1 were determined by ELISA (R&D Systems, MN, USA and Affymetrix eBioscience, Vienna, Austria) respectively. Results: ROTEM parameters showed a hypercoagulable profile in LES patients. CT and CFT were shorter (p<0.001 in both cases), and MCF, alpha angle and A5 were higher (p<0.001, p<0.02 and p<0.001 respectively) when compared to healthy controls. On the other hand, CAT parameters did not show differences between both groups. Nevertheless, in LES patients but not in controls, CAT parameters significantly correlated with ROTEM ones (Table 1). Table 1.Correlations in the LES patients group between CAT and ROTEM parameters. Analyses were performed with Spearman test. N: number of determinations; p* denotes significance.CTCFTMCFMCF-talphaA5A10ETP(MP)r-,301-,375*,369*-,368*,378*,364*,393*p,0840,028*0,031*0,032*0,027*0,034*0,021*N34343434343434Peak(MP)r-,353*-,396*,372*-,345*,396*,393*,402*p0,040*0,020*0,030*0,045*0,020*0,021*0,018*N34343434343434ttPeak(MP)r,240,222-,242,217-,223-,209-,210p,171,207,168,217,205,236,232N34343434343434 In order to evaluate endothelial damage, plasma E-selectin and PAI-1 were determined. No differences were found in E-selectin level whereas increased PAI-1 levels were seen in LES group (p<0.006). PAI-1 did not correlate to ROTEM parameters. Conclusions: ROTEM can detect a hypercoagulable state in patients with SLE. The hypercoagulable state may be linked to increased tissue factor bearing microparticles and increased PAI-1 plasma levels. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1141-1141
Author(s):  
Elena Monzón Manzano ◽  
Ihosvany Fernandez-Bello ◽  
Raul Justo Sanz ◽  
Larissa Valor ◽  
Francisco Javier López-Longo ◽  
...  

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin characterized by a hypercoagulable state and a high mortality rate. Mechanisms that cause the accelerated deterioration of cardiovascular health in SLE are unknown. Objectives: to characterize the prothrombotic state in SLE patients by global coagulation assays and the contribution of platelets, endothelial damage, microparticles and neutrophil extracellular traps (NETs) in their prothombotic profile. Material and methods: 72 patients and 90 healthy controls were recruited. Patients were classified according to clinical characteristics in: 32 with lupus (SLE group), 29 with SLE and antiphospholipid antibodies (aFL, SLE+aFL group) and 12 who met the criteria for SLE and antiphospholipid syndrome (APS, SLE+APS group). Experimental protocol was approved by La Paz University Hospital Ethics Committee. Venous blood collected in BD sodium citrate tubes (3.2%) was centrifuged at 150 g for 20 min at 23ºC to obtain platelet-rich plasma (PRP). PPP was obtained by centrifugation at 1500 g for 15 min at 23ºC. To obtain neutrophils, whole blood was centrifuged to 1600 rpm 25 min using a Ficoll gradient and red cells were lysed. Rotational thromboelastometry (ROTEM®) was performed in naTEM condition. Clotting time (CT, time from start of measurement until initiation of clotting [in seconds]); alpha angle (tangent to the curve at 2-mm amplitude [in degrees]), Ax (clot firmness at time x, [in mm]) and maximum clot firmness (MCF, [in mm]) were recorded. Procoagulant activity associated to microparticle's content of tissue factor was determined in PPP by Calibrated Automated Thrombogram (CAT) using MP-reagent (4 mM phospholipids, Diagnostica Stago, Spain). We evaluated the endogenous thrombin potential (ETP, the total amount of thrombin generated over time); the lag time (the time to the beginning of the explosive burst of thrombin generation); the peak height of the curve (the maximum thrombin concentration produced) and the time to the peak. Thrombin generation associated to NETs was also measured by CAT. Neutrophils from healthy controls or from LES patients were stimulated with 100 nM PMA in RPMI medium during 45 min at 37º and then cocultivated with PRP adjusted to 105 platelets/µL. NETs formation was verified by fluorescent microscopy performed with DAPI and an anti-myeloperoxidase antibody. Plasma levels of LDL-ox, E-Selectin and PAI-1 were determined by Elisa (R&D Systems, MN, USA and Affymetrix eBioscience, Vienna, Austria, respectively). Platelet activation was analysed by flow cytometry (FCM, FACScan, BD Biosciences). Fibrinogen receptor activation was evaluated through PAC1-FITC binding and release of granule's content was assessed with monoclonal antibodies (mAbs) anti-CD63 and anti P-selectin in quiescent and 100 µM TRAP and 10 µM ADP stimulated platelets. Data were analysed with Graphpad prism and p ≤0.05 was stablished as statistical significance. Results: PAI-1 plasma level was increased in all patient's groups, whereas LDL-ox and E-selectin showed no differences with control cohort (Fig.1). ROTEM demonstrated a procoagulant profile in SLE and SLE+aPL but not in SLE+APS group (Fig. 2). PAI-1 levels correlated with several ROTEM parameters (Table 1). SLE patients and SLE+aFL showed a basal platelet activation. Moreover, SLE group exposed more P-selectin and CD63 than controls (Fig.3). Regarding thrombin generation associated to tissue-factor content of microparticles, no differences were observed between SLE patients and healthy controls. On the other hand, SLE patients had an increased peak of thrombin generation related to NETs formation (control group: 170.3± 58.0, SLE patients: 230.6±39.3, p=0.019). Conclusions: ROTEM® detected a hypercoagulable state in SLE and SLE+aPL patients. The hypercoagulable state might be linked to increased PAI-1 plasma levels and basal platelet activation in SLE and SLE+aPL groups. Moreover, neutrophils from SLE patients seemed to present a basal activation that induced a NETs-related procoagulant state in these patients. SLE+APS patients did not show a hypercoagulable state perhaps because of the presence of lupus anticoagulant and/or to therapeutic treatment of these patients. This work was supported by grants from the FIS-FONDOS FEDER (PI15/01457, NB). NVB holds a Miguel Servet tenure track grant from FIS-FONDOS FEDER (CP14/00024). Disclosures Fernandez-Bello: Novartis, Pfizer, ROCHE, Stago: Speakers Bureau. Robles:ABBVIE, SANDOZ FARMACEUTICA: Speakers Bureau. Álvarez Roman:Sobi: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Research Funding; NovoNordisk: Consultancy, Speakers Bureau. Canales:Celgene: Honoraria; Gilead: Honoraria; Novartis: Honoraria; Janssen: Honoraria, Speakers Bureau; Sandoz: Honoraria; iQone: Honoraria; Takeda: Speakers Bureau; SOBI: Research Funding; Karyopharm: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau. Jimenez-Yuste:Bayer, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Sobi, Shire: Consultancy, Honoraria, Other: reimbursement for attending symposia/congresses , Research Funding, Speakers Bureau. Butta:Novartis: Consultancy; Roche, Pfizer: Speakers Bureau.


BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e038091
Author(s):  
Qiuyi Wang ◽  
Lunfang Xie ◽  
Lei Wang ◽  
Xing Li ◽  
Liangmei Xu ◽  
...  

ObjectivesTo assess the readability of printed education materials (PEMs) for patients with systemic lupus erythematosus (SLE) and to explore the perceptions of patients with SLE with different health literacy regarding the readability of PEMs.DesignA mixed-methods study, including a cross-sectional survey and semistructured interviews.SettingThe SLE PEMs were collected from 13 hospitals in China. The interviews were conducted in the Department of Rheumatology of a hospital in Hefei, China.ParticipantsIn the cross-sectional survey, convenience sampling was used to select the Chinese SLE PEMs, with 20 PEMs included. In the qualitative study, the patients with SLE were divided into two groups based on their health literacy. Then, purposive sampling was used to select participants in each group, with 18 patients recruited.Outcome measuresThe readability of PEMs was assessed by the language analysis technology and the Chinese version of the Suitability Assessment of Materials (SAM-C) instrument.ResultsFor text factors of readability, the mean Chinese language difficulty coefficient was 67.09±8.03, which indicates that the text of PEMs was difficult to read. For non-text factors, the mean SAM-C score was 45.62±9.51. Eight PEMs were rated not suitable, 12 were adequate and none were superior. In the interviews, eight categories were identified: information source, content, actionability, plain language, pictures, tables, numbers and layout. Patients with different health literacy had discrepant views on the detail of basic information, the necessity of question list, the location of functional pictures and the application of mathematical symbols.ConclusionsThe readability of Chinese SLE PEMs does not perform well, and it is necessary to reduce the difficulty of words, shorten the length of sentences and improve the picture design and actionability. To develop PEMs tailored to patients’ level of health literacy, patients’ unique view of readability should be integrated into the design of PEMs.


2022 ◽  
Vol 24 (1) ◽  
Author(s):  
Hiromi Shimada ◽  
Risa Wakiya ◽  
Kenji Kanenishi ◽  
Nobuyuki Miyatake ◽  
Shusaku Nakashima ◽  
...  

Abstract Background This study aimed to investigate the effect of glucocorticoid doses on adverse pregnancy outcomes (APOs) in women complicated by systemic lupus erythematosus (SLE). Methods We investigated 74 pregnancies complicated by SLE or SLE-dominant mixed connective tissue disease. The pregnancies were managed from conception to delivery in our institution. We retrospectively evaluated whether the mean glucocorticoid dose during pregnancy is associated with APOs, including preterm birth (PB), low birth weight (LBW), and light-for-date (LFD). We also calculated the cut-off dose of glucocorticoid that affected APOs. Results All APOs occurred in 35 (50.7%) patients, with 14 cases of PB, 23 cases of LBW, and 10 cases of LFD. Patients with all APOs or PB had a higher dose of glucocorticoid during pregnancy than patients without all APOs or with full-term birth (P = 0.03, P <  0.01, respectively). Logistic regression analysis for all APOs and PB showed that the cut-off values of the mean glucocorticoid dose were 6.5 and 10.0 mg/day, respectively. Patients who delivered LBW or LFD newborns showed no significant difference in the glucocorticoid dose used during pregnancy than patients without LBW or LFD newborns. Patients who delivered LBW newborns were more likely to have used glucocorticoids during pregnancy (P <  0.01). Conclusions In pregnancies complicated by SLE, a relatively lower dose of glucocorticoid than previously reported is significantly related to APOs, especially PB. Therefore, the disease activity of patients with SLE should be managed with the appropriate lower dose of glucocorticoid during pregnancy.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 355.2-356
Author(s):  
F. Cacciapaglia ◽  
A. Manfredi ◽  
G. Erre ◽  
E. Bartoloni Bocci ◽  
G. Sakellariou ◽  
...  

Background:Systemic lupus erythematosus (SLE) patients are at high risk for CV events, and EULAR recommends assessing the 10-year CV-risk using the Systematic Coronary Risk Evaluation (SCORE) [1]. The QRISK3, another score to assess CV-risk in UK population, considers different factors among which also SLE. The Progetto Cuore score (PCS) is validated to estimate CV risk in Italian people and largely replicates the SCORE project [2].Objectives:This cross-sectional study aimed to estimate CV-risk using SCORE, QRISK3 and, for the first time, PCS in a multicentric cohort of Italian SLE patients.Methods:During 2019 we evaluated 173 SLE patients (87.7% female; age 40±16 years; disease duration 138±105 months), fulfilling the 1997 ACR classification criteria. Clinical and laboratory data were registered, and individual CV-risk was calculated using suitable algorithms for the SCORE, QRISK3 and PCS. Statistical analysis was performed using Graphpad Instat 8.0 (San Diego, CA-USA).Results:In 13 (7%) SLE patients a previous CV event was recorded. Hypertension was present in 60 (37.5%) and diabetes in 27 (16.9%) patients. Mean total cholesterol was 184±39 mg/dL, HDLc 58±18 mg/dL, LDLc 124±37 mg/dL, triglycerides 105±63 mg/dL; dyslipidaemia was reported in 58 (36.2%) patients and 29 (18.1%) were on statin. Mean BMI was 24.9±5.3 Kg/sm, 60 (37.5%) and 23 (14.3%) patients were overweight and obese, while 25 (15.6%) patients were smokers. 87 (54.3%) SLE patients had a SLEDAI<4, 91% of patients were taken HCQ and 65% were on prednisone (mean dose 5.4±5.9 mg/day), but only 7.5% took >7.5 mg/day. The CV-risk of SLE patients according to SCORE, QRISK3 and PCS was 1.1±2.1%, 10.5±12.3% and 3.7±5.4%, respectively. Stratifying patients at low, moderate or high CV risk according to the PCS and SCORE a double proportion of patients was at moderate (8% vs 3.9%) or high (1.9% vs 0.9%) CV risk (p=0.03). Finally, CV-risk according to QRISK3 was higher than 20% (high risk) in 32/160 (20%) patients.Conclusion:This multicentre study demonstrated that the mean estimated CV-risk in SLE patients is globally low using the SCORE, QRISK3 and PCS. The PCS seems to better intercept those patients at moderate/high risk, at least in Italian SLE patients, while QRISK3 predicts the highest CV risk. The lack of disease-specific CV-risk factors (such as autoantibodies profile or organ involvement) probably account for the underestimation of CV risk using the SCORE and PCS.References:[1]ARD 2019;78(6):736-745.[2]ARD 2019;0:1–2.doi:10.1136/annrheumdis-2019-215715Disclosure of Interests:Fabio Cacciapaglia Speakers bureau: BMS; Roche; Pfizer; Abbvie, Andreina Manfredi: None declared, Gianluca Erre: None declared, Elena Bartoloni Bocci: None declared, Garifallia Sakellariou Speakers bureau: Abbvie, Novartis, MSD, Ombretta Viapiana: None declared, Sergio Colella: None declared, Anna Abbruzzese: None declared, Marco Fornaro: None declared, Giacomo Cafaro: None declared, Maria Antonietta Fenu: None declared, Bianca Lucia Palermo: None declared, Martina Dessì: None declared, Adalgisa Palermo: None declared, Alessandro Giollo: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Fabiola Atzeni: None declared, Matteo Piga: None declared


2018 ◽  
Vol 6 (8) ◽  
pp. 1323-1327 ◽  
Author(s):  
Blondina Marpaung ◽  
Andi Raga Ginting ◽  
OK Moehad Sjah

BACKGROUND: Midkine (MK) induces inflammation and could inhibit inducible regulatory T cell differentiation. These reports suggest that MK may play a role in the pathogenesis of autoimmune disease including SLE, but data about MK in SLE patients was still limited, and the role of Midkine in SLE is largely unknown.AIM: The purpose of this study was to compare serum level MK in SLE patients and control, also analysed the relationship between the serum MK level and disease activity in SLE.METHODS: This cross-sectional study was conducted in Adam Malik Hospital from January-June 2017. Diagnosis of SLE was established according to the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, and disease activity was assessed using the Mexican Systemic lupus erythematosus disease activity index (MEX-SLEDAI). Subjects with evidence of malignancy and systemic disease (pulmonary, kidney, liver, metabolic disorder, etc.) were excluded. Data analysis was performed using SPSS 22nd version. P < 0.05 was considered statistically significant.RESULTS: There were 90 subjects and divided into 2 groups: SLE patients group (n=40) and healthy control groups (n = 50). Midkine levels were increased in the serum of SLE patients compared by health control. There was a significant difference in the median serum Midkine levels between SLE patients and healthy control (P < 0.001). Elevated Midkine serum levels were a significant difference between active disease and remission (P = 0.018).CONCLUSION: Elevated Midkine serum level could be a marker of SLE disease activity and have a role in the pathogenesis of SLE.


1991 ◽  
Vol 66 (05) ◽  
pp. 520-524 ◽  
Author(s):  
A A Long ◽  
J S Ginsberg ◽  
P Brill-Edwards ◽  
M Johnston ◽  
C Turner ◽  
...  

SummaryIn order to determine whether an association exists between antiphospholipid antibodies (APLA) and thromboembolic events in patients with systemic lupus erythematosus (SLE), we performed a cross-sectional study of consecutive unselected SLE patients. The occurrence of previous thromboembolic events was determined by investigators blinded to the APLA status of the patients by critical review of objective tests that had been performed at the time of symptomatic presentation and by performing venous Doppler ultrasound of the legs to elicit venous reflux as an indication of previous venous thrombosis. The presence of APLA was determined by coagulation assays for the lupus anticoagulant (LA) using five tests with well-defined control ranges and by ELISA assay for anticardiolipin antibodies (ACLA). These tests were measured on two separate occasions. The results of the study demonstrate a statistically significant association between persistently abnormal ACLA assays and thromboembolic events and a non-significant trend between persistently abnormal LA and thromboembolic events. Transient abnormalities of LA and ACLA were less strongly associated with thromboembolic events. We conclude that in patients with SLE, there is a significant association between thromboembolism and APLA.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 353.2-354
Author(s):  
J. Birt ◽  
M. Hadi ◽  
N. Sargalo ◽  
E. Brookes ◽  
P. Swinburn ◽  
...  

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory condition impacting multiple organ systems.1,2SLE affects approximately 1.5 million Americans, disproportionately females of reproductive age, and is more prevalent in non-Caucasian populations.3Fatigue and pain are some of the most prominent symptoms of SLE, contributing to the heavy disease burden and disruption to daily life.4This study aimed to further understand the burden of SLE. Lilly worked with the Lupus Foundation of America (LFA) and Evidera to develop the SLE-UPDATE (Understanding Preferences, Disease Activity and Treatment Expectations) survey.Objectives:To understand the patient-perceived symptom burden of SLE, in particular pain and fatigue, within the current landscape of therapeutic options. This study also focused on current treatment patterns in SLE patients.Methods:This was a cross-sectional, non-interventional, online survey study conducted in partnership with the LFA. English-speaking United States patients aged ≥18 years with a self-reported diagnosis of SLE completed the survey following online screening and informed consent. Descriptive data are presented by means (standard deviation [SD]) for continuous measures, and frequency (n, %) for dichotomous measures. Demographic, clinical, and patient-reported outcomes were collected including the FACIT-Fatigue (range 0-52, higher scores indicate less fatigue), Pain Numerical Rating Scale (NRS) (0 [none] to 10 [worst imaginable]), Worst Joint Pain NRS (0 [none] to 10 [worst imaginable]), and the LupusPRO, a validated, lupus-specific quality of life (QoL) instrument (range 0-100, higher scores indicate better QoL).Results:A total of 500 patients with SLE completed the survey. Patients were predominantly female (75%), white/Caucasian (76%), with a mean age of 42.6 years and mean disease duration of 11.1 years.Most patients with SLE rated their overall condition as either good (38%) or fair (31%), with 8% rating poor and 7% excellent. Current non-biologic prescription medication use included: antimalarials 42%, corticosteroids 33%, immunosuppressants 33%, nonsteroidal anti-inflammatory drugs (NSAID) 32%, other analgesics 15% and 10% were using tofacitinib. Biologic therapies were being used by only 19%, including intravenous (IV) Benlysta (37%),subcutaneous(SC) Benlysta (25%), rituximab (17%), and 22% were using other biologics. Fatigue was the most commonly reported symptom (69%), with 40% of patients ranking fatigue as their most bothersome SLE symptom. Forty eight percent of patients with current fatigue rated the severity as moderate and 33% as severe. The mean (SD) FACIT-Fatigue score was 22.9 (12.0). The next most commonly reported symptoms were joint stiffness (57%), sleep problems (55%), joint pain/swelling (53%), and muscle pain (52%). Sixty percent of patients reported experiencing pain all or most of the time over the past seven days. A total of 30% of patients with current joint pain/swelling rated it as severe, and 24% of patients with current joint stiffness rated it as severe. The mean scores for Worst pain NRS and Worst Joint Pain NRS were both 5.8 out of 10.The LupusPRO domains indicated by respondents as the most impacted by SLE were Emotional Health, Pain/Vitality, and Lupus Medications.Conclusion:Fatigue, followed by pain and joint stiffness, were the most common patient-reported symptoms contributing to the overall SLE disease burden. Further research could highlight the efforts required to address the inadequacies in treatment and management of pain and fatigue in this patient population.Disclosure of Interests:Julie Birt Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Monica Hadi: None declared, Nashmel Sargalo: None declared, Ella Brookes: None declared, Paul Swinburn: None declared, Leslie Hanrahan: None declared, Karin Tse: None declared, Natalia Bello Vega Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Kirstin Griffing Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Maria Silk Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Laure Delbecque Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Diane L Kamen Consultant of: Consulted on SLE survey development for Lilly and consulted on SLE trial protocol development for EMD Serono in 2019


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