Thrombosis In Systemic Lupus Erythematosus Research Articles

Systemic lupus erythematosus and antiphospholipid syndrome: past, present, future

Immune-inflammatory (autoimmune and autoinflammatory) rheumatic diseases are widespread severe chronic inflammatory diseases and also "models" for studying the fundamental mechanisms of pathogenesis and approach to pharmacotherapy of other diseases associated with autoimmunity and/or autoinflammation. Uncontrolled inflammation leading to hypercoagulation forms the basis of "thromboinflammation", which is considered a universal pathogenetic mechanism of organ involvement in immune-inflammatory rheumatic diseases, as well as in COVID-19 and atherosclerotic vascular lesions (atherothrombosis). Thrombo-inflammatory mechanisms play a crucial role in systemic lupus erythematosus and antiphospholipid syndrome. Russian rheumatology, under the leadership of academician Valentina Alexandrovna Nasonova, greatly contributed to the research of these disorders. This article addresses the current view about the overlapping pathogenetic mechanisms of thrombosis in systemic lupus erythematosus and antiphospholipid syndrome, the relevance of these studies during the COVID-19 pandemic, and the prospects for antithrombotic and anti-inflammatory therapy.

Serum salusin-β levels in patients with systemic lupus erythematosus.

Endothelial dysfunction (ED) has an important role in the pathogenesis of systemic lupus erythematosus (SLE). Studies on other inflammatory diseases show that salusin-β with various mechanisms may play a role in the promotion of ED and inflammation. The aim of this study was to measure serum salusin-β levels in SLE patients and evaluate it as a potential biomarker in assessing SLE activity and predicting organ involvement. In a cross-sectional study, 60 patients diagnosed with SLE and 30 age- and sex-matched healthy controls were enrolled. Disease activity of SLE patients was assessed by the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K). Serum levels of salusin-ß were measured using a human salusin-ß enzyme-linked immunosorbent assay kit. Serum salusin-β levels in SLE and control groups were 474.2 ± 117.1pg/ml and 157.7 ± 88.7pg/ml, respectively. The difference was significant (P = 0.001). There was no significant correlation between serum salusin-β levels with age (r = - 0.06, P = 0.632) and SLEDAI (r = - 0.185, P = 0.158). In patients with nephritis and thrombosis, serum salusin-β was significantly higher. In addition, in patients with serositis, serum salusin-β was significantly lower. Multiple linear regression analysis showed that serum salusin-β levels retained a significant association with nephritis and thrombosis after model adjustment for serositis, nephritis, and thrombosis. Our findings showed that salusin-β might have a possible role in the pathogenesis of SLE. Salusin-β may be a potential biomarker for nephritis and thrombosis in SLE. Key Points • Serum salusin-β levels were significantly higher in SLE patients than the control group. • There was no significant correlation between serum salusin-β levels with age and SLEDAI. • Serum salusin-β levels retained a significant association with nephritis and thrombosis.

Antiphospholipid antibodies are persistently positive at high titers. Additive value of platelet-bound C4d.

BackgroundClassification criteria for antiphospholipid syndrome (APS) require that antiphospholipid antibody (aPL) positivity is confirmed after at least 12 weeks. We tested the hypothesis that aPL at high titers remain positive while low titers fluctuate over time. As both platelet-bound C4d (PC4d) and aPL are associated with thrombosis in systemic lupus erythematosus (SLE), we also evaluated whether PC4d can aid in APS diagnosis.MethodsData from serum or plasma sent to Exagen’s laboratory for routine aPL testing were analyzed. Anti-cardiolipin (aCL) and anti-beta2 glycoprotein-1 antibodies (aB2GP1) were measured by chemiluminescence or ELiA fluorescence enzyme immunoassay; anti-phosphatidylserine/prothrombin complex antibodies (aPS/PT) by ELISA; PC4d by flow cytometry. Statistical analysis included descriptive statistics, logistic regression, and Pearson correlation.ResultsMore than 80% of positive samples with aCL and aB2GP1 at high titers - but not low titers - were positive at a retest. Non-criteria aPL (aPS/PT) followed a similar trend. aCL and aB2GP1 measured with two different technologies were highly correlated. PC4d and IgG of the three aPL were at best moderately correlated even when only positive aPL samples were analyzed (coefficient: 0.1917 to 0.2649).ConclusionsHigh titers aPL are often persistently positive, allowing an earlier diagnosis and risk assessment at the time of the initial screening. Conversely, a retest may be necessary for low titers. The high correlation between two methodologies suggests that these findings are independent of assay platform. The low to moderate correlation between PC4d and aPL might suggest a possible additive value to evaluate association with thrombosis in autoimmune diseases.

Platelet bound complement split product (PC4d) is a marker of platelet activation and arterial vascular events in Systemic Lupus Erythematosus

Platelet-bound complement activation products (PC4d) are associated with thrombosis in Systemic Lupus Erythematosus (SLE). This study investigated the effect of PC4d on platelet function, as a mechanistic link to arterial thrombosis. In a cohort of 150 SLE patients, 13 events had occurred within five years of enrollment. Patients with arterial events had higher PC4d levels (13.6 [4.4–24.0] vs. 4.0 [2.5–8.3] net MFI), with PC4d 10 being the optimal cutoff for event detection. The association of arterial events with PC4d remained significant after adjusting for antiphospholipid status, smoking, and prednisone use (p = 0.045). PC4d levels correlated with lower platelet counts (r = −0.26, p = 0.002), larger platelet volumes (r = 0.22, p = 0.009) and increased platelet aggregation: the adenosine diphosphate (ADP) concentration to achieve 50% maximal aggregation (EC50) was lower in patients with PC4d 10 compared with PC4d < 10 (1.6 vs. 3.7, p = 0.038, respectively). These results suggest that PC4d may be a mechanistic marker for vascular disease in SLE.

Association of Higher Hydroxychloroquine Blood Levels With Reduced Thrombosis Risk in Systemic Lupus Erythematosus

Hydroxychloroquine (HCQ) has a primary role in the prophylaxis and treatment of systemic lupus erythematosus (SLE) and may be protective against thrombosis in SLE. Optimal weight-based dosing of HCQ is unknown. This study examined the usefulness of HCQ blood monitoring in predicting thrombosis risk in a longitudinal SLE cohort. HCQ levels were serially quantified from EDTA whole blood by liquid chromatography-tandem mass spectrometry. Mean HCQ blood levels calculated prior to thrombosis or until the last visit were compared between patients with and without thrombosis using t-test. Pooled logistic regression was used to analyze the association between rates of thrombosis and HCQ blood level. In 739 patients with SLE, thrombosis occurred in 38 patients (5.1%). Mean HCQ blood level was lower in patients who developed thrombosis vs without thrombosis (720±489 vs 935±580, p=0.025). Thrombosis rates were reduced by 12% for every 200 ng/mL increase in the most recent HCQ blood level (0.87 [0.78, 0.98], p=0.025) and by 13% for mean HCQ blood level (rate ratio 0.87 [0.76,1.00], p=0.056). Thrombotic events were reduced by 69% in patients with mean HCQ blood levels >1068 ng/mL vs <648 ng/mL (0.31 [0.11, 0.86], p=0.024). This remained significant after adjustment for confounders (0.34 [0.12, 0.94], p=0.037). Low HCQ blood levels are associated with thrombotic events in SLE. Longitudinal measurement of HCQ levels may allow for personalized HCQ dosing strategies. Recommendations for empirical dose reduction may reduce or eliminate the benefits of HCQ in this high-risk population.

Galectin-3-binding protein is a novel predictor of venous thromboembolism in systemic lupus erythematosus.

Venous (VTE) and arterial (AT) thrombosis in systemic lupus erythematosus (SLE) are poorly explained and difficult to predict. Leptin and tumour necrosis factor-like weak inducer of apoptosis (TWEAK) have been linked to subclinical atherosclerosis and galectin-3-binding protein (G3BP) to type I interferon activation and a pro-thrombotic environment. Thus, we explore serum G3BP, interferon gamma-induced protein 10 (IP-10), soluble CD163 (sCD163), TWEAK and leptin as predictors of VTE and AT, damage accrual, and all-cause mortality during follow-up in a Swedish SLE cohort. Baseline data were available from 162 SLE patients. VTE (deep vein thrombosis and/or pulmonary embolism), AT (myocardial infarction and/or stroke), damage accrual, and survival data were the main study outcomes and available at follow-up (median of five years). Baseline serum G3BP, IP-10, sCD163, TWEAK and leptin were measured and analysed by univariable and multivariable methods for association to the study outcomes. During the follow-up, 10 (6%) VTE and 13 (8%) AT events occurred. The SLICC/ACR Damage Index increased in 78 (48%) patients, and 19 (12%) patients died. In the univariable regression analysis G3BP levels were significantly associated with an increased risk of VTE (hazard ratio (HR) 1.11, 95% confidence interval (CI): 1.01-1.22, p=0.03). This persisted in the adjusted multivariable analyses (HR 1.18, 95% CI: 1.05-1.33, p=0.007). The other biomarkers were not associated with AT/VTE, damage accrual, or all-cause mortality. Our study identifies serum G3BP as a novel predictor of VTE in SLE. Further studies are needed to understand the role of G3BP in VTE and translate this into clinical practice.

Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus.

We evaluated which aPL combinations increase the risk of future thrombosis in patients with SLE. This prospective cohort study consisted of SLE patients who had been tested for all seven aPL (LA, aCL isotypes IgM, IgG and IgA, and anti-β2-glycoprotein I isotypes IgM, IgG and IgA). Pooled logistic regression was used to assess the relationship between aPL and thrombosis. There were 821 SLE patients with a total of 75048 person-months of follow-up. During the follow-up we observed 88 incident cases of thrombosis: 48 patients with arterial, 37 with venous and 3 with both arterial and venous thrombosis. In individual models, LA was the most predictive of any [age-adjusted rate ratio 3.56 (95% CI 2.01, 6.30), P < 0.0001], venous [4.89 (2.25, 10.64), P < 0.0001] and arterial [3.14 (1.41, 6.97), P = 0.005] thrombosis. Anti-β2-glycoprotein I IgA positivity was a significant risk factor for any [2.00 (1.22, 3.3), P = 0.0065] and venous [2.8 (1.42, 5.51), P = 0.0029] thrombosis. Only anti-β2-glycoprotein I IgA appeared to add significant risk to any [1.73 (1.04, 2.88), P = 0.0362] and venous [2.27 (1.13, 4.59), P = 0.0218] thrombosis among those with LA. We created an interaction model with four categories based on combinations of LA and other aPL to look at the relationships between combinations and the risk of thrombosis. In this model LA remained the best predictor of thrombosis. Our study demonstrated that in SLE, LA remained the best predictor of thrombosis and adding additional aPL did not add to the risk, with the exception of anti-β2-glycoprotein I IgA.

SAT0203 SINGLE LAC POSITIVITY VERSUS DOUBLE AND TRIPLE POSITIVITY FOR THROMBOSIS IN SLE

Background:The antiphospholipid syndrome (APS) is defined by the development of venous and/or arterial thromboses, and pregnancy morbidity, in the presence of antiphospholipid antibodies (aPL); lupus anticoagulant, moderate-to-high titer anticardiolipin (aCL) and anti-β2-glycoprotein (aB2GPI). It has been suggested that the incidence of thromboembolic events were significantly higher in the triple positive subjects, and the rate of pregnancy loss was also significantly much higher in double positive subjects (1). On the other hand several studies showed that LAC is more highly associated with thrombosis risk (2).Objectives:We aimed to investigate the risk of thrombosis in Systemic Lupus Erythematosus (SLE) patients with single LAC positivity versus double and triple positivity in Hopkins Lupus Cohort.Methods:The Hopkins Lupus Cohort is a prospective longitudinal cohort of SLE patients ongoing since 1987. This analysis was based on cohort experience from 2003 through October 2019. Anticardiolipin and anti-Beta2 glycoprotein were defined as positive when the antibody titer exceeded 20 units. The lupus anticoagulant was determined by dilute Russell’s viper venom time (dRVVT) and confirmatory mixing studies, if prolonged. It is defined as positive if a patient had a dRVVT of 45 or more second and a positive confirm ratio of more than 1.4. For each aPL, we defined the patient as positive at a given month of follow up if they ever had a positivity in previous measures. The relationships between thrombosis and aPL were adjusted for number of prior aPL assessment.Results:There were 805 patients with a complete profile of 7 antiphospholipid antibodies, with a total of 73417 person months (6118 person years) of follow up. For any thrombosis when compared to patients with LAC positivity only, double positivity with any isotypes [1.15(0.50, 2.66) p=0.7484] and triple positivity with any isotypes [1.68(0.74, 3.80), p=0.2145] showed a higher point estimates but statistically not significant (Table 1).Table 1.Single, double and triple positive patterns and the risk of any thrombosis.PatternNumber of eventsPerson-yearsRate per 1000 person-yearsadjusted RR (95% CI)p-valueLAC positivity only1063315.81.00 (Ref)Never any aPL33258112,80.73(0.36, 1.47)0.3819any aCL positivity only67937,60.43(0.16, 1.18)0.1028any aB2GPI positivity only751713,50.78(0.30,2.05)0.6195any aCL and aB2GPI positivity only540412,40.71(0.24,2.04)0.5211LAC and ACL positivity740617,31.15(0.50,2.66)0.7484LAC and aB2GPI positivity1249024,5Triple positivity01470,01.68(0.74,3.80)0.2145Conclusion:We found that triple or double positive aPL profiles are not superior to single LAC positivity in their association with any thrombosis in SLE patients.

Profiling of non-criteria antiphospholipid antibodies in patients with SLE: differentiation of thrombotic SLE patients and risk of recurrence of thrombosis.

To reveal the clinical significance of criteria and non-criteria antiphospholipid antibodies detected by line immunoassay in comparison with ELISA, systemic lupus erythematosus patients with and without thrombotic events were investigated. Thus, 107 systemic lupus erythematosus patients (48% with deep vein thrombosis or/and arterial thrombosis) and 120 healthy donors were enrolled. Serum antiphospholipid antibodies were detected by ELISA (Orgentec Diagnostika, Germany) and line immunoassay (GA Generic Assays, Germany). Lupus anticoagulant and IgG to cardiolipin and β2GPI but not IgM as well as triple positivity by ELISA and line immunoassay were linked with thrombosis in systemic lupus erythematosus. IgG to phosphatidylinositol and phosphatidylserine by line immunoassay showed significantly higher levels in systemic lupus erythematosus with deep vein thrombosis/arterial thrombosis than without and were independent risk factors for deep vein thrombosis (odds ratio 3.9, 95% confidence interval 1.1, 13.2) and arterial thrombosis (odds ratio 5.1, 95% confidence interval 1.3, 19.8) as well as thrombosis (odds ratio 3.6, 95% confidence interval 1.1, 11.3) and recurrence thereof (odds ratio 6.9, 95% confidence interval 2.1, 22.6), respectively. The occurrence of >4 IgG antiphospholipid antibodies by line immunoassay was an independent risk factor for thrombosis (odds ratio 10.9, 95% confidence interval 1.2, 101.5), arterial thrombosis (odds ratio 14.6, 95% confidence interval 2.5, 86.3), deep vein thrombosis (odds ratio 5.8, 95% confidence interval 1.0, 32.4) and recurrence of thrombosis (odds ratio 35.9, 95% confidence interval 3.8, 342.8). Line immunoassay is a promising multiplex test for the simultaneous detection of criteria and non-criteria antiphospholipid antibodies. Profiling of antiphospholipid antibodies by line immunoassay can differentiate systemic lupus erythematosus patients with thrombosis from systemic lupus erythematosus patients without and assess the risk for thrombosis and recurrence thereof.

Cerebral venous thrombosis in systemic lupus erythematosus

Cerebral venous thrombosis in systemic lupus erythematosus

Efficacy and tolerance of selective and non-selective factor Xa inhibitors in the prevention of thrombosis in kidney disease in patients with systemic lupus erythematosus and antiphospholipid syndrome

The use of factor Xa inhibitors is justified in the therapy of thrombosis in antiphospholipid syndrome (APS) and active lupus nephritis (LN). To monitor the efficacy and safety of these drugs, plasma anti-Xa (aXa) activity is determined. Objective : to assess the aXa activity of selective and non-selective factor Xa inhibitors in patients with systemic lupus erythematosus (SLE) and APS depending on how they affect the kidneys. Patients and methods. Clinical and laboratory findings were prospectively analyzed in SLE and APS patients who long received low molecular weight heparins (LMWHs) and selective Xa inhibitors, such as fondaparinux and rivaroxaban. The investigation enrolled 70 patients (54 females and 16 males) aged 39 years (range, 31 to 43 years) with SLE (n=15 (21%)), primary APS (PAPS) (n=10 (14%)), and SLE + APS (n=45 (65%)). Results . Kidney disease was diagnosed in 33 (47%) of the 70 patients. LN was detected in 15 (25%) of the 60 patients: 10 and 5 patients with SLE and SLE + APS, respectively. APS nephropathy (APSN) was manifested by elevated creatinine and urea levels with normal urine sediment and no history of glomerulonephritis and was observed in 18 (33%) of the 55 patients: in 16 with SLE + APS and 2 with PAPS. The therapeutic aXa range of 0.1—1.5 IU/ml was found in 43 (61%) of the 70 patients, low and high aXa activities were seen in 14 (20%) and 13 (19%) patients, respectively. In patients with APSN, the creatinine clearance (CC) depended on aXa levels: the highest CC was noted in patients with aXa >1.5 IU/mL, the lowest CC was in those with aXa <0.9 IU/ mL (p=0.046). The levels of aXa above the therapeutic range were more common in patients taking fondaparinux (9 (31%) out of the 29 patients) than in those using nadroparin (2 (7%) out of the 29 patients) (odds ratio (OR) 1.92; 95% confidence interval (CI), 1.25—2.97; p=0.04). In the fondaparinux group, high aXa was more frequently observed in patients with high SLE activity (7 (47%) out of the 15 patients) than in those with moderate or mild SLE activity (none out of the 7 patients) (OR 1.88; 95% CI, 1.17—3.01; p=0.037) and was unassociated with LN. The highest aXa level with no signs of hemorrhage was 2.08 IU/mL. Conclusion. The level of aXa is a qualitative laboratory marker for the efficacy and safety of LMWHs and fondaparinux. In patients with APS, the enhanced aXa activity of LMWHs and fondaparinux was associated with elevated CC and was not accompanied by hemorrhage. Fondaparinux is an effective and safe anticoagulant for the treatment and prevention of thrombosis in SLE and APS. The therapeutic window for aXa should be extended in these patients.

Clinical significance of fibromyalgia syndrome in different rheumatic diseases: Relation to disease activity and quality of life

ObjectiveTo describe the frequencies of fibromyalgia syndrome (FMS) in various rheumatic diseases; rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Behçets disease (BD) patients and to study the relation to clinical manifestations and quality of life (QoL). Patients and methods160 patients (50 RA, 50 SLE, 30 SSc and 30 BD) and matched corresponding healthy controls were included. Disease activity was assessed using disease activity score in 28 joints (DAS28) for RA, SLE Disease Activity index (SLEDAI), modified Rodnan skin score for SSc and BD Current Activity Form (BDCAF). The QoL was also recorded. Severity in FMS cases was estimated using the revised Fibromyalgia Impact Questionnaire score. ResultsIn the RA, SLE, SSc and BD patients, FMS was found in 14%, 18%, 6.67% and 3.33% respectively compared to 2.1%, 3%, 3.3% and 0% in their corresponding controls. In RA patients, DAS28 was significantly higher in those with FMS (p=0.009) and significantly correlated with both Widespread Pain Index (WPI) (p=0.011) and Symptom Severity (SS) scale (p=0.012). The QoL scale in those with FMS was significantly worse (62.3±7.9) compared to those without (71.7±14.4) (p=0.023). In SLE patients, The WPI and SS both significantly correlated with the presence of thrombosis (r=0.28, p=0.049 and r=0.43, p=0.002 respectively). The SS scale tended to correlate with the SLEDAI (r=0.28, p=0.05). In BD patients, BDCAF and WPI significantly correlated (p=0.03). ConclusionFibromyalgia syndrome is more frequent in rheumatic diseases, could be related to the disease activity in RA and BD patients and to thrombosis in SLE and affected the QoL in RA.

тромбозы при болезни Бехчета: от патогенеза к лечению

Введение. Болезнь Бехчета (ББ) – системный васкулит неизвестной этиологии, характеризующийся рецидивами язвенного процесса в ротовой полости и на гениталиях, частым поражением глаз и рядом проявлений, включающих патологию суставов, желудочно-кишечного тракта, нервной системы и сосудов. Цель исследования: определить частоту и локализацию сосудистых проявлений у больных с ББ, уточнить связь последних с полом, возрастом и другой клинической симптоматикой ББ. Материалы и методы. Обследовано 250 больных ББ, сосудистая патология выявлена у 63 (25,2%) пациентов. Возраст больных с сосудистыми проявлениями составил 34,8 ± 10,4 лет, соотношение мужчины:женщины – 3,5:1. Сосуды вовлекались в процесс чаще в течение первых трех лет болезни. Поражалось в основном венозное русло, доля больных с артериальной патологией составила 9,5%. Результаты. У пациентов с сосудистой патологией по сравнению с больными без тромбозов достоверно чаще выявлялись узловатая эритема (71% против 44%; р = 0,002) и эпидидимит (22,4 % против 10,9%; р = 0,04), а генерализованный увеит (17,4% против 32%; р = 0,002) и ангиит сетчатки (22% против 40,6%; р = 0,008) встречались достоверно реже. В системе коагуляции у больных ББ с и без сосудистой патологии достоверных различий не выявлено. Заключение. Сосудистые нарушения выявлены у ¼ больных (преимущественно мужчин молодого возраста), развивались чаще в первые три года болезни и ассоциировались с узловатой эритемой, эпидидимитом и положительным тестом патергии. Introduction. Behcet's disease (BB) is a systemic vasculitis of unknown etiology; it is characterized by recurrent aphthous stomatitis, genital ulcers, uveitis and other manifestations including arthritis, pathology of gastrointestinal tract, nervous system and blood vessels. The aim of study: to determine frequency and localization of vascular manifestations in patients with BB, to clarify the relationship of manifestations with sex, age and other clinical symptoms of BB. Materials and methods. We examined 250 patients with BB, vascular pathology was revealed in 63 (25,2%) patients. The age of patients with vascular manifestations was 34,8 ± 10,4 years, the ratio of men:women was 3,5:1. Vessels were involved in the process more often during the first three years of the disease. Mainly veins were affected, arterial pathology had 9,5% of patients. Results. In patients with vascular pathology erythema nodosum (71% vs. 44%, p = 0,002) and epididymitis (22,4% vs. 10.9%; p = 0,04) were significantly more frequent than in patients without thromboses, and panuveitis (17,4% vs. 32%; p = 0,002) and retinal vasculitis (22% vs. 40,6%; p = 0,008) were found significantly more rarely. There were no significant differences in coagulation system between patients with and without vascular pathology. Conclusion. Vascular disorders were detected in ¼ of patients (predominantly in men of young age), developed more often in the first three years of the disease and associated with erythema nodosum, epididymitis and a positive pathergy test.

Mechanisms of thrombosis in systemic lupus erythematosus and antiphospholipid syndrome.

The presence of antiphospholipid antibodies is one of the most common acquired risk factors for thrombosis. Antiphospholipid antibodies is a collective term for a set of autoantibodies with closely related but different specificity. Experiments in which isolated patient antibodies were injected into mice have shown that a specific subset of autoantibodies, those directed against the first domain of plasma protein β2-glycoprotein I, can explain the increased risk of thrombosis. Experiments performed with these mice have shown that autoantibodies against β2-glycoprotein I bind to and activate cells such as endothelial cells, monocytes, and platelets. Activation of these cells, all involved in the regulation of hemostasis, results in a shift towards a prothrombotic state. How this process is regulated, whether this is the only mechanism involved, and whether this is the only subpopulation responsible for the increased thrombotic risk is unknown. In this review, we will critically discuss what is known and what is debatable on the pathophysiology of antiphospholipid syndrome.

Clinical significance of fibromyalgia syndrome in different rheumatic diseases: Relation to disease activity and quality of life.

To describe the frequencies of fibromyalgia syndrome (FMS) in various rheumatic diseases; rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Behçets disease (BD) patients and to study the relation to clinical manifestations and quality of life (QoL). 160 patients (50 RA, 50 SLE, 30 SSc and 30 BD) and matched corresponding healthy controls were included. Disease activity was assessed using disease activity score in 28 joints (DAS28) for RA, SLE Disease Activity index (SLEDAI), modified Rodnan skin score for SSc and BD Current Activity Form (BDCAF). The QoL was also recorded. Severity in FMS cases was estimated using the revised Fibromyalgia Impact Questionnaire score. In the RA, SLE, SSc and BD patients, FMS was found in 14%, 18%, 6.67% and 3.33% respectively compared to 2.1%, 3%, 3.3% and 0% in their corresponding controls. In RA patients, DAS28 was significantly higher in those with FMS (p=0.009) and significantly correlated with both Widespread Pain Index (WPI) (p=0.011) and Symptom Severity (SS) scale (p=0.012). The QoL scale in those with FMS was significantly worse (62.3±7.9) compared to those without (71.7±14.4) (p=0.023). In SLE patients, The WPI and SS both significantly correlated with the presence of thrombosis (r=0.28, p=0.049 and r=0.43, p=0.002 respectively). The SS scale tended to correlate with the SLEDAI (r=0.28, p=0.05). In BD patients, BDCAF and WPI significantly correlated (p=0.03). Fibromyalgia syndrome is more frequent in rheumatic diseases, could be related to the disease activity in RA and BD patients and to thrombosis in SLE and affected the QoL in RA.

Assessment of the independent associations of IgG, IgM and IgA isotypes of anticardiolipin with thrombosis in SLE

ObjectiveThe Sydney classification criteria for antiphospholipid syndrome include lupus anticoagulant or moderate-to-high titre anticardiolipin IgG or IgM. We explored the association of all anticardiolipin isotypes, lupus anticoagulant and the combination...

Catheter‐directed therapy for acute renal vein thrombosis in systemic lupus erythematosus: A case report

We report our experience using catheter-directed thrombectomy/thrombolysis (CDT) to treat a patient with acute renal vein thrombosis (RVT) associated with systemic lupus erythematosus (SLE). A 34-year-old woman presented with persistent left flank pain, and a renal ultrasonography examination revealed an enlarged left kidney. Contrast-enhanced computed tomography confirmed the presence of acute left RVT. Because medical treatment failed to relieve her pain and the renal function was deteriorating, we attempted to salvage the occluded left renal vein using an endovascular approach. The pain was completely relieved after a CDT and an overnight urokinase infusion. A follow-up computed tomography examination revealed the complete resolution of the thrombus. The creatinine level returned to normal (1.7-0.4 mg/dL), along with contrast enhancement in the left kidney, and this suggested the preservation of renal function. To our knowledge, this is the first report utilizing CDT to treat SLE-associated RVT. When the renal function is deteriorating, CDT is worth considering for RVT if conventional medical treatment has failed. © 2016 Wiley Periodicals, Inc.

The risk of pulmonary embolism and deep venous thrombosis in systemic lupus erythematosus: A general population-based study

ObjectiveTo estimate the future risk and time trends of newly diagnosed venous thromboembolism (VTE) in individuals with incident systemic lupus erythematosus (SLE) in the general population. MethodsUsing a population-based database that includes all residents of British Columbia, Canada we conducted a study cohort of all patients with incident SLE and up to 10 age-, sex-, and entry-time-matched individuals from the general population. We compared incidence rates of pulmonary embolism (PE), deep venous thrombosis (DVT), and VTE between the two groups according to SLE disease duration. We calculated hazards ratios (HR), adjusting for confounders. ResultsAmong 4863 individuals with SLE (86% female; mean age, 48.9 years), the incidence rates (IRs) of PE, DVT, and VTE were 2.58, 3.33, and 5.32 per 1000 person-years, respectively, whereas the corresponding rates in the comparison cohort were 0.67, 0.57, and 1.11 per 1000 person-years. Compared with non-SLE individuals, the multivariable HRs among SLE patients were 3.04 (95% CI: 2.08–4.45), 4.46 (95% CI: 3.11–6.41), and 3.55 (95% CI: 2.69–4.69), respectively. The age-, sex-, and entry-time-matched HRs for PE, DVT, and VTE were highest during the first year after SLE diagnosis [13.57 (95% CI: 7.66–24.02), 11.13 (95% CI: 6.55–18.90), and 12.89 (95% CI: 8.56–19.41), respectively]. ConclusionThese findings provide population-based evidence that patients with SLE have a substantially increased risk of VTE, especially in the first year after SLE diagnosis. Awareness and increased vigilance of this potentially fatal, but preventable, complication is recommended.

Thrombopoietin levels in systemic lupus erythematosus are linked to inflammatory cytokines, but unrelated to thrombocytopenia or thrombosis

Thrombopoietin (TPO) is a liver-produced protein that drives megakaryocyte maturation. TPO regulates platelet production and can increase platelet and endothelial reactivity. We investigated the relationship between TPO and the occurrence of thrombocytopenia and thrombosis in patients with systemic lupus erythematosus (SLE). We undertook a cohort study of SLE patients (n = 98) with clinical data collected simultaneously with sampling for TPO, inflammatory cytokines and autoantibody detection. TPO levels were measured by sandwich ELISA with patients with rheumatoid arthritis (RA) (n = 100) and controls (n = 79) as comparators. Disease associations were evaluated using non-parametric methods. TPO levels in SLE (median 8 pg/ml, mean 326, range 8992) were moderately increased compared with RA (median 8 pg/ml, mean 100, range 1659, p = 0.07) and controls (median 8, mean 94, range 2088, p = 0.1). Among SLE patients, TPO levels did not correlate with platelet count or levels of antiphospholipid antibodies. The prevalence of thrombocytopenic episodes, thrombotic events or active disease was not increased in patients with high TPO levels. TPO levels correlated with MIP-1α (Rs 0.56, p < 0.001), IL6 (Rs 0.26, p = 0.02) and IL4 (Rs 0.29, p = 0.01), and inversely correlated to C4 (Rs -0.23, p = 0.04). MIP-1α was the strongest independent predictor of increased TPO levels. TPO levels are elevated in 20% of patients, but are not closely related to the occurrence of thrombocytopenia or thrombosis in SLE. MIP1-alpha is the main factor driving higher TPO levels among patients with SLE, likely through its inhibitory effect on megakaryocyte function.

Brief Report: A Polymorphism in TLR2 Is Associated With Arterial Thrombosis in a Multiethnic Population of Patients With Systemic Lupus Erythematosus

ObjectiveThrombosis is a serious complication of systemic lupus erythematosus (SLE). Studies that have investigated the genetics of thrombosis in SLE are limited. We undertook this study to assess the association of previously implicated candidate genes, particularly Toll-like receptor (TLR) genes, with pathogenesis of thrombosis.MethodsWe genotyped 3,587 SLE patients from 3 multiethnic populations for 77 single-nucleotide polymorphisms (SNPs) in 10 genes, primarily in TLRs 2, 4, 7, and 9, and we also genotyped 64 ancestry-informative markers (AIMs). We first analyzed association with arterial and venous thrombosis in the combined population via logistic regression, adjusting for top principal components of the AIMs and other covariates. We also subjected an associated SNP, rs893629, to meta-analysis (after stratification by ethnicity and study population) to confirm the association and to test for study population or ethnicity effects.ResultsIn the combined analysis, the SNP rs893629 in the KIAA0922/TLR2 region was significantly associated with arterial thrombosis (logistic P = 6.4 × 10−5, false discovery rate P = 0.0044). Two additional SNPs in TLR2 were also suggestive: rs1816702 (logistic P = 0.002) and rs4235232 (logistic P = 0.009). In the meta-analysis by study population, the odds ratio (OR) for arterial thrombosis with rs893629 was 2.44 (95% confidence interval 1.58–3.76), without evidence for heterogeneity (P = 0.78). By ethnicity, the effect was most significant among African Americans (OR 2.42, P = 3.5 × 10−4) and European Americans (OR 3.47, P = 0.024).ConclusionTLR2 gene variation is associated with thrombosis in SLE, particularly among African Americans and European Americans. There was no evidence of association among Hispanics, and results in Asian Americans were limited due to insufficient sample size. These results may help elucidate the pathogenesis of this important clinical manifestation.