Search

Aim. To study the indices of standard coagulogram and thrombodynamics test in native plasma and in the test with phospholipids in relation to the activity of rheumatoid arthritis (RA) and the ongoing therapy.Material and methods. We examined 28 patients with rheumatoid arthritis and eight age- and sex-matched healthy controls: 11 patients with high rheumatoid arthritis activity (DAS28>5.2) (Group 1), nine patients with low and moderate rheumatoid arthritis activity (DAS28˂ 5.2) (Group 2) and eight rheumatoid arthritis patients receiving anticoagulants (Group 3).Results. Elevated fibrinogen was more common in the RA patient groups: 5/11(45%) in group 1, 3/9(33%) in group 2 and 3/8(38%) in group 3. In the control group, fibrinogen was normal, p˂ 0.05. Increased SFMC was found in all patients in all three groups (100%) and only in 2 of the controls (25%), with p˂ 0.05. Mean clot density was significantly higher in RA groups than in controls: 26811, 25437 and 24740 versus 20631 c.u. in groups 1, 2, 3 and control, respectively, p˂ 0,01. In patients with anticoagulants, lag time (1.4 minutes) was longer than without anticoagulants (1.1-1.2 minutes), with p˂ 0.05 in all cases. Spontaneous clots were detected only in patients: 3 in groups 1 and 1 each in groups 2 and 3. Hypocoagulation was detected only in group 3 in 1/8(12%) patients, and thrombotic readiness status was detected in groups 1 and 2: in 2/11(18%) and 1/9(11%) patients, respectively. The frequency of normal- and hypercoagulation did not differ between the patient and control groups.Conclusion. According to the thrombodynamics test, hypercoagulability is present in RA patients. Thrombodynamics test can be used to identify the risk of thrombosis and to individualize therapy in RA patients.

The paper presents information on the 27th Congress of the International Society on Thrombosis and Hemostasis, which was held in Melbourne (Australia) in July 2019. This congress is the world’s leading forum on thrombosis and hemostasis, as well as on the causes of bleeding and their clinical manifestations. It unites all specialists who are relevant to this problem.

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

Objective: to determine risk factors (RFs) for venous thromboembolic events (VTE) in patients with rheumatoid arthritis (RA).Subjects and methods: The investigation enrolled 374 patients (311 women and 63 men) with a reliable diagnosis of RA who met the 2010 ACR/EULAR classification criteria. The patients' mean age was 53.7±13.6 years; the disease duration was 12.1±10.7 years. All the patients were treated at the V.A. Nasonova Research Institute of Rheumatology Clinic during the period from 2014 to 2017. A standard clinical examination of the peripheral joints was performed. RA activity was measured using DAS28. A survey was made using a questionnaire including questions on traditional RFs for VTE and RFs that might be caused by RA and its therapy. Results and discussion. VTE were recorded in 45 (12%) out of the 374 patients. Group 1 included 45 patients with VTE; Group 2 consisted of 329 patients without VTE. Multidimensional analysis showed an increased risk of developing VTE in RA under the influence of the following factors: high inflammatory activity; lower extremity varicose veins; hypercholesterolemia; and hypertension. Their weighted coefficients were 1.1, 2.5, 1.0, and 0.9, respectively. According to the obtained model (pConclusion: The increased risk for VTE in RA patients determines the need for its timely assessment, by taking into account the known risk factors as both standard ones and those caused by the disease itself and its therapy. This risk assessment is necessary for the timely adequate treatment and prevention of thrombotic events in RA.

The aim of the study was to evaluate the anti - Xa - activity (aXa) of selective and non - selective factor Xa inhibitors in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) patients according to clinical implications and laboratory parameters.Clinical and laboratory data were analyzed retrospectively in SLE and APS patients who protractedly received low weight molecular heparins (LWMH) and selective factor Xa inhibitors fondaparinux and rivaroxaban. The study included 70 patients in the middle age 39 [31; 43] years: 15/70 (21%) - with SLE, 10/70 (14%) - with APS and 45/70 (65%) - with SLE and APS (SLE+APS). All the patients received anticoagulants: 29 patients - nadroparin (98.3 [67.8; 129.5] IU/kg/day), 29 patients - fondaparinux (5 [5; 7.5] mg/day), 3 patients - enoxaparin (1.2 [0.8; 1.5] mg/day) and 9 patients - rivaroxaban (20 mg/day). All the patients signed informed consents.aXa therapeutic range of 0.1-1.5 IU/ml was found in 43/70 (61%) patients, low aXa - in 14/70 (20%) and high aXa - in 13/70 (19%) patients. Patients with low aXa underwent anticoagulant dose correction. There were not any major bleedings and thrombosis relapses in the study. Increased aXa was more common in patients, who took fondaparinux (31%), than in those, who took nadroparin (7%) and rivaroxaban (23%), p=0.02. Patients with enoxaparin had normal aXa range. In the absence of bleeding in SLE and APS patients, received anticoagulants in standardized therapeutic dose, the next factors influenced the aXa range excess: valvular heart disease (VHD) with the 3rd stage of mitral valve insufficiency as a result of aseptic Libman-Sacks endocarditis (odds ratio - OR 9.02, 95% confidential interval - CI [1.53; 53.12], p=0.015), peripheral artery disease in analogy with arteritis obliterans (AO) (OR 6.86, 95% CI [1.25; 37.71], p=0.027), and also triple - positivity of all types of antiphospholipid antibodies (OR 4.93, 95% CI [1.11; 21.99], p=0.036). According to found logistic regression model, aXa range excess risk can be prognosticated by the next formula: Z = -3.98 + 2.2 × VHD (yes-1/no-0) + 1.9 × AO (yes-1/no-0) + 1.6 × Triple - positivity (yes-1/no-0). Classified function value Z=0.39 defines the patients group with aXa range excess. Thus the value Z0.39 indicates aXa range excess in the absence of bleeding, herewith sensibility is of 77% and specificity is 86%, positive prognostic value is 84.3%.In SLE and APS patients the next clinical and immunologic manifestations influenced the aXa therapeutic range excess: peripheral artery disease in analogy with AO, earlier aseptic Libman-Sacks endocarditis with the 3rd stage of mitral valve insufficiency and triple - positivity of all types of antiphospholipid antibodies, that does not need LWMH and fondaparinux dose correction. In contrast, anticoagulant dose reduction can cause clinical symptoms progression. Therapeutic aXa range in such patients should be extended.Цель исследования - оценить анти - Ха - активность (аХа) селективных и неселективных ингибиторов Ха - фактора у больных системной красной волчанкой (СКВ) и антифосфолипидным синдромом (АФС) в зависимости от клинических проявлений и лабораторных показателей. Материалы и методы. У больных СКВ и АФС, длительно получавших низкомолекулярные гепарины (НМГ) и селективные ингибиторы Ха фондапаринукс и ривароксабан, ретроспективно проанализированы данные клинических и лабораторных исследований. В исследование включено 70 пациентов в возрасте 39 [31; 43] лет, из них 15/70 (21%) пациентов с СКВ, 10/70 (14%) - с АФС и 45/70 (65%) - с СКВ+АФС. Больные получали антикоагулянты: 29 пациентов - надропарин (98,3 [67,8; 129,5] МЕ/кг/сут), 29 пациентов - фондапаринукс (5 [5; 7,5] мг/сут), 3 больных - эноксапарин (1,2 [0,8; 1,5] мг/сут) и 9 пациентов - ривароксабан (20 мг/сут). Все пациенты подписали информированное согласие. Результаты. Терапевтический интервал аХа 0,1-1,5 МЕ/мл зарегистрирован у 43/70 (61%) больных. Низкая аХа выявлена у 14/70 (20%) больных, высокая аХа - у 13/70 (19%). Пациентам с низкой аХа проводилась коррекция дозы антикоагулянта. Массивных кровотечений и рецидивов тромбозов в исследовании не зарегистрировано. Превышение терапевтического интервала аХа более часто встречалось на фоне фондапаринукса (31%), чем на фоне надропарина (7%) и ривароксабана (23%), р=0,02. На фоне эноксапарина аХа была в пределах нормы. В отсутствие кровотечения у больных СКВ и АФС, получавших антикоагулянты в стандартной терапевтической дозе, на повышение аХа оказывали влияние следующие факторы: порок сердца с формированием митральной недостаточности Ⅲ степени в исходе асептического эндокардита Либмана-Сакса (отношение шансов - ОШ 9,02, 95% доверительный интервал - ДИ [1,53; 53,12], p=0,015), поражение артерий по типу облитерирующего эндартериита (ОЭ) с артериальной недостаточностью (ОШ 6,86, 95% ДИ [1,25; 37,71], p=0,027), а также позитивность по всем трем серологическим маркерам АФС (ОШ 4,93, 95% ДИ [1,11; 21,99], p=0,036). Согласно полученной логистической регрессионной модели риск повышения аХа можно спрогнозировать по следующей формуле: Z = -3,98 + 2,2 × Порок (да-1/нет-0) + 1,9 × ОЭ (да-1/нет-0) + 1,6 × Triple-позитивность (да-1/нет-0). Значение классификационной функции Z=0,39 определяет группу пациентов с повышенным аХа. Соответственно значение Z0,39 указывает на повышение аХа в отсутствие кровотечения, при этом чувствительность составляет 77%, специфичность - 86%, положительная прогностическая точность - 84,3%. Заключение. На повышение аХа у больных АФС и СКВ влияли следующие клинические и иммунологические проявления: поражение сосудов по типу ОЭ, перенесенный асептический эндокардит Либмана-Сакса с формированием высокой степени митральной недостаточности, наличие всех трех маркеров АФС, что не требует коррекции дозы НМГ и фондапаринукса. Напротив, уменьшение дозы антикоагулянта может вызвать ухудшение клинической симптоматики. Терапевтическое окно аХа у таких пациентов должно быть расширено.

Systemic lupus erythematosus (SLE) - chronic systemic disease, which associates with genetic defects of immunoregulatory processes and leads to uncontrolled production of antibodies to native cells and its elements with autoimmune inflammation development. There is a case report of human intravenous immunoglobulin use in lupus patient with the multiple resistances to antirheumatic drugs and many adverse reactions of the therapy.

Objective: to assess the psychometric properties (reliability, sensitivity, and validity) of a Russian-language version of the VEINES-QOL/Sym questionnaire in patients with rheumatic diseases and lower extremity chronic venous diseases. Subjects and methods. The investigation enrolled 89 patients (66 (74%) women and 23 (26%) men) (their mean age was 46.3±13.4 years) with rheumatic diseases. The majority (n=62 (70%)) of patients were recorded to have a history of one case of venous thrombosis of the lower extremity; the others (n=27 (30%)) had more than one case of thrombosis. To calculate the scores the VEINES-QOL/Sym questionnaire, a standard method proposed by its authors was used. The patients filled out the VEINES-QOL/Sym questionnaire thrice: on inclusion, at 2 weeks, and at 6 months. Results and discussion. The internal consistency (Cronbach’s α coefficient) of VEINES-QOL and VEINES-Sym was equal to 0.973 and 0.975, respectively, which reflects the high level of reliability. The coefficient κ varied from 0.825 to 1, which indicates good reproducibility (p < 0.001). The correlation coefficients of VEINES-QOL and VEINES-Sym with the physical component of SF36 were 0.59 and 0.42, and those with its psychological component were 0.42 and 0.35, respectively (p

Thew antinuclear antibodies (ANA) consist heterogeneous group of auto antibodies reacting with various components of nucleus and cytoplasm. The ANA is a main serological marker of systemic lupus erythematosus (SLE). The implementation in clinical practice of new highly productive techniques of immune analysis using automated systems sets up prerequisites for standardization and amelioration of reproducibility of detection of ANA. The study was carried out to compare diagnostic significance of automated techniques of screening detection of ANA (indirect immunofluorescence test on cells HEp-2 (IIFT-HEp-2)), enzyme-linked immunosorbent assay (ELISA) and multi-complex immune analysis (MIA, using suspension technology xMAP) in serum of patients with SLE. The serums from 94 patients with SLE were analyzed. The comparison group included 70 patients with other rheumatic diseases. The control group consisted of 30 healthy donors. The screening detection of ANA using technique IIFT-HEp-2 was implemented on automated platform AKLIDES, ELISA - on automated analyzer ALEGRIA and MIA on automated analyzer BioPlex 2200. The technique IIFT-HEp-2 demonstrated the most high diagnostic sensitivity as compared with ELISA and MIA- BioPlex 2200 (96.8%; 79.8% and 82.9% correspondingly). The general diagnostic specificity of detection of ANA using technique IIFT-HEp-2 was lower than in case of ELISA and MIO-BioPlex 2200 (40%, 70% and 57% correspondingly). In the group of healthy donors the lowest diagnostic specificity was observed in ANA screening analysis using MIA-BioPlex 2200 (80%) while in case of applying IIFT-HEp-2 and ELISA indices of diagnostic specificity made up 93.3% and 96.7% correspondingly. The ANA analysis of mix of 26 nuclear antigens using ELISA technique was a reliable laboratory test for diagnostic of SLE (likelihood ratio of positive result - 2.66). By the level of likelihood ratio of negative result of the IIFT-HEp-2 technique was more informative test for exclusion of diagnosis of SLE than techniques of ELISA and MIA-BioPlex 2200 (0.08; 0.29 and 0.3 correspondingly). The detection of ANA using technique of is the most preferable primary screening test for diagnostic of SLE. The ELISA of antibodies to mix of nuclear antigens and MIA on the basis of xMAP technology are less preferable screening tests for diagnostic of SLE as compared with IIFT-HEp-2 because of false-negative results in 20% and 17% of cases correspondingly. ELISA and MIA are to applied as confirmatory screening tests permitting to detect antigen-specific ANA in patients with SLE with positive results of IIFT-HEp-2.

The article presents the data of international registries and cohort studies of systemic lupus erythematosus (SLE). It justifies the purpose and objectives of the international registry of SLE patients, a Eurasian cohort (RENAISSANCE), which was launched in 2012 and amalgamated the leading rheumatology centers of the Russian Federation (V.A. Nasonova Research Institute of Rheumatology; Department of Rheumatology, Pacific State Medical University), Kazakhstan (Department of Rheumatology, S.D. Asfendiyarov Kazakh National Medical University), and Kyrgyzstan (Academician M. Mirrakhimov National Center for Cardiology and Therapy), which mainly concentrate patients with the acute course of this disease. The first data of the registry are given.

Objective: to determine the incidence and risk factors of venous thromboembolic events (VTEE) in patients with rheumatoid arthritis (RA).Subjects and methods. The investigation enrolled 362 patients (302 women and 60 men) with RA fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism criteria. The patients' mean age was 53.7±13.3 years; the disease duration was 12.4±10.9 years. All the patients were treated at the V.A. Nasonova Research Institute of Rheumatology in the period 2014 to 2015. Each patient underwent standard clinical examination of peripheral joints. RA activity was assessed with DAS28. There was a questionnaire survey that included traditional risk factors for VTEE and risk factors that might be due to RA and its therapy.Results and discussion. 34 (9.9%) patients were found to have VTEE during their hospitalization or in their history. In 32 of them thromboses were located in the veins of the lower extremities, namely 18 and 14 patients had thromboses in the distal and proximal segments, respectively. One patient was recorded to have upper extremity vein thrombosis and another had central retinal vein thrombosis. Lower extremity deep vein thrombosis was complicated by pulmonary thromboembolism in one case. Multivariate analysis has shown that the risk factors of VTEE in RA patients are bed care, heart failure, varicose vein disease, and oral administration of glucocorticoids (GC) and intraarticular GC administration (>5 injections); the weighted coefficients of the risk factors are 1.0, 0.92, 3.13, 0.02, and 0.52, respectively. According to the model obtained (p < 0.0001), the risk of VTEE can be predicted using the following formula: Z = 1.0 × bed care (yes, 1 / no, 0) + 0.92 × heart failure (yes, 1 / no, 0) + 3.13 × varicose vein disease (yes, 1 / no, 0) + 0.02 × oral GC use (yes, 1 / no, 0) + 0.52 × intraarticular GC administration (>5 injections; yes, 1 / none, 0).Conclusion. The risk of VTEE should be assessed to timely prescribe adequate prophylactic treatment and to prevent thrombotic events in RA. The classification function value Z = 1.65 identifies groups of patients at high and low risk for VTEE. Accordingly, the value Z >1.65 determines the high risk of thrombosis; in this case it has a sensitivity of 64%, a specificity of 82%, and a positive prognostic accuracy of 80%.

Therapy with intravenous human immunoglobulin (IVIG) was and continues to remain essential for a number of diseases. At the same time the evidence base for IVIG use is extremely small in rheumatology. Clinical experience shows that IVIG is effective in treating thrombocytopenic purpura, Guillain–Barre syndrome, and chronic inflammatory demyelinating polyneuropathy, which develop in the presence of rheumatic diseases, such as systemic lupus erythematosus, inflammatory myopathies, and antineutrophil cytoplasmic antibody-associated vasculitides. The review considers indications for the use of IVIG, its dosage regimen, benefits, and adverse reactions and analyzes the Russian and foreign literature on this issue.

The paper presents a brief review of the proceedings of the 15th Mediterranean Rheumatology Congress that was held in Istanbul, Turkey, in August 2014. This congress unites the scientists and physicians of Mediterranean countries and focuses the attention of rheumatologists and allied health professionals on the geographical and ethnical features of the pattern of human diseases caused by the inflammatory and metabolic involvement of the locomotor apparatus, as well as the peculiarity of the course of rheumatic diseases and treatment response. The goal of the congress is not only to present information on the latest advances in rheumatology, but also to create conditions for the academic exchange of knowledge at an international level and for the promotion of new investigations.

Glucocorticoids (GCs) are first-line drugs to treat systemic lupus erythematosus (SLE) of both high and moderate activities. These are the only agents that are able to provide so prompt anti-inflammatory and immunosuppressant effects in rheumatic diseases. Along with antimalarials and immunosuppressants, GCs are used in the standard classical treatment regimen for SLE; however, despite the high efficacy of these drugs, their related immediate or delayed adverse reactions are one of the major problems in the management of a patient with SLE. Occasionally, they may be severer than the indication itself for their use and may be even fatal. The paper describes the adverse reactions observed in a female patient with SLE during long-term use of a high maintenance GC dose.

Despite a more than fifty-year period after the introduction of glucocorticoids (GCs) into therapeutic practice; they have headed the list of anti-inflammatory drugs so far. The paper analyzes current views on the terminology of GCs, mechanism of action, standardization of indications for their use in systemic lupus erythematosus, choice of a dose and a regimes of the drugs, as well as the rates of their decrease; the authors also review Russian and foreign literature on this problem and their own data.

The frequency of venous and arterial thromboses and plasminogen level have been investigated in 78 patients with the antiphospholipid syndrome (APS), including 35 patients with systemic lupus erythematosus (SLE + APS) and 43 patients with primary APS (PAPS). The levels and genotypes of plasminogen activator inhibitor type 1 (PAI-1) were determined in 45 patients with APS (21 patients with SLE + APS and 24 patients with PAPS). A control group included 10 individuals without autoimmune disease signs and thromboses during the observation period and in anamnesis. It has been shown for the first time that for one third of 67 patients with APS and thromboses, high-positive levels of antiphospholipid antibodies (aPL) are associated with low plasminogen levels. The levels of PAI-1 antigen measured by the ELISA method, which detects active, latent and bound to plasminogen activator PAI-1, were compared with frequency of thromboses in APS patients. In one third of 43 patients with APS and thromboses the high and increased levels of PAI-1 were associated with high-positive aPL levels. One of possible mechanisms of this interrelationship was considered. It was shown that arterial and, to a greater extent, venous thromboses are associated with the 4G/5G polymorphism of the PAI-1 gene and high plasma level of the inhibitor in 79% of APS patients. In the presence of the 4G allele SLE + APS patients had higher PAI-1 levels than PAPS patients. The data obtained show that measuring the levels of plasminogen and PAI-1 as well as the 4G/5G polymorphism of the PAI-1 gene associated with thromboses may have the practical importance for identification of high risk of thrombosis in APS patients.

Antifosfolipidnyi sindrom (AFS) – simptomo- kompleks, proyavlyayushchiisya trombozom sosudov razlichnoi lokalizatsii i kalibra pri obyazatel'nom nalichii v krovi antifosfolipidnykh antitel (aFL) [1]. K serologicheskim markeram AFS, soglasno mezhdunarodnym diagnosticheskim kriteriyam, otneseny: antitela k kardiolipinu (aKL) i/ili volchanochnyi antikoagulyant (VA), i/ili antitela k β2-glikoproteinu 1 (anti-β2-GP 1). V zavisimosti ot pozitivnosti po aFL rekomendovano stratifitsirovat' bol'nykh AFS po sleduyushchim kategoriyam: I – vyyavlenie bolee odnogo laboratornogo markera (v lyuboi kombinatsii); IIa – tol'ko VA; IIb – tol'ko aKL; IIc – tol'ko anti-β2-GP 1 [2]

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia diagnosed based on the presence of a single clinical sign (thrombosis or and obstetric problem) and one serological criterion (anticardiolipin antibodies and/or lupoid anticoagulant and/or antibodies against b2-glycoprotein-1. Clinical feature of the syndrome are diverse and depend on localization and diameter of the affected Bessel. This review focuses on cardiovascular aspects of APS. Cradiovascular system disorders are arbitrarily divided into valvular pathology, coronary and myocardial lesions. The relationship between antiphospholoipid antibodies and atherosclerosis is discussed.

The start of the new millennium is marked by a substantial progress in the development of rheumatology: pathogenesis of many rheumatic diseases (RDs) was more deeply studied; their diagnostic criteria validated; disease activity indices worked out; the concepts of remission and exacerbation introduced; much attention has been given to the investigations of quality of life in patients. The possibility of pharmacotherapy for immunoinflammatory RDs was extended by the advent of biological agents (BA). The treatment strategy for RDs was also changed. The treat-to-target concept was put forth for rheumatoid arthritis in 2010 and for ankylosing spondylitis later. The project of treat-to-target concept in systemic lupus erythematous (SLE) was launched on the initiative of the world’s leading rheumatologists in January 2013. The result of their work is the treat-to-target-in-SLE recommendations published in 2014 and formulated as 4 basic principles and 11 general recommendations. The purpose of this publication is to provide general characteristics of the basic provisions of the principles and recommendations with commentaries of leading experts discussing characteristics of SLE in the Russian Federation and some debatable and unsolved problems.