Введение. Вальпроевая кислота широко назначается в качестве противоэпилептического препарата и стабилизатора настроения. Несмотря на широту ее назначения, она имеет ряд побочных эффектов: усталость, тремор, седация, гепатотоксичность, увеличение веса, выпадение волос и тромбоцитопения. Лекарственно-индуцированная тромбоцитопения на фоне применения вальпроевой кислоты развивается при ее использовании в дозе более 1000 мг/сут, сопутствующем применении антиагрегантов, а также у пожилых пациентов. Данный побочный эффект обычно развивается в течение 1-2 недель после приема лекарственного средства, однако симптомы могут возникнуть и непосредственно после приема препарата. У пациентов наблюдаются петехии, экхимозы и пурпура, а также носовое кровотечение, гематурия, кровоточивость десен и гематохезия. Цель работы. Провести анализ и систематизацию литературных данных о причинах, механизме и частоте развития тромбоцитопении на препараты вальпроевой кислоты. Материалы и методы. Проведен анализ 42 отечественных и зарубежных публикаций по теме развития тромбоцитопении в ответ на препараты вальпроевой кислоты. Результаты. Частота развития тромбоцитопении в ответ на препараты вальпроевой кислоты составляет от 5% до 31% в общей выборке, до 54% у пожилых людей. Вальпроевая кислота оказывает прямое токсическое воздействие на костный мозг, что снижает выработку нейтрофильного и эритроидного ростков костного мозга посредством ингибирования дифференцировки эритроцитов и активации миеломоноцитарного пути. Помимо того, происходит включение вальпроевой кислоты в мембрану тромбоцитов вследствие структурного и химического сходства с жирными кислотами клеточных мембран. Это способствует выработке аутоантител, направленных против циркулирующих тромбоцитов, и приводит к усиленной деструкции тромбоцитов и тромбоцитопении. Заключение. Тромбоцитопения считается распространенным побочным эффектом при применении препаратов вальпро-евой кислоты, но все-таки вызывает меньший интерес в клинических исследованиях, несмотря на важные терапевтические последствия. Необходимы дальнейшие исследования, направленные на изучение данной проблемы. Background. Valproic acid is widely prescribed as an antiepileptic drug and mood stabilizer. Fatigue, tremor, sedation, hepatotoxicity, weight gain, hair loss and thrombocytopenia have been reported as side effects. Drug-induced thrombocytopenia occurs as the valproic acid dosage exceeds 1000 mg/day, or during concomitant antiplatelet agents administration, as well as in elderly patients. This side effect usually develops within 1-2 weeks after the drug initiation, but symptoms may also occur immediately after taking the drug. Patients present with petechiae, ecchymosis, and purpura, as well as epistaxis, hematuria, gingival bleeding, and hematochezia. Aim of the review. To analyze and systematize the literature data on the causes, mechanism and incidence of thrombocytopenia in response to valproic acid preparations. Materials and methods. An analysis of 42 domestic and foreign publications on the topic of thrombocytopenia due to valproic acid preparations was carried out. Results. The incidence of thrombocytopenia due to valproic acid drugs ranges from 5 to 31% in the general sample, up to 54% in elder people. Valproic acid has a direct toxic effect on the bone marrow, which reduces the production of neutrophil and erythroid lineages in the bone marrow through inhibition of erythrocyte differentiation and activation of the myelomonocytic pathway. In addition, valproic acid is incorporated into the platelet membrane due to its structural and chemical similarity to fatty acids in cell membranes. This promotes the production of autoantibodies directed against circulating platelets and leads to increased platelet destruction and thrombocytopenia. Conclusion. Thrombocytopenia is considered a common side effect of valproic acid drugs but has received less interest in clinical trials despite important therapeutic implications. Further research is needed to address this issue.

Introduction. ITGA2 gene C807T and ITGB3 gene T1565C polymorphisms influence the development of cardiovascular conditions and may worsen the condition of patients with COVID-19.The aim of this study was to evaluate the multimorbidity in COVID-19 patients with ITGA2 gene C807T and ITGB3 gene T1565C polymorphisms.Materials and methods. The case-control study was conducted: group 1 included 25 patients with COVID-19; group 2 — 25 patients with COVID-19 and acute coronary syndrome. The groups were adjusted by age, volume of lung lesions, body mass index, terms of hospital stay. The genetic study was performed on a DTprime (DT-96) detection amplifier.Results. In Group 1, chronic heart failure occurred in 6 CC patients of ITGA2 gene, 8 — with T allele; in Group 2 — 12 and 7 patients, respectively (p = 0.036). Previous acute myocardial infarction occurred in 1 CC patient, no persons with T allele; in Group 2 — 2 and 9 cases, respectively (p < 0.001). In Group 1, obesity occurred in 8 CC patients, 1 — with T allele; in Group 2 — 7 and 3 cases, respectively (p = 0.006). The ITGB3 gene polymorphism had no effect on the multimorbidity.Discussion. There is a close connection between the ITGA2 (C807T) polymorphism and the development of recurrent myocardial infarction and chronic heart failure against the background of the existing systemic inflammatory process, platelet hyperactivation and fibrosis.Conclusion. The data obtained indicate a significant influence of ITGA2 (C807T) gene polymorphism and the absence of an influence of ITGB3 (T1565C) gene polymorphism on the multimorbidity of patients with COVID-19.

Introduction. Platelets play an important role in arterial thrombosis, and the effects of SARS-CoV-2 on platelets contribute to an increased risk of thrombosis.Aim. To evaluate platelet link of hemostasis system and polymorbidity in patients with acute coronary syndrome and COVID-19 at the time of admission to the hospital.Materials and methods. The case-control study included 96 pairs of patients with acute coronary syndrome (ACS). The groups were adjusted by gender, age and diagnosis of ACS. Group 1 had ACS and COVID-19, Group 2 had ACS without COVID-19. Blood indicators were examined using the Mindray BC-5150 and ABX Micros-60 automatic hematology analyzers, the results of which were comparable Statistica 13.0 environment was used for statistical processing. The study was approved by the Local Ethics Committee of Ural State Medical University by Protocol No. 9 dated 10.22.2021.Results. Platelet level (PLT) was 242 (178÷299) x 109/L Group 1 and 236 (199÷291) x 109/L, in Group 2, p = 0.927. Mean platelet volume (MPV) was 10.0 (9.3÷11.5) fl in Group 1 and 8.0 (7.6÷8.8) fl, in Group 2, p < 0.001. Platelet distribution width (PDW) was 16.2 (15.9÷16.4) in Group 1, and 15.7 (14.7÷16.7) in Group 2, p < 0.001. Plateletcrit (PCT) was 0.24 (0.18÷0.30)% in Group 1 and 0.19 (0.16÷0.24)% in Group 2, p < 0.001. Platelet-to-lymphocyte ratio (PLR) 159.4 (109.5÷232.9) in Group 1 and 118.4 (88.2÷158.1) in Group 2, p < 0.001. The Charlson polymorbidity index in Group 1 was 5 (4÷6) points, in Group 2 – 4 (4÷6) points, p = 0.047.Conclusions. Higher PDW, MPV, PCT values with the same PLT, higher PLR level and higher polymorbidity at the time of hospitalization may indicate more pronounced platelet activation due to inflammation, severe immunosuppression and concomitant diseases in patients with COVID-19.

—An increase in the prevalence of different cognitive disorders, including Alzheimer’s disease (AD), determines the relevance of the search for methods for the early diagnosis of neurodegenerative diseases. Therefore, various peripheral biomarkers are actively studied for their later measurements by standardized methods available in real clinical practice. Due to the development of the hypothesis about the similarity of biochemical and physiological processes in platelets and neurons, increasing attention is paid to studying the possibility of using different structural and functional platelet parameters as biomarkers for different neurological diseases. This review discusses the main characteristics of platelets in the development of cognitive impairment; the peripheral aspects of amyloidogenesis and tau protein formation, changes in the synthesis and metabolism of active substances, and deregulation of microRNA, as well as the dysfunction of enzymes and proteins, were analyzed, which can be used to develop diagnostic tests for early detection of AD.

В обзоре анализируются современные представления о структурно-функциональных особенностях интегринов у человека; исследования связи между полиморфизмом гена T1565C, кодирующего интегрин бета‑3 (ITGβ3), тромботических явлений и эффективностью применяемых антитромбоцитарных препаратов; рассмотрена целесообразность исследования на наличие данного полиморфизма. Анализ проведен на основе публикаций, представленных в базах данных и web-ресурсах: MEDLINE, PubMed, Google Scholar, Cyberleninka, электронной библиотеке eLibrary, охватывающих временной период с 1989 по 2022 г. Критериями включения в обзор являлись статьи на русском и английском языках, результаты когортных и рандомизированных исследований, мета-анализов, систематические обзоры исследуемой проблемы, а также описания клинических случаев. Критериями исключения из выборки послужили исследования с отсутствием четко сформулированных выводов или наличием противоречивых результатов. This review describes the main modern provisions on the structural and functional features of integrins in humans; studies of the relationship between polymorphism of the T1565C gene encoding integrin beta 3 (ITGβ3), thrombotic events and the effectiveness of antiplatelet drugs used; the expediency of research for the presence of this polymorhism is considered. Data analysis was carried out on the basis of publications presented in databases and web resources: MEDLINE, PubMed, Google Scholar, Cyberleninka, eLibrary, covering the time period from 1989 to 2022. The inclusion criteria for the review were articles in Russian and English, results of cohort and randomized studies, meta-analyses, systematic reviews of the problem under study, as well as descriptions of clinical cases. Exclusion criteria were studies with no clear-cut conclusions or conflicting results.

A novel biologically active nanocomposite glycerohydrogel based on two biocompatible precursors, silicon and iron glycerolates, was synthesized by the sol-gel method in the presence of chitosan (Ch). The composition and structural features of the gel were characterized by advanced analytical methods including transmission electron microscopy, X-ray diffraction, and atomic emission spectroscopy. It was shown that iron(iii) monoglycerolate undergoes partial hydrolysis under the gelation conditions and exists as a separate nanoscale phase along with the hydrolysis products in cells of the 3D Si-containing polymeric gel network. This network is formed as a result of incomplete hydrolysis of silicon glycerolates in excess glycerol followed by homo- and heterofunctional condensation of silanol groups with the formation of Si-O-Si units containing residual glyceroxy groups at the silicon atom. Chitosan forms numerous intermolecular bonds with the 3D gel network, accelerates the process of gelation, makes the gel morphostructure more ordered, and increases the stability of the gel. The Si-Fe-Ch-containing glycerohydrogel is nontoxic and possesses hemostatic and wound-healing activity, being a promising topical medication for medical and veterinary practice.

В настоящее время в связи с прогрессированием старения населения наблюдается увеличение распространенности когнитивных нарушений различной этиологии. Продолжается активный поиск биомаркеров, которые могут быть использо­ваны в ежедневной клинической практике для ранней диагностики, играющей ключевую роль в разработке новых методов терапии и мониторинга заболеваний, проявляющихся когнитивной дисфункцией. Тромбоциты — безъядерные форменные элементы крови, играющие важную роль в гомеостазе и функционировании эндотелия сосудов, обладают схожим проте­омным составом с нейронами, что позволяет рассматривать их в качестве перспективных кандидатов для моделирования и оценки процессов нейродегенерации. В настоящее время активно исследуются возможности использования структурных и функциональных параметров тромбоцитов для диагностики когнитивных нарушений, в частности, болезни Альцгеймера. В данном обзоре проводится анализ возможного применения основных структурно-функциональных показателей тром­боцитов в качестве биомаркеров когнитивных нарушений. At present, cognitive disorders prevalence of various etiologies increase due to the progressive population aging. An active search continues for biomarkers to be used in daily clinical practice for early diagnosis of diseases manifested by cogni­tive dysfunction, which plays a key role in the development of new treatment and monitoring approaches. Platelets are nuclear-free blood cells with an important role in homeostasis and endothelium functioning. Moreover, platelets have a similar proteomic composition with neurons that allows to estimate them as promising candidates for modeling and evaluating the neurodegener­ative processes. Currently, the possibilities of using the structural and functional platelet parameters for the diagnosis of cognitive disorders, in particular, Alzheimer’s disease, are being actively investigated. This review analyzes the possible use of the main structural and functional platelet parameters as biomarkers of cognitive impairment.

The use of platelet-based biological materials attracts special attention in regenerative medicine. The aim of the work was to study the peculiarities of mechanical properties of the system «peri-implant bone tissue-implant» depending on the morphofunctional properties of platelets under conditions of titanium rod implantation into the femur bone of rabbits. The number of platelets, mean volume (MPV), thrombocrit, ratio of large platelets to their total number, and ADP-induced aggregation were determined. During mechanical testing, we determined the maximum load on the «peri-implant bone-implant» system and its elastic properties. According to the result of preoperative determination of the morphofunctional characteristics of the platelets, the rabbits were divided into 2 groups: low platelet potential (LTP) and high platelet potential (HPP). Determination of the mechanical parameters of the «peri-implant bone tissue-implant» system showed that the maximum load in the NTP group was lower than in the VTP group, at the same time, no significant differences were found in the parameter characterizing elasticity (Elastic). The number as well as the morphofunctional characteristics of the circulating platelets in the blood have a significant impact on the strength characteristics of the newly formed peri-implant bone tissue.

Новая коронавирусная инфекция (COVID-19), вызванная вирусом SARS-CоV-2, представляет собой опасность для многих органов и систем человека. Одной из таких систем является система гемостаза, особенностью поражения которой считается склонность к избыточному тромбообразованию и последующему возникновению тромботических осложнений. Уникальность коагулопатии при новой коронавирусной инфекции связана с повышением уровня фибриногена, D-димера и гиперактивации тромбоцитов за счет снижения количества тромбоцитов наряду с их повышенной деструкцией и снижением продукции. В обзоре приведен анализ публикаций, описывающих частоту, предполагаемые причины и патогенез наблюдаемых при COVID-19 тромбоцитопении и тромбообразования. Рассмотрено влияние новой коронавирусной инфекции непосредственно на функцию тромбоцитов, а также на высвобождение тромбоцитами биологически активных факторов. The novel coronavirus disease (COVID-19) caused by SARS-CoV-2 virus represents a danger to many human organs and systems, hemostasis is one of them. Characteristic feature of hemostasis lesion is the tendency to excessive thrombus formation and the subsequent occurrence of thrombotic complications. Coagulopathy uniqueness in novel coronavirus infection is associated with an increased level of fibrinogen, D-dimer and platelet hyperactivation due to a decrease in platelets number along with their increased destruction and reduced production. The review presents an analysis of publications describing the frequency, supposed reasons and pathogenesis of thrombocytopenia and thrombosis observed in COVID-19. Direct impact of novel coronavirus infection on platelet function as well as on the release of biologically active factors by platelets, is considered.

Introduction. Acute respiratory distress syndrome (ARDS) and cardiovascular events, acute myocardial injury being the most frequent of the latter, are among the leading causes of death in COVID-19 patients. The lack of consensus on acute myocardial injury pathogenesis mechanisms, the patients management, treatment an rehabilitation logistics, the anticoagulant treatment in identified SARS-CoV-2 or suspected COVID-19 patients setting indicates the need to assess, analyze and summarize the available data on the issue.Materials and methods. Scientific publications search was carried out in PubMed, Google Scholar databases for the period from December 2019 to September 2021.Results and Discussion. Cardiospecific troponin I increase beyond reference limits is reported to occur in at least every tenth patient with identified SARS-CoV-2, the elevated troponin detection rate increasing among persons with moderate to severe course of the infection. The mechanisms of acute myocardial injury in patients with COVID-19 are poorly understood. By September 2021, there are several pathogenesis theories. A high frequency viral myocarditis direct cardiomyocytes damage is explained by the high SARS-CoV-2 affinity to ACE2 expressed in the myocardium. The cytokine storm related myocardial damage is reported a multiple organ failure consequence. Coagulopathy may also trigger myocardial microvessels damage. Up to every third death of SARS-CoV-2 infected persons is related to the acute myocardial injury. At the same time, due to the high incidence of the acute myocardial injury, it is rather difficult to assess the true incidence of acute myocardial infarction in patients with COVID-19. In the pandemic setting, the waiting time for medical care increases, the population, trying to reduce social contacts, is less likely to seek medical help. In this regard, in order to provide effective medical care to patients with acute myocardial infarction, it is necessary to develop algorithms for providing care adapted to the current epidemiological situation.Conclusion. The treatment of patients with probable development of acute myocardial damage against the background of new coronavirus infection should be performed in accordance with the current clinical guidelines. Anticoagulant therapy should be administered in a prophylactic dose under control of hemostasis parameters and a wide range of biochemical parameters.

Background. The ceramic based on lanthanum zirconate is characterized by optimal mechanical characteristics, low corrosion potential and the absence of cytotoxicity. Thus, the possibility of its use as bone substituting material is currently studied.The purpose of the studywas to determine the mechanical, morphological and x-ray spectral characteristics of bone tissue after implantation of ceramic material based on lanthanum zirconate.Materials and methods. The experiment was conducted on 27 female guinea pigs of a single line, divided into 3 groups of 9 animals each. In the main group (LZ), lanthanum zirconate rods were implanted. In the comparison group (b-TCP), fixation was performed with b-tricalcium phosphate rods. In the native control group (NC) no surgical procedures were performed. A fracture was created in distal metadiaphysis area of femur using open osteoclasia. Animals were hatched 4, 10, and 25 weeks after the start of the experiment. Bone tissue features were studied in the perifocal region. The following methods were used: uniaxial compression, scanning electron microscopy (SEM), energy dispersive x-ray microanalysis (EDxMA). The statistical analysis was performed using the Mann-Whitney test.Results. The architectonics of the newly formed bone in the LZ group appeared as a developed lacunar tubular network. The structural components of the extracellular matrix were oriented along the bone functional load vectors. The Ca/P ratio in the periimplant region of the bone in the LZ group was significantly higher than in the b-TCP and NC groups. This may indicate a high strength of the newly formed bone. Mechanical testing showed that the strength and performance of the system of “lanthanum zirconate – bone” under uniaxial compression exceeded the similar indicators in the b-TCP group.Conclusion. The synthesized new material based on lanthanum zirconate seems promising for use in traumatology and orthopedics. Although, additional studies are needed to optimize these implants integration into bone tissue.

Обширные операции в ортопедии вызывают значительные изменения в системе гемостаза. Центральное место в регуляции гемокоагуляционных процессов занимает эндотелий сосудов. В обзоре рассматриваются механизмы, с помощью которых при повреждении сосуда формируется сгусток, эффективно закрывающий травмированный участок. Обсуждается роль эндотелия в развитии патологических тромбов при крупных ортопедических операциях. Extensive orthopedic operations cause signifi cant changes in hemostasis. The endothelium of blood vessels plays a central role in regulation of hemocoagulation processes. This review focuses on the mechanisms which form a clot in the case of vessel damage. The role of endothelium in the development of pathological blood clots in orthopedic surgery is discussed.

The large orthopedic operations are associated with high risk of development of thrombosis of deep veins of lower extremities. Nowadays, new oral anticoagulants are widely applied for anti-thrombotic prevention. The coagulation alterations against the background of effect of Dabigatran, a direct inhibitor of thrombin were examined in 30 patients underwent endoprosthesis replacement of knee joint. The routine clotting indices, fibrinopeptid A, soluble fibrin-monomeric complexes, D-dimer. The samples of blood were selected before operation, after 30 minutes, and at 1st, 3d, 7th and 14th day after endoprosthesis replacement of knee joint. It is demonstrated that routine clotting tests and also detection of D-dimer and soluble fibrin-monomeric complexes provide no adequate evaluation of coagulation activity in patients underwent large orthopedic operation. The concentration of specific marker of fibrin formation of fibrinopeptid A continues to be increased no less than two weeks after endoprosthesis replacement of knee joint that testifies keeping hyper-coagulation and risk of thrombosis. The intake of Dabigatran etexilate in fixed dosage does not exclude development of thrombosis of deep veins of lower extremities that substantiates point of view concerning usefulness of individualization of anti-thrombotic prevention in case of application of new oral anti-coagulants.

Thromboelastography (TEG) provides a means of monitoring coagulation postoperatively, the triggers involved are not clear. We studied the TEG parameters after total hip arthroplasty (THA), exploring the relationship with markers of hemostasis. In samples collected from 61 patients (33-72 years old), TEG parameters, global coagulation indices and specific hemostatic markers (TAT, D-dimer, and β-thromboglobulin) were assessed. Blood samples were taken before THA, 30 min after completion of surgery, and post-THA (Days 1, 3, 7, and 14). TAT levels peaked upon completion of THA, declining on Day 1 and normalizing by Day 3; β-thromboglobulin levels increased sharply to peak upon completion of THA, returning to baseline levels after Day 7; and the TEG coagulation index (CI) of whole blood increased immediately after THA, peaked within 7 days, and remained elevated for up to 14 days. After surgery (30 min), CI correlated significantly with platelet count (r=0.31, p<0.05) and β-thromboglobulin level (r=0.60, p<0.05). On postoperative Day 1, CI correlated with fibrinogen level (r=0.42, p<0.05) and platelet count (r=0.36, p<0.05). By Day 3, a correlation between CI and activity of the external coagulation pathway was noted. CI and PT also correlated significantly on Day 7 (r=-0.45, p<0.05) and Day 14 (r=-0.47, p<0.05). D-dimer concentration increased sharply at completion of surgery, declined at Day 3, rose again by Day 7, and remained elevated until Day14. On the other hand, the whole blood lysis index (Ly30) was unchanged at completion of surgery and during postoperative Day 1, increased significantly on Day 3, and then returned to baseline levels by Day 7. In conclusion, thrombin formation after major orthopedic surgery declines; but the total coagulation potential of blood (under standard anticoagulant treatment) peaks within one week and remains elevated at least until postoperative Day 14, correlating with activity of the external coagulation pathway during this time.

216 patients have been examined after total hip arthroplasty. Reliable parameters determining prethrombotic shifts in the thrombocytic and plasma elements of the hemostasis system in patients with thromboembolic complications (TEC) yet preoperatively were identified in the process of the study performed. The results obtained have given rise to the development of the treatment-and-diagnosis algorithm for TEC prevention in patients with dystrophic diseases of the hips subjected to arthroplasty. The clinical-amnestetic and laboratory data evidence that TEC belong to a pathological process of dystrophic nature.

The aim of the study was to investigate the influence of age on the character of changes in the hemostasis system dynamically in 77 patients underwent the large joint arthroplasty. The parameters of coagulation, fibrinolysis were analyzed, as well as anticoagulants. Slower recovery of the level of prothrombin complex factors has been revealed, as well as less marked reactive thrombocytosis, higher activity of fibrin formation and lysis, greater activity of PAI-I reflecting endothelial dysfunction in the postoperative period in elderly patients in comparison with middle-age patients. Conclusions. More intensive fibrin formation and more pronounced endothelium damage in elderly patients may increase the risk of postoperative deep-vein thrombosis in comparison with middle-age patients.

The prediction and diagnosis of thromboembolic complications in extensive orthopedic surgery pose a serious problem. Solving this problem becomes important in the study of the functioning of the hemostatic system. The study of the functioning hemostatic system is important for solving this problem. We investigated the effect of the pre-operative activity of fibrin formation and fibrinolysis on the dynamics of hemostasis, post primary hip or knee arthroplasty. This prospective study included 102 patients, segregated into two groups: The 1st group of 51 patients was characterized by the pre-operative activity of the formation of fibrin degradation products (D-dimer) in the normal range (<250ng/mL) with a mean value of 153 +/- 55 ng/mL; the 2nd group of 51 patients had an initial D-dimer concentration above the norm, with a mean value of 470 +/- 201 ng/mL. Otherwise, the groups were equal with respect to gender, localization of the operated segment, and type of anesthesia. This study was performed prior to surgery, and days 1, 3, 7, 14, post arthroplasty. The coagulation parameters, fibrinolysis, and physiological anticoagulants were determined. Patients of the 2nd group were older than the patients of the 1st group: 51.7 +/- 9.7 years vs. 57.0 +/- 10.7 years, p<0.05. In the 2nd group, patients with higher initial levels of fibrin formation and lysis, showed retention of higher D-dimer concentrations after day 1 post surgery (1,447 +/- 478 ng/mL vs 1,202 +/- 594 ng/mL in the 1st group, p<0.05) and after day 3, post surgery. However, by day 7, the differences were leveled. No significant differences in the TAT, plasminogen and PAI-1 levels were observed during the entire study. No significant differences were noted in the number of verified thromboses of the deep veins, which was 17.5% in the 1st group and 16.1% in the 2nd group. The initial increase in the degree of fibrin formation and fibrinolysis did not raise the risk of thromboembolic complications during hip and knee arthroplasty. IJBM 2012; 2(3): 186-191. (C) 2012 International Medical Research and Development Corporation. All rights reserved.