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Aim. To assess the compliance of nephroprotective and anticoagulant therapy in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) with modern clinical guidelines.Material and methods. The study included patients with CKD in combination with AF and in sinus rhythm. Clinical characteristics were retrospectively assessed, as were the use of renin-angiotensin system inhibitors (RASi), statins, sodium-glucose transporter type 2 inhibitors (SGLT-2i) and oral anticoagulants (OAC).Results. A total of 464 patients (aged 66-80 years) were divided retrospectively in two subgroups — with and without AF. AF was detected in 210 (45.3%) patients. Patients from the subgroup with AF were significantly older (75 vs 72 years, p=0.001), more often had type 2 diabetes mellitus (T2DM) (28.6% vs 20.5%, p=0.042), coronary artery disease (CAD) (40.5% vs 30.7%, p=0.028) and chronic heart failure (CHF). (57.6% vs 22.8%, p

The aim. To analyze arrhythmological complications in cardiac surgery patients with coronary artery disease (CAD). Materials and methods. This was a retrospective data analysis of 354 cardiac surgery patients with various forms of CAD who were operated on and discharged from the National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine. The mean age of the patients was 61.9 ± 9.6 years. All the patients underwent laboratory examinations, electrocardiography, echocardiography, coronary angiography and cardiac surgery. The patients with uncomplicated forms of CAD (n = 194) underwent isolated surgical revascularization of the myocardium, in the case of complicated forms of CAD (n = 160), coronary bypass surgery was supplemented with valvular or ventricular correction. Results. Postoperative atrial fibrillation (AF) occurred in 40 (20.6%) patients with uncomplicated CAD and 43 patients with complicated CAD (26.8%), p = 0.1667. Among patients with complicated forms of CAD, 2 (1.25%) had paroxysms of ventricular tachycardia, which required the implantation of a cardioverter-defibrillator, also in this group of patients complete left bundle branch block occurred more often (p = 0.0020). The postoperative period in patients with impaired glucose metabolism was characterized by more frequent development of AF in patients with type 2 diabetes mellitus (33.3%, p = 0.0006), with impaired glucose tolerance (24.8%, p = 0.0156) compared to patients with normoglycemia (12.6%). Conclusions. There was no statistically significant difference in the frequency of postoperative AF in patients with various forms of CAD (p = 0.1667). In the occurrence of postoperative AF paroxysms, the negative influence of type 2 diabetes mellitus (p = 0.0006), impaired glucose tolerance (p = 0.0156), stage III-IV chronic kidney disease (p = 0.0015) and gouty arthritis (p = 0.0072) has been proven. The presence of postoperative AF was associated with acute encephalopathy (p = 0.0291) and panic attacks (p = 0.0043). The occurrence of postoperative AF increased the length of stay of cardiac surgery patients with CAD in the hospital from 8.2 ± 2.9 to 11.06 ± 6.8 days (p < 0.0001).

Background. Medication errors can cause preventable adverse events. For example, inappropriate use of anticoagulants (AC) can result in bleeding and thromboembolic complications. Detection and analysis of AC medication errors allow to reveal deficiencies in the safety systems in healthcare organizations. Aim. The study was aimed to develop a method of systematic detection of anticoagulant medication errors for consequent audit, analysis and development of medication safety improvement measures. Materials and methods. The study was conducted in the multidisciplinary hospital and included 4924 patients admitted from January 2019 to December 2021 who received AC. Three laboratory triggers (international normalized ratio ≥4, serum creatinine ≥133 μmol/l, and glomerulofiltration rate 30 ml/min/1.73 m2) helped to reveal 4304 cases. Their matching with patient’s data helped to develop combined triggers. Two clinical pharmacologists reviewed all cases identified by combined triggers for checking medication errors. The trigger was considered positive when anticoagulant medication error was detected in the history selected by combined trigger. Results. Of the 4924 patients 253 (5.3%) were selected by combined triggers. Combined trigger allowed to reduce the amount of medical health records audit by 97.3%. Medication errors were detected in 137 patients. Positive predictive value of selected combined triggers varied from 0 to 63.9%. Aggregated positive predictive value of all combined triggers amounted to 54.2%. AC medication errors were detected in 2.8% patients. Conclusion. Method of systematic detection of AC medication errors using combined triggers in all hospitalized patients receiving AC allowed to reveal typical medication errors for consequent analysis and elaboration of measures to reduce preventable patient harm in healthcare settings.

In most cases, portal vein thrombosis progresses without treatment; spontaneous recanalization of portal vein develops in 42 % of patients with liver cirrhosis. Effective treatment strategies include administration of anticoagulants, interventional procedures such as transjugular intrahepatic porto-systemic shunt or endovascular fibrinolysis. Anticoagulant therapy has certain difficulties in patients with liver cirrhosis due to the complex profile of hemostasis, a tendency to both hemorrhages and hypercoagulation. In addition to traditional anticoagulants (heparin preparations, fondaparinux, vitamin K antagonists), direct oral anticoagulants have been widely used in recent years for portal vein thrombosis. Previously, portal vein thrombosis was considered a contraindication to performing transjugular intrahepatic porto-systemic shunt, currently the method is often used to restore portal blood flow through the shunt and prevent repeated thrombosis. Endovascular fibrinolysis is still an option for specialized centers for «difficult» patients. In cases of increased risk of venous thromboembolism, patients with liver cirrhosis are recommended to be prevented with low-molecular-weight heparin or direct oral anticoagulants, but further studies should clarify their effectiveness in this aspect. The review highlights data on the features of therapy, primary and secondary prevention of portal vein thrombosis in patients with liver cirrhosis. Despite the existing clinical recommendations for management of patients with cirrhotic portal vein thrombosis, the choice of a particular strategy primarily depends on an individualized assessment of risks and benefits of each treatment method.

Cardiotoxicity is the direct adverse effect of anticancer agents on the function or structure of the heart, occurring both during treatment and many years later. The manifestations of cardiotoxicity can be very different: heart failure, coronary heart disease, cardiomyopathy, myocarditis, pericarditis, and arrhythmias, including atrial fibrillation (AF). The incidence of AF in the cancer patient population during therapy is 20–30%. Current options of remote electrocardiogram monitoring ensure the timely detection and treatment of AF in cancer patients, including the administration of anticoagulants. The article presents a clinical case of a 59-year-old patient with squamous cell carcinoma of the lower third of the esophagus after the first course of the TPF polychemotherapy regimen (docetaxel, cisplatin, 5-fluorouracil) with AF detected using a single-channel electrocardiogram monitor in a smartphone case.

Introduction. Apixaban is an anticoagulant used in a number of thromboembolic diseases with an improved benefit-to-risk ratio, according to multiple clinical studies. Due to the prescription of apixaban as antithrombotic therapy in patients with COVID-19, an increase in its use has been observed. Thus, due to the widespread use of apixaban and the need to conduct pharmacokinetic and bioequivalence studies of the drug, it is important to develop and validate a simple and sensitive method for the quantitative determination of apixaban in human blood plasma.Aim. The aim of the study is to develop and validate a method for the determination of apixaban in human blood plasma using high-performance liquid chromatography with tandem mass selective detection (HPLC-MS/MS) for the subsequent bioanalytical study.Materials and methods. The determination of apixaban in human plasma was carried out by HPLC-MS/MS with rivaroxaban as an internal standard. The method of protein precipitation with acetonitrile was used as sample preparation. Mobile phase: 0.1 % solution of formic acid in water (eluent A); 0.1 % solution of formic acid in acetonitrile (eluent B). The total run time was 3.00 min. Column: Shim-pack Velox Biphenyl; 2.7 µm; 50 × 2.1 mm. Ionization source: electrospray with positive ionization mode. MRM transitions: 460.15 → 443.10 m/z (apixaban); 436.05 → 144.95 m/z (rivaroxaban).Results and discussion. The developed method was validated in accordance with the EAEU requirements for the following parameters: selectivity, calibration curve, accuracy and precision, lower limit of quantitation, suitability of standard samples, matrix effect, recovery, stability, carry-over, dilution effects. The parameters met the acceptance criteria.Conclusion. The confirmed analytical range of the developed and validated method was 1.00–300.00 ng/mL in blood plasma. The method for determining apixaban in blood plasma is simple and sensitive. This method was tested during the analytical part of the bioanalytical study and can be used to conduct other pharmacokinetic studies of apixaban drugs.

Venous thromboembolic events (VTE and ТЕ) in cancer are a complex and multicomponent process involving various non-modifiable and modifiable factors that increase or reduce the risk of abnormal thrombus formation. The paradigm of prevention and treatment of VTE in cancer patients has significantly changed with the introduction of new oral anticoagulants; however, the choice of a particular agent remains challenging for practitioners. This review aims to address the VTE development mechanisms in cancer patients, compare different scales in predicting VTE occurrence, and compare the effectiveness and tolerability of anticoagulant therapy in various clinical situations.

In the modern world, oncological diseases occupy the leading positions in the structure of mortality. An integrated approach to oncotherapy is not only aimed at immediate affection of malignant tumors, but also directed at reducing the risk of tumor recurrence and metastasis, as well as alleviating side effects of chemotherapy and radiotherapy of the disease. In oncologic disorders, blood viscosity increases, thus being associated with hypercoagulation syndrome. To prevent its consequences, the direct and indirect anticoagulants, especially heparin and its derivatives, are actively used. Biological functions and structural features of heparin make it a potential universal platform of a drug development for broad application, including oncology. With the advent of heparin fractionation technology and preparation of low-molecular weight forms and their derivatives, it has become possible to focus not only on anticoagulant activity but also to obtain fractions with targeted pharmacological activity. Usage of the anticoagulants has shown their antitumor activity in some cases, thus providing a basis for a more detailed study of pharmacotherapeutic effects of this group of drugs. Currently, some data suggest various pathways of interaction between heparin and tumor cells. There are multiple common features in development of a primary tumor and formation of secondary distant metastases, which may be attributed to similar molecular cellular mechanisms. The molecules mediating intercellular interactions, both between the tumor cells and between malignant cells and tumor-associated immune cells (e.g., lymphocytes and macrophages) may serve as targets for heparin thus helping the tumor to evade immune surveillance. The cytokines that stimulate tumor angiogenesis represent another important therapeutic target. Heparin derivatives are able to suppress tumor activity and prevent metastatic processes at various stages by inhibiting heparanase, P-/L-selectin, and angiogenesis activity, modulating the CXCL12-CXCR4 chemokine axis, and regulating OAM activity.This brief review addresses the current understanding and application of the potentially antimetastatic properties of heparin and its derivatives in malignant bone tumors since the heparin-based drugs are used as anticoagulants in arthroplasty of large joints and bone defects in patients with osteosarcoma.

After heart valve surgery, anticoagulant therapy is usually recommended. The duration and necessity of combining oral anticoagulants with antiplatelet drugs depends on the type of manipulation performed, patient comorbidity and some other factors. Several randomized trials have shown that continued direct oral anticoagulation as monotherapy in some groups of patients requiring cardiac surgery is superior in efficacy and safety to treatment combining anticoagulant and antiplatelet drugs. The presented literature review reflects the management strategy of patients after heart valve operations.

Non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) are important pharmaceuticals for prevention of stroke and systemic embolism in non-valvular atrial fibrillation patients. Vitamin K antagonist warfarin usage is limited due to its pharmacokinetic and pharmacodynamic parameters. In modern conditions, NOACs are widely used. This literature review includes the most interesting clinical studies where anticoagulants were used. Main pharmacological properties of non-vitamin K antagonist oral anticoagulants have been investigated in these clinical studies. The aim. To answer the question about which anticoagulant is preferable for use in particular clinical situation. Results. In order to prevent venous thrombosis, conservative and surgical treatment is used. It is the use of anticoagulants during conservative therapy that allows to extend the life expectancy of patients at high risk of thrombosis. Unlike warfarin, the use of NOACs helps to avoid high risk of bleeding. Drugs of this group have short half-life, standard dosage, and predicted pharmacological effect. Conclusions. New data about comparative efficacy and safety of treatment with NOACs (dabigatran, rivaroxaban, edoxaban, apixaban) in order to prevent thromboembolism in patients with atrial fibrillation are presented. The peculiarities of anticoagulant therapy in elderly patients, patients with coronary artery disease, atrial fibrillation, chronic kidney disease, patients in pre- and postoperative periods are discussed. Prolonged study of drugs of this group will enable doctors to use them without endangering the patients’ lives. NOACs, despite obtained data about their effectiveness and safety, in our opinion, deserve attention and require further study.

Antithrombotic drugs (antiplatelet agents and anticoagulants) are widely used in cardiological practice for primary and secondary prevention of thrombotic/thromboembolic complications, however, the use of such drugs is associated with the increased risk of hemorrhagic complications, including gastrointestinal hemorrhage. Assessment by video capsule endoscopy has shown that the damaging effects of antithrombotic drugs are not confined to the upper gastrointestinal mucosa, but also expand to the lower gastrointestinal tract, affecting small and large intestine. That is why it is reasonable to use rebamipide, the unique drug combining gastroprotective and enteroprotective effects, to protect gastrointestinal mucosa and prevent gastrointestinal hemorrhage. The drug exerts its effects at all three structural levels of the mucous membrane throughout the gastrointestinal tract; its efficacy and safety have been confirmed by multiple randomized clinical trials.

Background. Patients with hemophilia are protected from thrombosis by a deficiency of one of coagulation factors, therefore thrombotic complications are rare in them. Currently, few descriptions of spontaneous venous thrombosis in adult hemophiliacs can be found in the literature. Even fewer data of thromboembolic complications are reported in pediatric practice. At present, no clear recommendations are given for the management of thrombotic complications in children with hemophilia, which requires further study of this issue to develop prevention and treatment regimens, including otogenic sinus thrombosis in this category of patients.Case description. A 7-year-old boy was transferred from the Somatic Hospital to the Intensive Care Unit of Regional Clinical Hospital No. 2 in Tyumen (Russia) with an Otorhinolaryngology Unit. He was diagnosed with non-perforative form of acute right-sided suppurative otitis media, acute right-sided mastoiditis, thrombosis of the right sigmoid sinus. The anamnesis shows that the child is diagnosed with hemophilia A, of moderate severity (factor VIII level — 5%), for which he has been receiving factor VIII replacement therapy for the last year. Upon admission, a general blood test revealed no abnormalities, with a slight increase in acute-phase parameters: C-reactive protein, fibrinogen, signs of hypocoagulation. Due to negative dynamics, the child underwent anthromastoidotomy against the background of intensive replacement therapy. Surgery revealed the presence of granulation tissue with hemorrhagic thrombi in the antrum and aditus. In the postoperative period, replacement therapy was accompanied with antibacterial and anticoagulant therapy.Conclusion. The management of patients with otogenic sinus thrombosis against the background of hereditary factor VIII deficiency is a difficult task. On the one hand, it requires surgical intervention and anticoagulant therapy in order to prevent further thrombosis, on the other hand — intensive replacement therapy in order to reduce the risks of hemorrhagic complications. The described case demonstrates the need for an interdisciplinary approach to the diagnosis and treatment of a patient with otogenic thrombosis of lateral sinus against the background of hemophilia A. The approach is to minimize the risks of intraoperative complications and insure a favorable outcome.

Atrial fibrillation (AF) is one of the most common types of arrhythmias and represents a significant health and economic burden worldwide. Along with the aging of the population, there has been a rapid increase in the prevalence and incidence of AF. Among adults over the age of 55, one in three is expected to be diagnosed with AF during their lifetime. However, due to the fact that some patients do not experience symptoms associated with arrhythmia, unfortunately, all too often AF remains undiagnosed and untreated. Detection of asymptomatic and/or previously unknown AF is one of the key tasks of outpatient care, and considering that prevention of cardiovascular disease and cardiovascular complications is considered an important part of the work of general practitioners, this article will review pathophysiological mechanisms of AF, risk factors and diagnostic criteria of AF, and discuss algorithms of management tactics for patients with AF, which may be useful for routine clinical activities of the general practitioner.

The specifics of the anticoagulant therapy after radiofrequency ablation of the cavotricuspid isthmus have not been sufficiently studied, therefore, the recommendations for prescribing the anticoagulant therapy usually do not distinguish between atrial flutter and atrial fibrillation. In contrast to the case of atrial fibrillation, the effectiveness of the interventional treatment for typical atrial flutter reaches 90%. This procedure may save the patient from a long-term anticoagulant therapy in the absence of recurrence of typical atrial flutter. The decision to stop the anticoagulant therapy after successful radiofrequency ablation of the cavotricuspid isthmus should take into account the potential induction of atrial fibrillation in patients undergoing the interventional treatment. In addition to the CHA2DS2-VASc scale, which characterizes the patient's comorbidity, it is important to take into account the echocardiographic morphofunctional criteria to assess the risk of atrial fibrillation. Currently, this protocol is not regulated in the clinical guidelines. The analysis of the literature data and the authors' own experience allow us to conclude that the optimal time for stopping the anticoagulant therapy is a relapse-free period of 34 months after the radiofrequency ablation of the cavotricuspid isthmus, since it is at this time that the effectiveness of the interventional treatment can be objectified.

The review article discusses the issues of anticoagulant therapy in cardiovascular patients with thrombocytopenia (TP), gives the concept of ethylenediaminetetraacetic acidand heparin-induced TP. The management of patients with heparin-induced TP is analyzed in detail, which consists in the discontinuation of unfractionated and low molecular weight heparin administration with replacement to direct thrombin inhibitors (lepirudin or argatroban), fondaparinux or direct oral anticoagulants.The authors emphasize that the anticoagulant administration to most patients with platelet count >50×109/l is possible in full prophylactic and therapeutic doses. Reducing the level of platelets to 25-50×109/l in most cases requires a reduction in the anticoagulant dose by 50%. At a platelet level of 20-25×109/l or less, anticoagulant therapy should be avoided in most patients.In addition to the scope of anticoagulant therapy, TP also determines the choice of anticoagulant as follows: in patients with acute coronary syndrome, bivalirudin or fondaparinux are recommended, while in patients with cancer and stable TP, warfarin or direct oral anticoagulants can be prescribed. In progressive TP (if heparin-induced TP is ruled out), low molecular weight heparins should be used.

Left ventricular thrombus (LVT) is a serious risk factor for systemic embolism development. Despite the evident danger of this condition, current guidelines describe management of patients with this potentially fatal complication very briefly. LVT can complicate myocardial infarction where its incidence is around 10%, as well as various forms of cardiomyopathies and novel coronavirus infection. According to clinical guidelines vitamin K antagonists (VKAs) should be used as treatment of choice for thrombus resolution. However, experts point out that this therapy lacks necessary evidential base and bears certain difficulties because of pharmacokinetic and pharmacodynamical properties of VKAs. These drawbacks are absent in direct oral anticoagulants (DOACs), the possibility of using which in LVT is being actively studied. As for now, published results of 3 randomised clinical trials have demonstrated similar safety and efficacy profiles of DOACs and VKAs. Similarly, the majority of retrospective cohort studies did not observe significant differences between two groups, where some of them have shown superiority of DOACs especially in terms of earlier thrombus resolution. Nevertheless, some studies have found DOACs ineffective and even potentially unsafe regarding systemic embolism. Existing data does not allow to form an unambiguous conclusion about the equivalence of DOACs and VKAs for LVT resolution. Large randomised clinical trials are needed to determine efficacy and safety of such treatment in these patients.

Recently, there have been published the data of large randomized trials on the use of antithrombotic agents for reducing a risk of thromboembolic complications, multiple organ failure and mortality in COVID-19 patients. However, principles of selecting optimal therapy remain open. Strategies for the use of antithrombotic drugs in outpatient and inpatient settings, thromboprophylaxis in specific patient populations, and treatment of acute thrombosis in hospitalized COVID-19 patients are being developed. In October 2021, the International Society on Thrombosis and Hemostasis (ISTH) formed an interdisciplinary international panel of experts to develop recommendations for use of anticoagulants and antiplatelet agents in COVID-19 patients. Expert opinions are published. Here, we summarize all the publications available globally at the present time on this issue, obtained by using the principles of evidence-based medicine.

Due to the continued risk of recurrence after a first episode of proximal deep vein thrombosis (DVT) of the lower extremities and/ or pulmonary embolism (PE) occurring without major transient risk factors, long-term use of anticoagulants is indicated in many cases. One attractive way to individualize the duration of treatment in these cases appears to be the assessment of blood D-dimer concentration. However, according to the prospective studies PROLONG, PROLONG II and REVERSE II, even persistent normalization of blood D-dimer concentration does not guarantee the absence of relapse. The available evidence also does not allow a differentiated approach to the assessment of the role of D-dimer for cases where proximal DVT and/or PE occurs in patients without identifiable risk factors or with minor risk factors. An attempt to clarify some of these uncertainties was made in the prospective APIDULCIS study, which included 732 patients who first had proximal DVT and/or PE, with symptoms occurring in the absence of obvious provoking factors (75.6% of cases) or associated with minor (weak) and transient risk factors (24.4%). The prerequisites included a normal blood D-dimer concentration. Patients were discontinued anticoagulants and blood D-dimer concentration measurements were repeated after 15, 30, and 60 days. If it remained low, the anticoagulant was not resumed (39.1% of cases), and when it first increased, apixaban was administered in a dose of 2.5 mg twice daily. The APIDULCIS study confirmed that anticoagulants cannot be discontinued after 1 year of use after the first unprovoked episode of proximal DVT and/or PE, even with persistent normal blood D-dimer concentration; it was shown that recurrence rate after the first episode of proximal DVT and/or PE, provoked by a minor transient risk factor, is high enough even after at least 1 year of anticoagulant treatment and at stable normal blood D-dimer concentration after their cancellation; comfirmed the effectiveness and safety of a reduced dose of apixaban (2.5 mg 2 times a day) during prolonged treatment of the first episode of proximal DVT and/or PE.

The study objective is to demonstrate a rare cause of recurrent acute cerebrovascular diseases in a young patient – Sneddon syndrome. The patient revealed gene polymorphism: homozygous 4G/5G in the plasminogen activator inhibitor-1 (PAI-1) gene, C807T in the glycoprotein I gene (GPIa), T1565C in the glycoprotein III gene (GPIIIa), G1639A in the vitamin K epoxide reductase gene (VKORC1), increased homocysteine, which were risk factors for thrombosis.

Intracranial hemorrhage (ICH) is characterized by a high level of disability and mortality. One of the most important reasons that lead to an increased risk and an increase in the ICH prevalence are antithrombotic drugs: anticoagulant, antiplatelet and thrombolytic. The main risk factors for ICH are advanced age, arterial hypertension, and the use of antithrombotic drugs of different groups. Treatment of ICH while taking drugs affecting hemostasis, is an extremely difficult task and there is not enough sufficiently convincing recommendations and evidence. The decision to resume therapy with the drug, that led to the development of ICH, and the timing of this resumption, is also not a completely clear problem that requires a balance between ischemic and hemorrhagic complications. The most important aspect of prevention is strict adherence to current recommendations regarding combinations of antithrombotic drugs and protocols for thrombolytic therapy, which will minimize the risks of ICH.

The aim. In the treatment of venous thromboembolism, a special place is occupied by patients with congenital anomalies of the development of the inferior vena cava (IVC). To date, only single cases of treatment of this pathology have been described in the literature. Studying the experience of treating patients with congenital anomalies of the IVC will allow to improve the results of treatment of this category of patients. Materials and methods. Patient B., a 36-year-old man, applied to the vascular surgery clinic of the Vinnytsia Regional Pyrohov Clinical Hospital in July 2010 with complaints of pain, swelling, cyanosis of both lower extremities, which bothered the patient for about 10 days. The patient had no history of venous insufficiency of both lower extremities. An objective examination revealed cyanosis and swelling of both lower extremities. A duplex scan of both lower extremities revealed hyperechoic iliofemoral thrombosis of both lower extremities. Aplasia of the IVC was diagnosed. The common iliac veins on both sides formed a collateral that flowed into the left renal vein. The infrarenal segment of the inferior vena cava was absent. Thrombosis spread from tibial to popliteal, femoral, iliac veins with venous collateral thrombosis up to the level of the left renal vein. The patient received enoxaparin at a dose of 1 mg per kg of body weight twice a day for 7 days with subsequent transition to warfarin under the control of international normalized ratio. Warfarin was prescribed from a starting dose of 5 mg with subsequent control of international normalized ratio in the range of 2.0-3.0. Venotonic and anti-inflammatory drugs were also prescribed. In combination with drug therapy, class 2 elastic compression stockings were recommended. After the treatment, the patient’s condition improved, swelling and cyanosis of both lower extremities regressed. Repeated duplex scanning at the discharge of the patient from the hospital after 7 days showed signs of initial recanalization of the affected venous segments and no progression of thrombosis. Conclusions. Thus, this clinical case showed that the use of anticoagulant therapy allows to obtain satisfactory results in the treatment of patients with congenital anomalies of the development of IVC, to avoid the development of pulmonary embolism and other life-threatening conditions. At the same time, such patients need regular follow-up examinations in order to adjust the treatment and prevent the development of IVC syndrome.

Introduction. In recent years, data have been accumulated regarding possible associations between cognitive impairment and atrial fibrillation. The results of retrospective and prospective studies confirm that anticoagulant therapy in patients with AF can reduce the risk of cognitive impairment and dementia.Objective. To study the individual characteristics of elderly and senile patients with atrial fibrillation, influencing the choice of anticoagulant therapy, with a view to its subsequent optimization.Materials and methods. The study included 159 patients with atrial fibrillation of non-valvular genesis aged over 60 years. 4 groups of patients were formed. The largest number of patients received rivaroxaban and warfarin (36.4% and 34.6%, respectively). 26 (16.3%) patients were treated with dabigatran, 20 (12.6%) patients with apixaban. The risk of thromboembolic complications was assessed on the CHA2DS2-VASc scale. The HAS-BLED scale was used to assess the risk of bleeding. A pharmacogenetic study (carriage of polymorphic alleles of the CYP2C9 and VCORC1 genes) was conducted in 138 patients. Cognitive impairment was assessed by a Mini-Cog test and a battery of frontal tests.Results. Taking oral anticoagulants reduces the risk of stroke and dementia in patients; the presence of cognitive impairment, in turn, significantly reduces the patient’s adherence to therapy and reduces the effectiveness of therapy. Patients’ adherence to therapy was significantly lower by 10–20% in patients with cognitive impairment according to the Mini-Cog test and a battery of frontal tests. In the absence of pronounced cognitive impairment (higher adherence to treatment) and availability and willingness to control INR, warfarin remains the drug of choice in patients with renal insufficiency.Conclusions. A number of problems with the use of oral anticoagulants in elderly patients with atrial fibrillation have been identified. The ease of use of new oral anticoagulants, the absence of the need to select doses and monitor therapy is an important factor when choosing a drug.

The objective of our study was to determine the reasons for not prescribing anticoagulant therapy (ACT) in the therapeutic department of university clinic for patients with atrial fibrillation (AF) and a high risk of stroke and to discuss the optimal management of these patients.Methods and materials. A retrospective analysis of 1307 case histories of AF patients admitted to a university therapeutic clinic from 2014 to 2018 presented. The reasons for not prescribing ACT to patients with AF and high risk of stroke and optimal ACT discussed.Results. ACT was not prescribed to 109 (9.7 %) hospitalized patients out of 1128 patients with AF without prosthetic valves and mitral stenosis who had a high risk of stroke ((4.5±1.1) points on the CHA2DS2VASc scale). The risk of bleeding – (1.6±0.1) (HAS-BLED). The age of patients was (73.8±10.4) years. From 2014 to 2018, the frequency of unjustified non-prescribing ACT decreased by 3.7 times – from 47/205 (22.9 %) in 2014 to 11/178 (6.2 %) in 2018 (p=0.001). In general, over 5 years of observations, subjective reasons for not prescribing ACT were: lack of stroke risk assessment (78.0 %), senile age of patients and the presence of dementia (42.2 %), the first paroxysm of AF (22.9 %) during myocardial infarction and heart surgery, planned surgical treatment, effective radiofrequency ablation and patient refusal. Objective (usually transient) reasons for not prescribing ACT were: severe and moderate anemia (24.8 %), recent bleeding (11.9 %), gastrointestinal diseases predisposing to bleedings (9.2 %), oncology (12.8 %), end-stage chronic kidney disease (2.8 %), thrombocytopenia (2.8 %). Often various reasons for not prescribing ACT were combined.Conclusion. In patients with AF and a high risk of stroke, the incidence of not prescribing ACT decreased by 3.7 times from 2014 to 2018. In 2014, the most common reasons for not prescribing ACT were the lack of stroke risk assessment and the senile age of patients, and in 2017–2018 senile age, the first paroxysm of AF, effective radiofrequency ablation, anemia, recent bleeding, and gastrointestinal diseases predisposing to bleedings.

These days, anticoagulants are in great demand. They are used as a prophylaxis for thromboembolic complications in various diseases and conditions in general therapeutic practice, cardiology, neurology, as well as obstetrics to manage high-risk pregnancies. The relevance of anticoagulants competent use has come to the fore in connection with the emergence of a new disease – COVID-19 and its serious complications such as developing thrombotic storm, in which the timely applied anticoagulant therapy is the key to the success of therapy. The risk of bleeding should be considered when using any anticoagulant. Age, impaired renal function and concomitant use of antiplatelet agents are common risk factors for bleeding. Moreover, only vitamin K antagonists and heparin have specific antidotes – vitamin K and protamine, respectively. Inhibitors of other anticoagulants are universal presented as inactivated or activated prothrombin complex concentrate and recombinant factor VIIa. Hemodialysis effectively reduces dabigatran concentration, activated charcoal is effective in the case of recent oral administration of lipophilic drugs. Research on new antidotes of currently available anticoagulants is under way, similar to testing of new types of anticoagulants that are sufficiently effective in preventing and treating thromboembolic complications with minimal risk of hemorrhagic. The main contraindication to anticoagulants use is the doctor's ignorance of the mechanisms of drug action and opportunities for suppressing its effect.

Introduction Avascular necrosis of the femoral head is a debilitating disease affecting people of working age and having an important medical and social role. Total hip arthroplasty is the only effective treatment for late stages of necrosis. Various joint-preserving operations and non-surgical methods can be successfully used for less severe types. There is no unequivocal opinion on the effectiveness of various conservative treatments offered for avascular necrosis of the femoral head. The aim was to summarize data on the role of medications and physiotherapy in treatment of avascular necrosis of the femoral head through the analysis of the modern world literature. Material and methods The original literature search was conducted on key resources including elibrary, PubMed and ResearchGate. Results Outcomes of avascular necrosis of the femoral head treated conservatively were overviewed. The effectiveness of various treatments using bisphosphonates, anticoagulants, statins, prostacyclin derivatives was evaluated. Physiotherapy with shock wave therapy, pulsating electromagnetic fields, and hyperbaric oxygenation was also reviewed. Conservative treatment is reported to be effective only for early (pre-collapse) stages of avascular necrosis of the femoral head. Conclusions A conservative treatment used as a monotherapy for AVN cannot be assessed as a standalone procedure because various combinations of comprehensive treatment are used for the majority of patients. There are no studies in the literature comparing the effectiveness of conservative therapies using iloprost and statins, bisphosphonates and anticoagulants, shockwave and hyperbaric oxygen therapy in homogeneous patient samples. A deeper study of the underlying pathogenesis of avascular necrosis of the femoral head is required to develop personalized treatment strategies.

Cancer-associated venous thromboembolic complications are one of the main topical problems in the system of practical healthcare. Having overlapping pathogenetic mechanisms of development, thromboembolic complications accompany the oncological process and often act as its manifesting sign. Treatment of onco-associated venous thromboembolic complications is not an easy task, which is determined by the multiplicity of the pathogenetic mechanisms of hemostatic system disorders in the cohort of patients under consideration, who are threatened both in terms of the development of total PE and fatal bleeding. In addition to the features of the treatment phases, their duration, an important point in the treatment of cancer-associated thrombosis is a limited list of recommended drugs, as well as the permitted dosage regimens. The article analyzes the results of research aimed at studying the effectiveness of apixaban in the treatment of cancer-associated thromboembolic complications. Now the gold standard for the treatment of venous thromboembolic complications is dalteparin. However, low compliance in the use of dalteparin leads to premature termination of treatment or the patient's independent transition to alternative drugs. The appearance of direct oral anticoagulants has significantly changed the treatment paradigm in this morbid group of patients, while leaving a number of unresolved issues.

Atrial fibrillation (AF) is one of the most common types of cardiac arrhythmias, while AF is the main risk factor for ischemic stroke. For a long time, vitamin K antagonists, primarily warfarin, have been the standard for the prevention of thromboembolic complications in patients with AF. 5 years ago, dabigatran, rivaroxaban and apixaban occupied the 2nd place in the structure of anticoagulant prescribing (AC), giving way to warfarin. The well-known reason for the inadequate use of AC is the risk of bleeding. There are a large number of validated scales for assessing the risk of hemorrhagic complications, in particular HAS-BLED, ABC, HEMORRHR2HAGES, ATRIA, ORBIT, but the estimated high risk of bleeding should not be the only and absolute limitation to the appointment of AC. Despite the real risk of bleeding on the background of taking AC in patients with AF, an integrated approach taking into account not only the risk factors of the thromboembolic complications, but also hemorrhagic complications, with an emphasis on the existing comorbidities, the presence of comorbidity, old age, etc., will allow an individual approach to the choice of AC and its dose, contributing to the optimization of the management of such kind of patients.

The increase in the life expectancy of the population is accompanied by an increase in the prevalence of diseases for which old and senile age are risk factors. Atrial fibrillation (AF) and chronic kidney disease (CKD) are two diseases that can coexist in a patient. The risk of ac thromboembolic and hemorrhagic events in this case increases due to the mutual aggravating influence of these diseases. In addition, these patients have a high incidence of coronary events, and cardiovascular complications are the main cause of death in patients with AF and CKD. Consequently, such patients require an integrated approach to treatment, and their management is a complex clinical task. The direct oral anticoagulant rivaroxaban has been most studied in a population of comorbid AF and CKD patients and has proven a high efficacy and safety profile in these patients in randomized controlled trials. In addition, rivaroxaban has shown a significant reduction in the risk of myocardial infarction in various patients, as well as the possibility of preserving renal function to a greater extent compared with warfarin therapy, and a possible positive effect on reducing the risk of cognitive impairment. A single dosing regimen can improve adherence to treatment, which is one of the key conditions for achieving the above effects. Thus, these factors make it possible to achieve comprehensive protection of comorbid patients with AF and CKD.

Objective: To study the evolution of consumption of antithrombotic drugs used for the treatment of atrial fibrillation (AF) at the outpatient stage in the Saratov Region using the ATC/DDD (Anatomical Therapeutic Chemical Classification / Defined Daily Doses) and drug utilization 90% (DU90%) analysis.Material and methods. We analyzed the outpatient stage of treatment using the data reflected in 511 case histories of AF patients hospitalized in specialized cardiology departments of the Saratov Region in 2011–2018. The study of the consumption volumes of antithrombotic drugs was carried out using the ATC/DDD- and DU90%-analysis methodology. The consumption of drugs with proven efficacy in AF was expressed as the number of daily doses (NDDD) per 1000 AF patients per day.Results. In 2011, the number of prescribed DDD of oral anticoagulants (OACs) was 5.29 NDDD per 1000 AF patients per day, and all of them were represented by warfarin; in 2018, this indicator increased up to 277.51 NDDD per 1000 AF patients per day, of which direct OACs amounted to 237.06. The consumption of antiplatelet agents remained at a high level, and in 2018, was 582.53 NDDD per 1000 AF patients per day. Acetylsalicylic acid was included in the group of drugs accounting for 90% of all antithrombotic drugs at the outpatient stage – 99.02% in 2011, 93.08% in 2012, 58.55% in 2016, 60.27% in 2017, and 46.66% in 2018.Conclusion. The consumption volumes of OACs used at the outpatient stage of treatment of AF in the Saratov Region increased significantly in the period from 2011 to 2018, mainly due to direct OACs. At the same time, the consumption volumes of antiplatelet agents remained at a high level.

Aim. To evaluate the prevalence of oral anticoagulant therapy at the outpatient and inpatient stages in patients hospitalized with ischemic stroke.Material and methods. This open observational prospective real-world study included 114 patients with atrial fibrillation (AF) hospitalized with confirmed stroke.Results. Only 26,3% of patients with AF hospitalized with a confirmed diagnosis of ischemic stroke took anticoagulants (70% — direct oral anticoagulants (DOACs), 30% — warfarin). At the same time, among those taking warfarin, only one patient had normal international normalized ratio (INR) at the time of hospitalization (INR 2,6). In all other cases, the INR was

Study of synthetic and natural materials suitable for the creation of nanocarriers and their modification will provide a breakthrough in the treatment of many diseases. Glycosaminoglycans (heparin and its derivatives) are a good choice for creating nanocarriers due to their unique biological and physicochemical properties. The complexation of Pr (III), Sm (III), Eu (III) with heparin anions was studied by potentiometric titration at 37°C and an ionic strength of 0,15 M NaCl. Significant forms and chemical equilibria were determined using the NewDALSFEK program. In the pH range from 2,7 to 5, a complex of the type {[LnHep]}n is formed, where Hep3- is a monomeric unit of the heparin macromolecule. Data on the stability of nanocompositions were obtained: lgβ[PrHep]=4,27±0,04, lgβ[SmHep]=4,28±0,03, lgβ[EuHep]=4,28±0,03. The M06-HF method in combination with the CSDZ+* basic set was used to perform quantum chemical modeling of the complexes.

Background: Medication errors can cause preventable adverse events. For example, inappropriate use of anticoagulants (AC) can result in bleeding and thromboembolic complications. Detection and analysis of AC medication errors allow to reveal deficiencies in the safety systems in healthcare organizations., Aim: The study was aimed to develop a method of systematic detection of anticoagulant medication errors for consequent audit, analysis and development of medication safety improvement measures., Materials and Methods: The study was conducted in the multidisciplinary hospital and included 4924 patients admitted from January 2019 to December 2021 who received AC. Three laboratory triggers (international normalized ratio ≥4, serum creatinine ≥133 μmol/l, and glomerulofiltration rate <30 ml/min/1.73 m 2 ) helped to reveal 4304 cases. Their matching with patient's data helped to develop combined triggers. Two clinical pharmacologists reviewed all cases identified by combined triggers for checking medication errors. The trigger was considered positive when anticoagulant medication error was detected in the history selected by combined trigger., Results: Of the 4924 patients 253 (5.3%) were selected by combined triggers. Combined trigger allowed to reduce the amount of medical health records audit by 97.3%. Medication errors were detected in 137 patients. Positive predictive value of selected combined triggers varied from 0 to 63.9%. Aggregated positive predictive value of all combined triggers amounted to 54.2%. AC medication errors were detected in 2.8% patients., Conclusion: Method of systematic detection of AC medication errors using combined triggers in all hospitalized patients receiving AC allowed to reveal typical medication errors for consequent analysis and elaboration of measures to reduce preventable patient harm in healthcare settings.

The article is a non-systematic review of the literature, addressing the effectiveness, safety and appropriateness of antithrombotic drugs for COVID-19 in patients undergoing treatment in different settings: in the hospital phase, including the intensive care unit, in the outpatient phase after discharge from hospital, in primary outpatient treatment. The issues of thrombotic complications during vaccination and the necessity of their prevention are discussed. The studies confirm the importance of prophylactic doses of anticoagulants in all hospitalized patients. The use of increased doses has proven ineffective in patients with a severe course of the disease who are being treated in the intensive care unit. In moderately severe infections, there is a clear benefit of increased doses of anticoagulants in reducing the risk of organ failure, but definitive conclusions can only be drawn after the final results of the studies have been published. Prolonged pharmacological prophylaxis after hospital discharge may be useful in individual patients, but the overall risk of thrombotic complications in the long-term period does not appear to be high. The available data do not support the use of anticoagulants in the treatment of coronavirus disease in the outpatient settings, since the risk of thrombotic complications is not increased in such patients, and the safety of anticoagulant use has not been evaluated. Sulodexide may be useful in selected outpatients at increased risk of disease progression. Vaccination may provoke the development of atypical localized thrombosis by immune mechanisms, but the risk of such complications is lower in the coronavirus disease itself. Anticoagulant prophylaxis during vaccine administration is not indicated.

Aim. To study antithrombotic therapy (ATT) in patients with myocardial infarction (MI) type 1 and preexisting atrial fibrillation (AF), effect of ATT on prognosis. Material and methods. 100 patients with type 1 MI and preexisting AF were selected. The exclusion criterion was severe concomitant pathology. Results. Only 13.0% of AF patients took anticoagulants (AC) adequately before hospitalization. 94.0% of patients in hospital and 80.5% at discharge were prescribed triple ATT at least for 1 month with transition to dual ATT (AC + disaggregant) for 12 months. ACs were prescribed in hospital in 100.0% of cases, at discharge in 93.1%. After 1 year 8.4% of patients stopped taking ACs, after 2.31.9 years 15.7%. The incidence of ischemic and hemorrhagic events didnt differ in patients with different regimens of ATT (double/triple) and types of AСs (vitamin K antagonists/non-vitamin K antagonist ACs). In the long-term period patients, who took ACs incorrectly or stopped taking ACs, had increased risks of stroke (OR 9.580; 95% CI 1.15379.599, p=0.0365); combined endpoint: recurrent MI + stroke + cardiovascular mortality (OR 2.556; 95% CI 1.1045.918, p=0.0284). Сonclusion. Patients with preexisting AF had a low adherence to ACs prior to MI. It increased after hospitalization and decreased during follow-up. In the long-term period patients, who took ACs incorrectly or stopped taking ACs, had significantly increased risks of stroke, combined endpoint. There were no differences in the prognosis depending on the type of ACs, the regimens of ATT administered in accordance with ischemic and hemorrhagic risks.

Prevention of venous thromboembolic complications (pulmonary embolism, stroke, deep vein thrombosis) remains the most important clinical medicine problem and affects all doctors’ professional expertise areas without exeption due to an extremely high potential risk to the health and life of patients that might cause thromboembolic complications. A worldwide trend is to use conservative methods of treatment and prevention of pulmonary embolism, stroke, deep vein thrombosis, which are most often limited to the use of compression treatment, periodic appointment of phlebotropic medications courses. At the same time, effective and safe methods of using non-drug technologies for the prevention of thromboembolic complications in patients, in particular, with postphlebitic lower extremities syndrome, are in progress. They can prevent and/or significantly reduce the number of life-threatening complications and mortality with minimal risk of bleeding. The article presents a review of the literature data using the Russian and foreign sources on the use of medicinal and non-medicinal,mechanical methods of medical rehabilitation and sanatorium-resort treatment of patients with preventive effect on the dangerous thromboembolic complications occurrence.

During the pandemic of the new coronavirus infection, there is increasing evidence of neurological complications associated with COVID-19. There is no doubt that stroke can be a major complication in patients with severe disease course.Objective: to determine the safest and most effective anticoagulant for stroke prevention in patients with severe COVID-19.Patients and methods. A prospective study enrolled 520 patients with severe COVID-19. We used the following criteria for severe COVID-19: SpO2 30 breaths/min, lung infiltrates >50% on computed tomography. The study included 509 patients, divided into three groups depending on the type of anticoagulant therapy: patients of the 1st group received 24–36 thousand IU of heparin, patients of the 2nd group – enoxaparin at a dose of 1 mg/kg per day, patients of the 3rd group – rivaroxaban at a dose of 20 mg/day. The duration of anticoagulant administration depended on the severity of the patient's condition, dynamics of laboratory parameters (D-dimer, fibrinogen, international normalized ratio, activated partial thromboplastin time, platelet count), and varied from 2 to 6 weeks. In addition, we studied the incidence of ischemic and hemorrhagic strokes and transient ischemic attacks during a 6-week follow-up period. The article also presents a clinical case of large artery thrombosis in a young patient with severe COVID-19 without stroke risk factors.Results and discussion. Even against the background of active primary prevention, stroke incidence was 2.6% (0.6% for ischemic stroke, 1.4% for venous stroke, and 0.6% for hemorrhagic stroke). The highest stroke incidence was observed in the group of patients receiving heparin. In contrast, the prevention of thrombotic complications in patients receiving low-molecular-weight anticoagulants or rivaroxaban showed the best results with minimal morbidity and mortality in severe COVID-19.Conclusion. Stroke can be a complication of COVID-19, and preventive anticoagulant therapy using low-molecular-weight heparin or a factor X inhibitor effectively prevents this complication.

Aim. To study the structure of anticoagulant prescription in a general hospital to identify trends and contributing factors.Materials and methods. The study was conducted in an urban general hospital. According to retrospective retrieval from electronic health records, total 17,129 patients received anticoagulants from 2008 to 2018. Formal appropriateness of oral anticoagulants (OАС) prescriptions for 6,638 patients with atrial fibrillation (AF) was analyzed with CHA2-DS2-VASc score.Results. Appearance of recommendations for the direct oral anticoagulants (DOAC) prescription in clinical guidelines for venous thromboembolism (VTE) and AF management contributed to steady increase in the DOAC taking and decrease in the proportion of warfarin prescription. From 2011 to 2018, the proportion of patients with DOACs prescription increased from 1.7% to 81.5%. The most common indications for anticoagulant were ischemic stroke prevention in AF and VTE with mean rate 75.3% and 23.2%, respectively for the 2011-2018 period. Steady increase in low-molecular-weight heparin (LMWH) prophylactic prescriptions was also shown (Chi-square for linear trend=1340, df=1, p

The review presents modern data on the preventive effect of antiplatelet and anticoagulant therapy of placenta-associated diseases. The review includes data from foreign and Russian articles published over the past 15 years on the Scopus, Web of Science, MedLine, The Cochrane Library, EMBASE, Global Health, CyberLeninka, Pubmed databases. In recent years, there have been reports of the effectiveness of low molecular weight heparins in the prevention of placenta-associated complications. M. Rodger et al. In their study (2016), report on the effect of low molecular weight heparins on the development of placenta-associated complications. Patients whose previous pregnancy was complicated by preeclampsia or fetal growth restriction were randomized into 2 groups. The first group of pregnant women began to receive injections of low molecular weight heparins at an early stage of pregnancy (before 12 weeks), the second group did not receive low molecular weight heparins. Thus, only 19% of women receiving low molecular weight heparin therapy and 43% of women not receiving it developed placenta-associated complications, which may indicate the effectiveness of low molecular weight heparins. This data shows the urgency of the problem of placenta-associated complications, and the development of effective methods of early prevention of these diseases can improve the outcomes of the pregnancy.

The pandemic of the new coronavirus infection COVID-19 in 2020 has become the main health problem across the globe. A special characteristic of the SARSCoV-2 virus is tropism to the vascular endothelium with the development of endotheliitis, which entails a number of typical disorders of the blood coagulation system: coagulopathy with increased thrombin generation, D-dimer, decreased fibrinolysis and prolonged prothrombin time. The coagulation disorder in COVID-19 is called thromboinflammation. Hyperinflammation, increased blood levels of von Willebrand factor, coagulation factor VIII, neutrophil extracellular traps, platelet activation, microvesicles play a significant role in the pathogenesis of hypercoagulation in COVID-19. To date, it is known that cases of COVID-19 in children and adolescents constitute a small part of the total number of patients with diagnosed COVID-19, and disorders of the blood coagulation system are similar to those in adults. The degree of hypercoagulable syndrome and the risk of thrombosis depend on the severity of COVID-19. And for children they are most expressed with the development of a hyperinflammatory immune response, called multisystem inflammatory syndrome. At the same time, clinical studies of the pathogenesis of COVID-19 in adults and children and the search for optimal methods of therapy for thrombus inflammation, which underlies the pathogenesis of COVID-19, continue.

Our knowledge regarding chemical structure and properties of heparin and its derivatives, including biological properties in blood plasma, on the cell surface and while interacting with receptors, has been progressively growing. New insights are followed by the expansion of therapeutic opportunities and indications for the use of heparins. There are prerequisites for the creation of new generation drugs with modified properties that reduce a bleeding risk while applied for a non-anticoagulant goal. The non-anticoagulant heparin properties allow to consider it as a candidate for pathogenetic treatment of patients with COVID-19. This review focuses on the anticoagulant and non-anticoagulant heparin properties as well as the underlying molecular mechanisms.

Aim. To study the current state of the anticoagulant's prescription in elderly and senile patients with atrial fibrillation in the clinical practice of family medicine center, in the southern regions of the Kyrgyz Republic.Material and methods. Of the 1974 ambulatory medical observation cards, 470 patients with atrial fibrillation were selected who had indications for prescribing antithrombotic therapy (87 [18.5%] men and 383 [81.5%] women; 212 [45.1%] urban residents and 258 [54.9%] rural residents). The average age was 66.9±10.2 years. The analysis included data from 387 patients who received anticoagulant therapy. The frequency of prescribing antithrombotic therapy has been studied.Results. There were indications for anticoagulant therapy in 387 patients. Anticoagulants were taken by 167 (43.2%) patients, antiplatelet agents - 196 (50.6%), no therapy - 24 (6.2%). Anticoagulant therapy in 153 patients included warfarin, while only 11.8% had adequate INR control after one year of follow-up. Rivaroxaban was prescribed in 14 (8.4%) patients. 50% of patients had antiplatelet agents instead of anticoagulants, which were mainly prescribed by therapists of rural family medicine centers.Conclusion. In the southern regions of the republic, an unfavorable situation is observed with the prescription and management of elderly and senile patients on anticoagulant therapy. It is necessary to continue the research across the country in order to obtain a complete and real picture of the problem, and to develop a unified and relevant recommendation.

Atrial fibrillation (AF) is the most frequent type of supraventricular arrhythmias. The anticoagulant therapy should be prescribed to prevent thromboembolic events. According to randomized clinical trials, anticoagulants do not always prove their high efficiency in the real clinical practice. It is a complicated issue for any doctor to prescribe the anticoagulant therapy for patients with AF and CKD. 30 % of patients with atrial fibrillation are known to have chronic kidney disease, while 10-15% of patients with chronic kidney disease are diagnosed with atrial fibrillation. Currently, there are scarce studies into the use of direct oral anticoagulants in patients with atrial fibrillation and chronic kidney disease (in case of Glomerular Filtration Rate (GFR) below 45 ml/min/1.73 m2).Aim. To determine the dynamics of GFR in patients with AF and CKD (in case of GFR below 45 ml/min/1.73 m2).Material and Methods. The sub-analysis was carried out to examine a single-centre prospective study into the optimization of the anticoagulant therapy in the outpatient practice. Initially, 133 dabigatran taking patients were enrolled in the study, and 79 patients were included in the final analysis. Endpoints were changes in Glomerular Filtration Rate (CKD-EPI) formulae as of the inclusion date, in 6, 12, 24 and 60 months after the inclusion. Changes in the renal function shall mean a decrease or increase in GFR by ≥5 ml/min.Results. The average follow-up period for patients was 1785 ± 218 days. A GFR>45 ml/min/1.73 m2 occurred in 116 (87.2%) patients, and a GFR

Introduction. At present, hemostasis disorders still hold one of the lead places in the pathogenesis of reproductive losses associated with high risk of miscarriage and remain one of the major causes for developing serious obstetric complications. Relevance, efficacy and safety of using drugs containing acetylsalicylic acid (ASA) and low molecular weight heparins (LMWH) in pregnant women with thrombocytopenia comorbid with intravascular coagulation activation remain pressing issues. The study of thrombocytopenia pathogenesis during pregnancy and search for new methods of hemostasis correction are accounted for by high risk of developing diverse perinatal complications and necessity to conduct prophylactic measures for their prevention.Aim: to study hemostasis changes and clinical outcomes in pregnant women with thrombocytopenia, to substantiate the use of antiplatelet agents and anticoagulants in pregnant women with activated intravascular blood coagulation for preventing development of thromboembolic and placenta-associated complications of pregnancy.Materials and Methods. A multicenter prospective study was conducted by enrolling 299 pregnant women at a gestational age of22.85 [22.00; 25.00] weeks, whose average age was 31.06 [27.75; 35.00] years. There were distinguished three groups: main group (n = 124) consisted of pregnant women with lowered platelet count and activated intravascular blood coagulation, who received ASA preparations and LMWH in prophylactic doses for 4 weeks; pregnant comparison groups (n = 125) received no such drugs; control group (n = 50) consisted of women with normal platelet counts during physiological pregnancy. All patients underwent clinical, anamnestic and laboratory examination, and the clinical outcomes of pregnancy were assessed.Results. It was found that use of ASA (a combined drug: ASA 75 mg + magnesium hydroxide 15.2 mg/day) and LMWH (enoxaparin sodium) in pregnant women from the main group were noted to improve hemostasis parameters: via markedly increased platelet count, decreased fibrinogen level, prothrombin index as well as normalized antithrombin III level (p < 0.01). It was also found during treatment that the D-dimer level and the rate (83.6 ± 2.3 % and 72.4 ± 2.7 %) and the degree (86.4 ± 2.7 % and 74.4 ±2.8 %) of platelet aggregation in the main group (in contrast with comparison group) were significantly decreased (p < 0.01). The frequency of detected chronic placental insufficiency was significantly higher (p < 0.01) in the comparison group (n = 50; 41.32 %) vs. the main group after receiving ASA and LMWH (n = 20; 16.52 %). The incidence of moderate (p = 0.016) and severe (p = 0.018) preeclampsia was significantly higher in the comparison group vs. the main group. While comparing the volume of blood loss during delivery, there were no differences between the main group and the comparison group (p = 0.46); it was noted only a statistically significant difference compared to the control group (p = 0.04), in which the lowest blood loss was found (337.9 [200.0; 600.0] ml) in comparison with the other two groups (p1,3 = 0.05; p2,3 = 0.04). It should be noted that the volume of blood loss in all groups remained within the physiological permissible range.Conclusion. Our clinical and laboratory study allowed to substantiate relevance of using ASA and LMWH drugs in pregnant women with thrombocytopenia comorbid with confirmed activation of intravascular blood coagulation, for prevention of thromboembolic and placenta-associated complications of pregnancy as well as proved safety of such drugs during pregnancy.

Venous thromboembolism occurs in 48–200 out of 1,000 patients with brain cancer per year, which is significantly more frequent than in general population.Case report. A female patient had surgical treatment of anaplastic astrocytoma following radiotherapy and chemotherapy (temozolomide, irinotecan, bevacizumab) at the age of 17 years old. She also received dexamethasone. At the age of 20 years, she developed cancer recurrence, that required chemotherapy. After chemotherapy had been initiated, the patient developed deep vein thrombosis of the legs. Rivaroxaban 20 mg/d for 2.5 months with the subsequent switch to enoxaparin 60 mg/d showed no recanalization. Enoxaparin dose increasing up to 160 mg/d demonstrated incomplete recanalization, however, superficial venous thrombosis of the legs developed. Combination therapy with enoxaparin plus warfarin resulted in further deep and superficial veins recanalization.Discussion. In cancer-associated venous thromboembolism that is resistant to low molecular weight heparin monotherapy, short-term combination therapy with low molecular weight heparin and vitamin K antagonists can be considered. However, in recurrent cancer standard treatment protocols can be ineffective.

Thrombolytic therapy, which is a priority treatment strategy in patients with acute ischemic stroke in the first 3-4.5 hours after start of the disease, has significant limitations in case of background anticoagulant therapy. Mechanic thrombextraction is considered to be an alternative therapeutic strategy in case of inefficacy or contraindications to thrombolytic therapy. The article presents a clinical case of the 75-year old female patient with acute cardioembolic stroke on background of heart failure and atrial fibrillation. Long-term background usage of the direct oral anticoagulant due to atrial fibrillation is a limitation to use thrombolytic therapy, therefore mechanical thrombextraction was performed. The case presents possibilities of the successful interventional treatment of acute cardioembolic ischemic stroke. An example of a possible drug-drug interaction possibly leading to reduction of the effectiveness of anticoagulant therapy is shown.

We aimed to evaluate the treatment results in patients with internal carotid artery (ICA) and vertebral artery (VA) dissection. Materials and methods. We examined 285 patients (122 men and 163 women, mean age 37.7 8.1 years) with ICA dissection (n = 147), VA dissection (n = 122), or a combination of both (n = 16). The dissection presented as ischemic stroke in 175 patients and with local symptoms in the others. Out of 173 patients, 156 were managed conservatively. Efficacy of the conservative treatment in first 3 months was assessed in 143 patients who received anticoagulants (AC; n = 38), antiplatelets (AP; n = 42), both (n = 45) or no antithrombotic therapy (n = 18). Results. Good functional recovery (02 points on the modified Rankin Scale) after 3 months was noted in 70% of patients, with no statistically significant differences between the different treatment types. There were 3 (2%) deaths in patients with severe stroke receiving AC. Recurrent ischemic stroke occurred in 10% of patients most often (86%) occurring in the first 3 weeks and triggered by head movement, straining, or fluctuating blood pressure. No statistically significant differences were found between different conservative treatments. However, there was a tendency towards increased frequency of recurrent stroke in patients without antithrombotic therapy (22%), as compared with patients receiving AC (4%) or AP (12%). There were no strokes in 110 patients with local symptoms due to ICA/VA dissection during the observation period. Conclusion. There were no statistically significant differences in AC and AP efficacy in patients with ICA or VA dissection. A neck brace to prevent head movement and control of blood pressure are advisable alongside pharmacological therapy.

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Antiphospholipid syndrome is an acquired autoimmune thrombophilia characterized by the development of recurrent vascular thrombosis of any caliber and type or obstetric pathology and the mandatory identification of persistently positive antiphospholipid antibodies. The main drug in the treatment of patients with antiphospholipid syndrome is warfarin. The role of direct-acting oral anticoagulants in the treatment of antiphospholipid syndrome remains controversial. The article discusses modern data on the place of direct-acting oral anticoagulants in the treatment of antiphospholipid syndrome.

The coronavirus infection COVID-19 is a highly contagious disease caused by the SARS-CoV-2 virus. Specific prothrombotic changes of the hemostasis system in COVID-19 are associated with increased incidence of venous thromboembolic complications. The article is a literature review on the diagnosis, treatment and prevention of coagulopathy and venous thromboembolic complications associated with COVID-19. 11 studies evaluating the frequency of registration of venous thromboembolic complications and 11 clinical recommendations on correction of coagulopathy published before May 22, 2020 have been studied. The frequency of venous thromboembolic complications was unexpectedly high: 8–13% in the general ward and 9–18% in the intensive care unit against the background of preventive measures. Preventive doses of anticoagulants, low-molecular weight heparins or unfractionated heparin are indicated to all hospitalized patients. Prolonged prophylaxis after discharge from hospital can be recommended for those at high risk of venous thromboembolic complications and low risk of bleeding. An increase in D-dimer may be considered as an indication for instrumental detection of venous thromboembolic complications. If there is a suspicion of venous thromboembolic complications, anticoagulant therapy at therapeutic doses can be started before the diagnosis is confirmed: during inpatient treatment preference should be given to low-molecular heparin or unfractionated heparin, after discharge from hospital it is recommended to transfer to direct oral anticoagulants for a period of at least 3 months. Routine prevention of venous thromboembolic complications in ambulatory patients is not recommended.

Aim. Clinical characteristics of disseminated intravascular coagulation (DIC) in COVID-19 infection and assessment of the effectiveness of complex therapy for this syndrome at the stages of prevention and treatment of various complications. Materials and methods. The study of publications was carried out through search engines on the Internet using keywords. To diagnose the infection, the COVID-19 program was used on the MeDiCase platform, which is publicly available on www.medicase.pro, which suggests a diagnosis with a sensitivity of 89.47%. The study included 85 patients with acute COVID-19 with mild to moderate disease, aged 11 to 81 years. The presence of the pathogen was confirmed immunologically in 12% of patients; in other cases, the diagnosis was based on the results of an automated survey in the MeDiCase system. All patients, according to the MGNOT recommendations, were prescribed one of the oral direct anticoagulants - Eliquis at a dose of 5 mg 2 times a day, Ksarelto at a dose of 10 mg 2 times a day or Pradax at a dose of 110 mg 2 times a day for at least 2 weeks. All other drugs with antiviral, immunomodulatory effects, antibiotics were canceled. Results. The presence of DIC is substantiated by the morphological picture of changes in organs and tissues, clinical (hematoma-petechial type of bleeding in combination with thromboembolic syndrome and the presence of thrombovasculitis) and laboratory changes: an increase in the level of soluble fibrin-monomer complexes, D-dimer, hyperfibrinogenaemia, less often - thrombocytopenia, violation of fibrinolytic activity. The phenomenon of consumption of clotting factors and profuse bleeding are rare. Direct anticoagulants, fresh frozen plasma transfusions and plasmapheresis are used in the treatment of disseminated intravascular coagulation. The paper presents its own positive results of early prescription at the outpatient stage of direct oral anticoagulants in prophylactic doses (no case of disease progression), individual cases of the use of fresh frozen plasma and plasapheresis. Conclusion. DIC syndrome with the development of thrombovasculitis is the most important pathogenetic mechanism for the development of microthrombotic and hemorrhagic disorders in organs during infection with COVID-19, leading to dysfunction of the lungs, brain and other nerve tissues, kidneys, thromboembolic complications, etc. Many symptoms of the disease may be associated with a violation of the nervous regulation of the functions of organs and systems. Prevention of thrombovasculitis is effective already at the stage of the first manifestation of the disease with the outpatient use of direct anticoagulants (oral, low molecular weight heparins). In case of more severe manifestations (complications) of the disease, additional use of freshly frozen plasma and plasmapheresis is effective.