Introduction. For the prevention of recurrent ischemic stroke (IS) in patients with atrial fibrillation (AF), oral anticoagulants (OAC) are considered a priority. The comorbidity of AF patients raises a discussion about the non-alternative feasibility and exceptional clinical efficacy of OAC. The validity of the choice of a specific antithrombotic agent can be assessed using a dynamic assessment of the causes of the first and recurrent stroke in patients with AF.
Aim. To assess the frequency recurrent IS and quality of medicament prevention therapy in patients with AF depend on heterogeneity of stroke leading pathogenetic mechanism.
Materials and methods. The data from the register of 200 patients with IS and AF were analyzed. 55 (27.5%) patients suffered recurrent IS (24 (43,6%) men, 31 (56,4%) women, mean age 72,3 ± 10,2 years). The pathogenetic subtype of recurrent IS was determined, including a retrospective assessment of the pathogenetic subtype of a previous IS. We studied the presence and nature of antithrombotic therapy (ATT) preceding a second stroke.
Results. The first IS was due to cardiogenic embolism in 36.4% of patients, the atherothrombotic subtype occurred in 18.2%, and the lacunar subtype in 34.5% of patients. Embolic stroke from an undetermined source (ESUS) - in 10.9% of patients. OACs were prescribed only to 31.7% of patients, antiplatelet agents - to 14.6% of patients, 53.7% of patients did not receive ATT. The leading pathogenetic subtype of recurrent stroke was cardiogenic embolism (70.7%), the frequency of lacunar stroke decreased (4.9%), and the frequency of atherothrombotic stroke remained unchanged. In 14 patients with recurrent stroke, AF was first detected, including all patients with ESUS.

Conclusion. The proportion of recurrent stroke in patients with AF is 27.5%. Compared with the first stroke, recurrent stroke in patients with AF is characterized by an increase in the proportion of cardiogenic embolism up to 70.7%, which is due to the insufficient prescription of OAC, which must be recommended, including for patients with non-cardioembolic subtypes of stroke.

This review focuses on some aspects of anticoagulant therapy in the updated clinical guidelines for atrial fibrillation of the European society of cardiology, published in 2020. Atrial fibrillation is a polymorbid continuously developing syndrome, and therefore the treatment strategy is based on a comprehensive assessment of the patient, including the risk of stroke, the presence and severity of symptoms, and an assessment of structural heart disease and comorbidities. The review describes the principles of the proposed integrated approach, abbreviated “ABC pathway”, as reflecting the three main directions of the treatment strategy. According to experts, the clinical picture of AF (i.e. first detected, paroxysmal, persistent, long-term persistent or permanent) should not determine the indications for the appointment of anticoagulant therapy. The CHA2DS2-VASc scale continues to be the basis for stratification of thromboembolic risk. The role of dabigatran in primary and secondary prevention of stroke and systemic embolism in patients with atrial fibrillation is described. Changes in the position of experts regarding the assessment of bleeding risk are highlighted in order to help identify unmodified and eliminate modifiable risk factors for bleeding, as well as to identify AF patients who are potentially at high risk of bleeding for more frequent monitoring and monitoring of their condition. Questions about the use of direct oral anticoagulants in the choice of rhythm control tactics are highlighted separately. The use of dabigatran in patients undergoing cardioversion and catheter ablation is justified. Practical questions about the continuous strategy of anticoagulant therapy during ablation are highlighted separately. Changes related to multicomponent therapy after percutaneous coronary intervention are highlighted. The main measure to improve the safety of combined antithrombotic therapy is to minimize the duration of triple therapy. The updated recommendations supportlimiting the duration of triple antithrombotic therapy to 1 month, and also provide for early discontinuation of aspirin (≤1 week) and continuation of double antithrombotic therapy in cases of uncomplicated stenting and low risk of thrombosis, or when the risk of bleeding exceeds the risk of thrombotic events.

Edoxaban is a selective direct factor Xa inhibitor. Edoxaban in a dose of 60 mg per day is an effective and safe option in the prevention of thromboembolic complications in patients with nonvalvular atrial fibrillation, including in combination therapy in patients after percutaneous coronary interventions. ENGAGE AF-TIMI 48 is currently the most extensive study comparing direct oral anticoagulants and warfarin in patients with atrial fibrillation, both in terms of number of participants and duration of observation. For edoxaban, an adequate approach to dose reduction has been developed in patients with alikely increase in plasma concentration due to renal impairment, low body weight or inter-drug interactions. Such dose reduction does notlead to an increase in the frequency of ischemic complications.
Edoxaban is characterized by an optimal safety profile in patients with chronic moderate kidney disease, a small number of drug interactions and a convenient mode of administration. In patients with atrial fibrillation and concomitant ischemic heart disease, the use of Edoxaban is associated with a decrease in the frequency of myocardial infarctions, as well as strokes and episodes of systemic thromboembolism in comparison with warfarin. The drug can be successfully used as anticoagulant support for cardioversion and catheter ablation for atrial fibrillation.
Edoxaban intake does not require routinelaboratory control. In case of unexpected situations (life-threatening bleeding, urgent surgical intervention) in patients receiving edoxaban, to assess the degree of anticoagulation should use the determination of anti-Xa activity. Clinical studies of a specific antidote of edoxaban - andexanet alfa are ongoing. Before approval of the specific antidote in severe andlife-threatening bleedings against the background of edoxaban administration, the use of prothrombin complex concentrate should be considered. Data on the effective and safe use of edoxaban in routine clinical practice have been accumulated.

Introduction. Dyslipidemia and obesity are interdisciplinary and “multi-metabolic” diseases, pathogenetically associated with the development of atherothrombosis, which creates practical health problems. The development of both dyslipidemia and obesity is influenced by socio-demographic, environmental, genetic and many physiological and behavioral factors, while the contribution of genetic factors is 40-70%. The goal is to identify the genetic characteristics oflipid status and fat metabolism in the indigenous ethnic group of the Arctic region of the Russian Federation under conditions of permanent islandliving.
Methods. A cross-sectional population study of an indigenous ethnic group (n = 44) living on Vaygach Island (70 ° 01 ' Nlat 59 ° 33 ' E). The reported study was funded by RFBR according to the research project №18-00-00814-(18-00-00478). Serum cholesterol and triglycerides were determined as markers oflipid metabolism in blood serum. To analyze the genetic profile, the polymorphism of the FTO A23525T gene and the LPL Ser447Ter gene was determined by polymerase chain reaction.
Results. In the sample of the indigenous ethnic group, BMI was 26.0 [21.5; 29.75] kg/m². BMI for men is 23.0 [18.0; 28.0] kg/m², for women - 25.0 [18.0; 29.25] kg / m². Carriers of the unfavorable allele A had a higher BMI than carriers of the T allele. Analysis of the effect of rs9939609 genetic polymorphism on thelevel of total cholesterol did not show statistically significant differences between the FTO gene genotypes. A minimal triglyceride concentration was observed in carriers of the protective genotype Ter/Ter.
Conclusion. Understanding the similarities and differences in genetic susceptibility among different ethnic groups can ultimately contribute to a more focused primary prevention and patient-oriented approach of cardiovascular pathology.

The article presents an analytical review of the studies aimed at determining the optimal antithrombotic therapy in patients with atrial fibrillation undergoing elective or emergency percutaneous coronary intervention (PCI) due to the development of acute coronary syndrome (ACS). The results of the WOEST study are analysed. This study was the first to demonstrate an opportunity to safely discontinue administration of aspirin as part of the multicomponent antithrombotic therapy that included warfarin as an anticoagulant. Three studies were analysed - PIONEER AF-PCI, RE-DUAL-PCI and AUGUSTUS, where direct oral anticoagulants (DOACs) - rivaroxaban, dabigatran and apixaban were used as anticoagulants as part of the multicomponent therapy. The results of these studies formed the backbone of the updated European guidelines for the diagnosis and treatment of atrial fibrillation, 2020. The guidelines offer to divide patients with AF and ACS, who require multicomponent antithrombotic therapy, into two categories. The first group includes AF patients with uncomplicated PCI without a high risk of stent thrombosis, as well as patients with a risk of bleeding that prevails over the risk of stent thrombosis. The second category of patients, in contrast, is characterized by a high risk of stent thrombosis, which prevails over the risk of bleeding. In the absence of contraindications, the patients of both categories should choose DOAC as an anticoagulant and be prescribed clopidogrel as a P2Y₁₂ inhibitor for 12 months. In AF patients with uncomplicated PCI without a high risk of stent thrombosis, as well as in patients with a risk of bleeding, which prevails over the risk of stent thrombosis, the period of treatment with the second antiplatelet drug (aspirin) should belimited to the hospital stay. Patients at increased risk of stent thrombosis and reduced risk of bleeding can extend the aspirin therapy for 1 month. The approaches to the choice of the duration and composition of the multicomponent antithrombotic therapy in AF patients taking oral anticoagulants after elective PCI are similar to those in ACS patients, except for the duration of clopidogrel therapy, which is reduced to 6 months in all patients.

In case of early invasive approach to the treatment of acute coronary syndrome in patients without indications forlong-term anticoagulants, double antithrombocytic therapy is recommended - a combination of acetylsalicylic acid with one of the blockers of P2Y₁₂ platelet receptor (clopidogrel, prasugrel or ticagrelor). In this case, patients who do not have an excessively high risk of bleeding, there is evidence in favor of the choice of prasugrel or ticagrelor. Which of them is preferable in cases where in the first hours after hospitalization it is planned to perform coronary stenting is not fully clarified.
The drawbacks of the randomized open PRAGUE-18 study do not allow us to judge the comparative effectiveness and safety of prasugrel and ticagrelor in primary percutaneous coronary intervention.
ц The ISAR-REACT 5 study was relatively small and has its strengths as well as weaknesses. However, the European expert community considers the results to be sufficient to change the practical approaches to acute coronary syndrome treatment. Thus, according to the recommendations of the European Society of Cardiology for the treatment of acute coronary syndrome without stable ST segment elevations on ECG, which were updated in September 2020, prasugrel is proposed to be considered as a preferred treatment for ticagrelor in cases where the patient is directed to percutaneous coronary intervention (class IIa recommendation, degree of evidence B).

The review focuses on current guidelines for the use of medications that affect hemostasis in the treatment of patients with chronic ischemic heart disease (IHD). The review shows the important impact of negative outcomes of IHD on mortality from cardiovascular system diseases in the Russian Federation. The results of the most significant randomised clinical trials, which assessed the efficacy and safety of various antithrombotic therapy options in patients with various clinical manifestations of IHD, as well as methodological methods for individual assessment of ischemic and hemorrhagic risks, were discussed. Theoretically, the use of anticoagulants in combination with antithrombocytic drugs to reduce the risk of atherothrombotic complications in the phase of the stable course of the IHD is justified. The results of the COMPASS study, which proved the positive effect oflow-dose addition of rivaroxaban to acetylsalicylic acid on the risk of cardiovascular events, cardiovascular death and death from all causes in patients with chronic IHD with maintained sinus rhythm, are reviewed in detail. Discussions were held on how to determine the optimal duration of double antithrombocytic therapy in patients with IHD after percutaneous coronary intervention (PCI), taking into account individual values of ischemic and hemorrhagic risks. Long-term antithrombotic therapy schemes for patients with chronic IHD and atrial fibrillation (AF) that have not been exposed to PCI are presented, as well as current recommendations on how to choose the best antithrombotic therapy scheme for patients with IHD that have been exposed to PCI depending on the risk of stent thrombosis and the risk of bleeding. It has been substantiated that active differentiated antithrombotic therapy should be widely used in everyday practice, which, provided that ischemic and hemorrhagic risks are adequately assessed, creates a real prospect of reducing mortality from IHD and circulatory system diseases in general.

Introduction. The direct oral anticoagulants (DOC) therapy does not require alaboratory control; however, it may be required to determine the anticoagulationlevel to choose a treatment strategy if alarge bleeding is developing or emergency surgery is needed.
The objective of this experimental study was to investigate the relationship between the residual factor Xa (FXa) activity, anti-Xa activity units oflow molecular weight heparins (LMWH), and the apixaban and rivaroxaban plasma concentrations in a chromogenic anti-Xa assay.

Material and methods. Concentrated DOC solutions were prepared by extracting apixaban and rivaroxaban from crushed tablets using methanol and dimethyl sulfoxide, respectively. The resulting solutions were added to the donor plasma pool until final inhibitor concentrations are achieved in the range from 10 to 100 ng/ml plasma. Anti-Xa activity was determined using an STA-compact analyser and the Liquid anti-Xa reagent kit, an analysis protocol, and calibrators designed to control the LMWH therapy. The effect on the thrombin formation dynamics was investigated using the thrombin generation test (TGT) and the PPR reagent as a trigger (final concentrations of tissue factor are 5 pM, and those of phospholipids are 4 μM). TGT curves were analysed using the Thrombinoscope program.
Results. It was shown that in the anti-Xa activity test version designed to control the LMWH therapy, there is a high correlation (R2 > 0.98) between thelogarithm of the residual factor Xa activity and the content of apixaban and rivaroxaban in the range from 10 to 80 ng/ml. Rivaroxaban shows about 1.5 times more anti-Xa activity than apixaban at equal concentrations. It was also shown that apixaban and rivaroxaban at doses equal both in concentration and in anti-Xa activity differ in their effect on the thrombin formation dynamics and thrombin inactivation in the TGT.
Conclusion. In the LMWH anti-Xa activity test version, the measured range of apixaban and rivaroxaban includes 30 ng/ml and 50 ng/ ml concentrations taken as “cut-off points” to determine the treatment tactics in emergency cases. However, thelack of certified DOC calibratorslimits the use of this test in clinical practice.

Introduction. Thrombosis diagnosis and prevention in patients with Polycythemia vera (PV) suffered an ischemic stroke (IS) are still open. The aim was to find the reasons for systemic thrombogenicity and to compare the applicability of the main scales assessing thrombosis risk in patients with PV suffered IS.
Materials and methods. We followed up 127 people (42-75 y.o.), of which 68 were patients with PV suffered IS (group I) and 59 non-PV-patients with ischemic stroke (group II). Clinical study included common blood analysis, rheological properties of erythrocytes, coagulation and endothelial parameters, cytokines, inflammation markers, angiogenesis markers, and testing for the V617F mutation in the JAK2 gene. The follow up included common and neurological examinations as well, and the assesment of thrombosis risk factors with both Caprini scale and CHA2DS2-VASc scale. All patients were examined twice as in the acute period of IS as well as in 16-18 months.
Results. Between the groups no significant differences were found for the NIHSS average score and for Bartel index as well.The Caprini score belonged to the “very high risk” (score > 6) in both groups in the acute period of IS. At the same time, the score “8-10 points” prevailed in group II (68%) whereas the score “11-12 points” prevailed in group I.In the acute time of IS the CHA2DS2-VASc score revealed 12% of patients from both groups who had a score of “3-4 points” (moderate risk of thrombosis).In group I thrombotic complications rate correlated significantly with the JAK2V617F gene allelicloading (r = 0.236; p < 0.05), and the development of recurrence cerebrovascular disorders correlated significantly with Caprini score (r = 0.241; p < 0.05), but not with CHA2DS2-VASc score.Aiming to predict thrombotic complications in PV-patients the threshold (cut off) points were established for those markers as factor VIII, factor VII, red blood cell deformability, thrombin activated fibrinolysis inhibitor (TAFI), red blood cell count, white blood cell count, t-PA, VEGF-A, p-thrombomodulin, and ADAMTS-13.This pattern of parameters showed the odds ratio of thrombotic complications 10.3 (95% CI 7.6-13.8) in PV-patients in thelong-term period.At the end of the follow up the Caprini score showed a trend towards a decreasing in total while the CHA2DS2-VASc score remained virtually unchanged.
Conclusion. We assume the accurate assessment of thrombotic risk in patients with Polycythemia vera suffered an ischemic stroke requires a proposed pattern of parameters including the test for JAK2V617F allelicloading and the calculation of Caprini score but not CHA2DS2-VASc score. Final results may provoke to change standard antithrombotic therapy in those patients towards its intensification due to pathogenetic featues of cancer-associated thrombosis.

Aliterature review is dedicated to the use of Parnaparin in various surgical specialties. Prevention and treatment of thromboembolic complications is the major indication for the use of Parnaparin. In the review, the authors dwell on comparative studies of the efficacy oflow molecular weight heparins and unfractionated heparin. They also discuss in detail pharmacokinetics and pharmacodynamics of Parnaparin, its structure and effect on hemostasis components. Due tolack of direct comparative studies of variouslow molecular weight heparins, the authors provide reviews based on the network meta-analysis, which allowed them to identify the advantages of a specificlow molecular weight heparin by indirect comparison.
There are few direct comparative studies of variouslow molecular weight heparins in theliterature, which does not allow for an objective assessment of their advantages and disadvantages. The authors do not only provideliterature data on direct comparative studies, but also show data on indirect comparisons (network meta-analysis). They analysed the efficacy of Parnaparin and otherlow molecular weight heparins for the prevention of thromboembolic complications, treatment of deep vein thrombosis and post-thrombophlebitic syndrome. The issues of the efficacy of Parnaparin in chronic arterial insufficiency and use in acute coronary syndrome are highlighted separately. The final part of the review is concerned with a promising, butlittle-known area of prophylaxis of restenosis and prevention of atherosclerosis progression. Experimental studies have allowed us to state that Parnaparin is one of the most effectivelow molecular weight heparins as far as thromboembolic complications are concerned. Parnaparin significantly reduces frequency of DVT events and, at the same time, decreases major bleeding risk as compared with unfractionated heparin. No dose adjustment is required in obese patients. Dose adjustments are based not on body weight but on risk factors for thrombosis, and obesity is only one of them to be considered to choose a dose. Amonglow molecular weight heparins, Parnaparin is one of the most potent drugs that reduces the proliferative and migratory capacity of smooth muscle cells; however, further research is needed to assess the prospects of using Parnaparin for the prevention of restenosis.

Patients with CLI often present multilevel disease. They underwent multiply revascularization procedures aiming to save thelimb. The main obstacle is absence or poor outflow arteries. Inability to restore bloodflow usuallyleads to ischemia progression and consequent amputation. We describe two cases of successful treatment of patient with CLI after multiply ABF thrombosis and absence of outflow arteries.
The first 63 years old patient developed the third case of ABF thrombosis as a result of profunda and superficial femoral arteries chronic occlusion. We performed mechanical recanalization and angioplasty of anterior tibial, popliteal, subintimal recanalization and angioplasty of superficial femoral arteries. After that the ABFleg was sutured to subintimal space of femoral artery. The next case was another 63 years old patient with total chronic occlusion of iliac, femoral, popliteal and tibioperoneal trunk. We performed mechanical recanalization and angioplasty of anterior tibial, popliteal, subintimal recanalization and angioplasty of superficial femoral arteries. And then extra anatomy femoro-femoral autovenous bypass, distal anastomosis was performed by using subintimal artery space also. Thelong term period was 27 months for the first case and 20 months - for the second one. All bypasses were patient.
Therefore this described above approach of hybrid open and endovascular surgery could give additional chance forlowlimb revascularization in this so-called hopeless group with criticallimb ischemia.

Nonspecific aortoarteritis is a systemic disease, which has been referred to the group of vasculitis affecting elastic and muscular arteries oflarge and medium calibre with the inflammatory processlocalized in the media and adventitia. The article presents the history of development of ideas about clinical manifestations, morphological changes and the course of the disease from 1761 to the present day, the timeline of medical advances in this disease studies. The genuine interest in nonspecific aortoarteritis arose at the beginning of thelast century, when the Japanese ophthalmologist Mikito Takayasu reported unusual changes in the retinal vessels of a 21-year-old Japanese girl suffering from recurrent bouts of syncope. The first publications dealt with clinical manifestations in the patients, who had only brachiocephalic arterial involvement. In the early 60s, it was found that nonspecific aortoarteritis (Takayasu's disease) can affect not only the branches of the aortic arch, but also the thoracic aorta, renal and visceral arteries. It was the mosaic clinical manifestations in patients with various forms of Takayasu's disease that caused the presentation of the disease in theliterature until the mid-1970s under various terms such as “pulseless disease”, “arteritis of young women”, “brachiocephalic arteritis”, “atypical coarctation of aorta”, “Martorell's syndrome”, “syndrome of obliteration of the supra-aortic trunks”, “panaortitis” or “panarteritis”, “aortitis syndrome”, “mid-aortic syndrome”, “occlusive thromboarteriopathy”. The review details the epidemiology and prevalence of this disease. Views not only on the etiology and pathogenesis, but also on the methods of treating this disease have changed since M. Takayasu's publication in 1908. Much attention is paid to the historical aspect of the first surgical procedures. Starting in 1951, the surgical method has firmly taken the lead in the treatment of stenosis of the carotid arteries, thoracic aorta, renal and visceral arteries. Surgical concepts changed, but the literature data indicate the sustainability of the basic principle of treatment: combination of surgical interventions and various antiinflammatory therapy regimens.

Paradoxical thromboembolism due to the presence of an patent foramen ovale (PFO) is a rather rare phenomenon, especially when an embolism results in acute myocardial infarction (MI). The presented clinical case of the paradoxical embolism is interesting for several reasons: firstly, the patient's primary disease was deep vein thrombosis (DVT) and pulmonary artery thromboembolism (PATE); secondly, apparently, it was due to PATE and the subsequent overload of the right side of the heart that thelatent embolism became apparent; thirdly, the paradoxical embolism was apparently caused by the fragments of alarge thrombus stuck in PFO, fourthly, the current clinical situation was ambiguous with respect to medical decisions, primarily concerning antithrombotic therapy.