The article is devoted to modern approaches to the selection of optimal dosage forms of acetylsalicylic acid (ASA), which ensure high bioavailability of ASA drugs. The relevance of improving the tactics of ASA use for both primary and secondary prevention of cardiovascular diseases is discussed. Changes in the role of ASA in the prevention of cardiovascular disease complications are discussed, including as part of combined antithrombotic therapy, including ASA and either P2Y12 inhibitor or low-dose rivaroxaban. Evidence is presented that has led to doubts about the sufficient bioavailability of the enteric form of ASA, as well as the predictability of the response to therapy. A separate part of the article is devoted to the safety of different forms of ASA, in particular - the effect on the mucosa of the small intestine. The results of clinical studies evaluating the effect of ASA intake in enteric-soluble and buffered forms on the small intestinal mucosa and the risk of bleeding are presented. In addition, the problem of decreased effectiveness of ASA intake in overweight or obese individuals is considered. The article provides information on ongoing randomized trials to assess the effectiveness of increasing the frequency of ASA intake, as well as the effectiveness of chronopharmacological approaches to optimize the use of ASA. The analysis performed leads it to conclude that the buffer form can now be considered the preferred acetylsalicylic acid (ASA) dosage form, which, on the one hand, exerts a less pronounced effect on the gastric and small intestinal mucosa, and on the other hand, ensures high bioavailability, as well as minimal variability of treatment response.

Currently, direct oral anticoagulants (DOACs) should be preferred when prescribing anticoagulant therapy to atrial fibrillation patients because of their lower potential for interactions and risk of bleeding than warfarin. However, in the absence of standardized laboratory tests and a specific antidote (except dabigatran), prescribing and monitoring DOAC therapy remains a challenge for clinicians and patients. The present review focuses on the problems of DOAC laboratory evaluation, indications, and prospects for its use. Routine coagulation tests including activated partial thromboplastin time, prothrombin time and thrombin time are not recommended for DOAC therapy. Currently, there are specific coagulation tests (anti-Xa activity factor determination for apixaban/ rivaroxaban and diluted thrombin time for dabigatran) that allow judging the presence of the drug in the blood. According to current recommendations, these tests should be used only to assess anticoagulant concentrations and not to adjust doses and decide on the timing of withdrawal before invasive intervention. Nevertheless, the issue of determining DOAC concentration during invasive interventions, the need for which only increases with age, is most relevant. Also a possible additional factor that may alter the bioavailability and pharmacokinetics of DOAC and be taken into account in the evaluation of laboratory activity is the presence of chronic renal disease, hepatic insufficiency, low or excess body weight. The use of specific coagulation tests for patients undergoing elective and urgent surgery among special categories of patients (with chronic kidney disease, low or excess body weight, renal failure) is promising.

Clopidogrel is the most studied P2Y12 receptor blocker and still has no alternative in a number of categories of ACS patients in whom ticagrelor or prasugrel have not been studied or their use is associated with an unacceptably high risk of bleeding. The review is devoted to a detailed consideration of these clinical situations, both in the light of the evidence base for the benefits of clopidogrel andthe practical aspects of its use. Clopidogrel remains the drug of choice in ST-segment elevation ACS patients undergoing thrombolysis, pharmacoinvasive strategy is implemented, and reperfusion therapy is not used at all. In patients with ACS without ST-segment elevation, clopidogrel is preferable in high risk of bleeding. The article discusses in more detail some particular cases of high bleeding risk in ACS patients, in which it is advisable to use clopidogrel: concomitant use of oral anticoagulants, active cancer, chronic kidney disease stages IV-V. Relatively new data on the peculiarities of ACS antiplatelet therapy in the mongoloid race are discussed, which is relevantto the Russian Federation. In real clinical practice, clopidogrel is often used because of intolerance, contraindications or unavailability of more powerful P2Y12 receptor blockers. Affordability, good tolerability, greater safety (including in relation to the development of recurrent minor “annoying” bleedings), single dose clopidogrel and availability of fixed combinations with acetylsalicylic acid result in better adherence to treatment with this drug than with more powerful P2Y12 receptor blockers, which in real-world settings may provide a more optimal treatment outcome. The article discusses approaches to forced de-escalation of antiplatelet therapy – switching from a more potent P2Y12 receptor blocker to clopidogrel. Data is also presented on the study of routine de-escalation at the end of the acute ACS period, both empirical and controlled by functional or genetic tests characterizing the efficacy of clopidogrel. Although routine de-escalation is not currently recommended, randomized trials suggest that this treatment strategy is promising for preventing hemorrhagic complications and reducing the cost of managing patients with ACS.

Parenteral administration of high (therapeutic) doses of anticoagulants is a mandatory component of the initial treatment of acute coronary syndrome (ACS) unless contraindicated. In ACS, intravenous administration of unfractionated heparin, the use of low molecular weight heparin enoxaparin, selective antagonist of activated X clotting factor fondaparinux sodium and direct thrombin antagonist bivalirudin are possible. The review presents current approaches to the choice of drugs and the specifics of parenteral anticoagulant use depending on ACS variant (with or without persistent ST-segment elevations on ECG), approaches to myocardial revascularization, previous use of oral anticoagulants, renal function, risk of major bleeding, presented in current versions of European Society of Cardiology and Russian Society of Cardiology guidelines, approved by the Russian Ministry of Health. It is shown that, according to the results of randomized controlled trials and expert opinion, for most ACS treatment scenarios (streptokinase thrombolytic therapy or no reperfusion therapy in ACS with persistent ST elevation on ECG, ACS without persistent ST elevation) the optimal approach is parenteral administration of sodium fondaparinux. Exceptions include primary percutaneous coronary intervention and very early invasive treatment of ACS without persistent ST-segment elevation, but initial treatment with sodium fondaparinux does not prevent these approaches. Additional advantages of sodium fondaparinux are the absence of the need to monitor the coagulation system, a fixed dose, as well as the possibility of use in patients with significant thrombocytopenia. If short-term use of parenteral anticoagulant is expected (in early invasive treatment of ACS), there are contraindications or limitations to the use of sodium fondaparinux and sodium enoxaparin, the means of choice for most cases is intravenous administration of unfractionated heparin.

The paper presents the experience of treating a patient with acute coronary syndrome without ST segment elevation and underlying severe novel coronavirus infection (COVID-19) complicated by polysegmental viral pneumonia and significant respiratory events. Emphasis has been placed on the use of antithrombotic therapy after endovascular treatment. A 56-year-old patient underwent respiratory support (non-invasive face mask lung ventilation followed by high-flow oxygenation), urgent diagnostic coronary angiography followed by percutaneous coronary intervention (balloon angioplasty and stenting of the right coronary artery and anterior interventricular artery). In addition to the etiopathogenetic therapy for coronavirus infection, the patient received combination antithrombotic therapy, including acetylsalicylic acid, prasugrel, FRaMon monoclonal antibodies (single exposure, intraoperatively), sodium enoxaparin. The therapy resulted in normalization of hemodynamic parameters, stable normothermia, absence of catarrhal events, improvement of exercise tolerance. A chest ultrasound imaging showed consolidation events, inflammatory markers significantly decreased, circulatory deficiency events were compensated, anginal pains did not recur. On the 20th day of hospitalization, the patient was discharged home with outpatient follow-up. The use of potent antiplatelet agents such as prasugrel or ticagrelor combined with IIb/IIIa receptor inhibitors and prolonged anticoagulant therapy can potentially improve the outcome of the disease in acute coronary syndrome with underlying severe coronavirus infection. In the presented clinical example, the use of aggressive approaches to the antithrombotic therapy did not lead to the development of significant hemorrhagic or other complications.

Introduction. Ischemic heart disease is undoubtedly the main factor that significantly aggravates the condition of patients with chronic lower limb ischemia in the perioperative period.

Aim. To establish the expediency of mandatory performance of selective polypositional coronary angiography in patients with chronic ischemia of the lower extremities to determine the stages of surgical intervention and prevent cardiac complications.

Materials and methods. The study included 285 patients, treated to the Department of arterial pathology surgery of the Bakulev National Medical Research Center of Cardiovascular Surgery with a diagnosis of chronic lower limb ischemia. The patients were divided into 2 groups. The main group included 139 patients admitted in 2016. The control group – 146 patients admitted in 1989. In the main group, all patients underwent coronary angiography. In the control group, coronary angiography was performed only in patients with a clinical picture of coronary artery disease or in asymptomatic patients after positive stress tests.

Results and discussion. After analysis of coronary angiograms in patients of the main group, out of 139 patients included in the study, 124 (89.2%) had a lesion of at least 1 coronary artery >50%; and in 101 (72.7%) patients, at least 1 coronary artery was affected >70%. In the main group, cardiac complications were noted in 6 (4.32%) patients, while in the control group they were detected in 21 (14.4%) cases. These complications appeared due to the underestimation of the state of the coronary bed, based only on the results of stress tests.

Conclusions. Selective polypositional coronary angiography is the main method for detecting asymptomatic significant coronary artery disease in patients with CLCI, which improves the immediate results of surgical treatment by reducing the incidence of cardiac complications.

The COVID-19 epidemic is accompanied by an increase in the frequency of rhythm disturbances and, in particular, atrial fibrillation. This article is a clinical analysis of a patient whose atrial fibrillation (fluttering) occurred due to an infection. Using the example of patient management, the issues of anticoagulant support for catheter ablation are considered, the algorithm of perioperative management of patients constantly receiving direct oral anticoagulants (DOAC), adopted in the National Medical Research Centre of Cardiology, is given. The reasons for omitting dabigatran before surgery in a patient are discussed, taking into account the dose of injected unfractionated heparin during catheter ablation. The analysis examines the role of COVID-19 in the origin of atrial fibrillation, provides medical literature data on the incidence of atrial fibrillation during the pandemic. It is indicated that the pandemic is accompanied by an increase in the frequency of atrial fibrillation and an increase in the frequency of stroke and death associated with this rhythm disorder. The question of the optimal choice of anticoagulant in a patient with atrial fibrillation that occurred during COVID-19, taking into account the pharmacological properties of DOAC, is considered. It seems that dabigatran has a minimal risk of drug interactions with drugs for the treatment of COVID-19, which are metabolized by cytochrome P-450 and are substrates for P-glycoprotein. In addition, dabigatran has minimal hepatotoxicity among DOAC registered in the Russian Federation. Much attention in case report is paid to the need for the appointment of DOAC after the procedure of catheter ablation in case of restoration of the sinus rhythm. It is emphasized that modern guidelines for managing the risk of stroke during catheter ablation emphasize the need to take anticoagulants for two months. The need for prolonged use of anticoagulants in case of preservation of the sinus rhythm is determined only by the risk of stroke/thromboembolism that the patient has.

The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) stimulated the development of highly effective vaccines that were produced with unprecedented speed with the use of new technologies. All the newly developed vaccines are highly effective with minimal adverse effects. Clinical introduction of the AstraZeneca Covid-19 vaccine has raised public alarm regarding the rare, but serious thrombotic events, known as vaccine-induced immune thrombotic thrombocytopenia (VITT). VITT is characterized clinical and laboratory syndromes like: venous (acute cerebral sinus venous thrombosis and abdominal vein thrombosis) or arterial thrombosis; mild-to-severe thrombocytopenia; positive antiplatelet factor 4 (PF4)-polyanion antibodies or anti-PF4–heparin antibodies detected by ELISA; occurring 5–30 days after ChAdOx1 nCoV-19 (AstraZeneca) or Ad26. COV2.S (Johnson & Johnson/Janssen) vaccination and elevated D-dimer. From a pathophysiological point of view, VITT is an autoimmune disease characterized by the development of antibodies that directly activate platelets, causing thrombosis in the arterial or venous systems of the body. At the same time, the components of the vaccine serve as an antigen for the formation of autoantibodies, which enhance the production of platelet factor PF4, which contributes to the formation of blood clots. It has established that intravenous use of immunoglobulin at a dose of 1 g/kg of the patient’s body weight per day, in addition to neutralizing antibodies, makes it possible to suppress VITT-mediated platelet activation. Fondaparinux, direct oral anticoagulants (DOACs), danaparoid or argatroban are the main anticoagulant drugs effective in the treatment of thrombotic conditions in VITT.

Introduction. Increased expression of tissue factor by tumor cells, formation of procoagulant microparticles and secretion of proinflammatory cytokines that activate leukocytes and endothelial cells are considered to be the main factors provoking blood coagulation activation in cancer patients.

The aim of the investigation was to study the peculiarities of hemostasis activation markers and endothelial damage in patients with active cancer.

Materials and methods. Patients with active cancer were included in the study. We determined the following biomarkers: fibrinogen (Fg), von Willebrand factor (vWF), D-dimer (D-d), growth differentiation factor 15 (GDF-15), vascular endothelial growth factor A (VEGF-A).

Results. Twenty-two patients with active cancer were included in the study. The median follow-up of the patients was 180 days (minimum 90, maximum 240). The presence of metastatic lesion was found in 62% of patients. At the end of the follow-up period (after 6 months) remission of the underlying disease was observed in 45.5% of patients, and 54.5% of patients were found to have progressed oncoprocess. GDF-15 levels ranged from 1486 to 11,722 pg/ml and were above normal values in all patients. Significant variability was also revealed in the level of VEGF-A - from 1 to 2944 pkg/ml, and only in 7 (32%) patients its level corresponded to normal values (0-66 pkg/ml). High levels of Fg (>3.6 g/L), D-d (>500 ng/ml), and vWF (>160%) were detected in 19 (86%), 18 (82%), and 17 (77%) patients, respectively.

Conclusions. The pilot study demonstrates a pronounced activation of the blood coagulation system and endothelial damage in patients with active cancer receiving chemotherapy and having a high risk of venous thromboembolic complications. The detected relationship of markers characterizing blood coagulation activation (D-d) and endothelial damage (vWF) with the progression of oncoprocess necessitates their further study in this category of patients.

Plasma fibronectin is a high molecular weight adhesive glycoprotein. There are two types of fibronectin: plasma (soluble) and cellular derived (insoluble). Electron microscopy revealed two types of structural organization of fibronectin: compact and expanded. In solution, fibronectin has a compact conformation, and after binding to certain substrates (collagen, fibrin, heparin), it is expanded. Plasma fibronectin is one of the main opsonins of blood plasma in relation to the “targets” of phagocytosis of a predominantly non-bacterial nature, as well as to some types of bacteria. For the treatment of septic processes, as well as respiratory distress syndrome of adults with severe fibronectin deficiency, plasma cryoprecipitate is used – a donor plasma preparation containing a large amount of plasma fibronectin (more than 2 mg/ml). It was proposed to replenish the level of fibronectin in patients with sepsis and other conditions that cause plasma fibronectin deficiency with the help of donor freshly frozen plasma. Transfusion of large volumes of freshly frozen plasma (up to 1000–1500 ml) to patients effectively eliminates the deficiency of plasma fibronectin. The concentration of plasma fibronectin in the blood significantly decreases after the addition of severe infectious processes to hematological diseases, as well as acute DIC syndrome. Extracorporeal methods of blood purification – selective plasmapheresis – have been developed to correct immunocomplex and fibronectin-complex pathology. Two variants of selective plasmapheresis have been proposed: the method of heparinocryoprecipitation of plasma proteins and the method of heparinocryofractionation. In 1987, a plasma heparin precipitate was proposed as a source of fibronectin for the treatment of patients with trophic skin lesions. In 1992, a new method was proposed for obtaining blood preparations with a high concentration of plasma fibronectin from patients themselves (heparin cryofractionation). Autofibronectin preparations obtained by such methods are effective in the local treatment of trophic ulcers in 90–93% of cases. The proposed drugs are safe against infection of patients with infectious diseases transmitted through the blood.