Antiplatelet agents are an integral part of the treatment of patients with various presentations of atherothrombosis. Among all drugs in this group, acetylsalicylic acid has the broadest evidence base. This review is devoted to the prescription of acetylsalicylic acid for the primary prevention of vascular complications in patients without clinically apparent atherosclerosis. Current approaches to the risk stratification of ischemic events and determination of indications for such treatment are discussed. Primary prevention trials have been focused on the risk assessment scales, the prognostic value of which raises many questions. In this context, besides the traditional (classical) factors underlying these scales, it is reasonable to take into account the so-called “risk modifiers” that can affect the likelihood of CVC. The coronary artery calcium score is one of the strongest risk modifiers. The characteristics of key primary prevention trials, which included patients of different ages with various risk factors, are provided. In accordance with the current guidelines of European and Russian expert communities, the acetylsalicylic acid may be prescribed to individuals with a high risk of vascular complications, among which the best evidence base is available for patients with diabetes mellitus. The positive effects of antiplatelet treatment have been demonstrated to be maintained in the settings of modern therapy with a proven positive effect on the prognosis. A particular focus has been placed on minimizing bleeding. The correct assessment and correction of modifiable hemorrhagic risk factors, the use of drugs to protect the stomach, and the appointment of acetylsalicylic acid in the minimum effective dosage of 75 mg per day are called upon to increase the safety of treatment. A preference in favour of uncoated forms that are absorbed in the stomach for obese and diabetic patients may be discussed.

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.

After the appearance of direct oral anticoagulants (DOAC), the use of vitamin K antagonists (VKA) has become more rare, but nevertheless, there are diseases in which they remain indispensable drugs. This review is devoted to VKA and the diseases in which these drugs can be used. The article compares the mechanism of action of VKA and DOAC, discusses methods of monitoring VKA therapy. Among the diseases of non-alternative use of VKA, mechanical prosthetic heart valves, atrial fibrillation in patients with moderate and severe mitral stenosis, antiphospholipid syndrome should be mentioned. Another indication for the appointment of anticoagulants is thrombosis of the left ventricle. In patients who have survived a myocardial infarction complicated by left ventricular thrombosis, anticoagulant treatment should be continued for up to 6 months with repeated imaging control. For this purpose, warfarin is successfully used. Currently, there is insufficient data to recommend the routine use of DOAC in patients with KrCl less than 25–30 ml/min, and in routine practice, warfarin remains the main anticoagulant in such patients. Direct oral anticoagulants have practically not been studied in the so-called special groups of patients: patients with congenital thrombophilia and rare localizations of thrombosis. There were practically no such patients in randomized trials and very little is known about the effectiveness of DOAC, so today warfarin remains the main drug for their treatment. Despite the fact that DOAC has displaced VKA in patients with non-valvular AF, we should not forget that it is VKA that we are obliged to prove the effectiveness of anticoagulants in patients with AF. The article discusses the pharmacogenetics of warfarin in relation to the data of the Russian Federation, as well as the practically important question of the possibility of resuming anticoagulants in patients with bleeding, the results of their own research are presented.

Cancer is one of the most significant risk factors for venous thromboembolic complications (VTEC), which combines deep vein thrombosis and pulmonary embolism. Of the many well-known risk factors for VTEC, only cancer is associated with a 4-fold increased risk of venous thrombosis, and in cancer patients receiving chemotherapy the risk increases by up to 6.5-fold. Venous thrombosis is increasingly common in cancer patients and contributes significantly to the course of the underlying disease and mortality, especially when combined with additional risk factors, the most significant of which are surgery and chemotherapy treatment. The prevention and treatment of VTEC in cancer patients is a challenge, primarily due to the pathogenesis of cancer-associated thrombosis, the presence of additional risk factors associated with cancer, the high risk of haemorrhagic complications, reduced renal function and the recurrent nature of VTEC. Aspects of safe prevention remain an integral part of the management of patients with active cancer. The most vulnerable periods for the development of VTEC are the periods when the patient is hospitalised for surgical or therapeutic treatment and the long period of chemotherapy treatment on an outpatient basis. A comprehensive approach to the prevention of VTEC in patients with cancer should primarily involve careful selection of high-risk patients at each stage of treatment of the malignancy; these patients are the ones who will benefit most from drug thromboprophylaxis. The treatment of an already confirmed VTEC in a cancer patient always involves the additional challenges of drug interactions and increased haemorrhagic risk due to prolonged use of treatment doses of anticoagulants, which may in turn affect the effectiveness of chemotherapy or the efficiency and safety of anticoagulant therapy.

Introduction. Thrombotic complications (TC) in different vascular systems dictate the fate of high-risk patients. In cardiological practice, patients with advanced atherosclerotic vascular disease (MFA) represent the most vulnerable group. Malignant neoplasm (MN) is one of the most significant risk factors for developing TCs, especially in the context of antineoplastic therapy. The presence of significant differences in the mechanisms of thrombogenesis in malignant neoplasms and atherosclerosis determines the appropriateness of a comparative study of markers of coagulation activation and endothelial damage in order to identify common features and differences specific to each pathology.

 Aim. To examine markers of coagulation activation and growth factors in active cancer and advanced atherosclerotic vascular disease, to identify their common features and differences specific to each pathology.  

Materials and methods. A total of 22 patients with MN (Group 1) and 58 patients with MFA (Group 2) were enrolled in the study. The assessed biomarkers included: von Willebrand factor (VWF), D-dimer, growth differentiation factor-15 (GDF-15) and vascular endothelial growth factor A (VEGF-A).  

Results. Patients with MN had an increased likelihood of disease progression within 6 months at D-dimer level > 1121 ng/mL (OR = 10.5; 95% CI 1.4–81.0, p = 0.014) or VWF > 189% (OR 10.5, 95% CI 1.36–81.0, p = 0.014); the likelihood of death within two years of follow-up at D-dimer level > 1121 ng/mL (OR = 7.0; 95% CI 0.97–50.57, p = 0.04), or VWF > 203% (OR = 10, 5, 95% CI 1.36–81.06, p = 0.014). In patients with MFA, the likelihood of prognosis determining events within one-year of follow-up was determined by increased levels of VWF > 157% (OR = 9.2, 95% CI 1.02–82.8, p = 0.048) and GDF-15 > 1548 pg/ml (OR = 5.7; 95% CI 1.09–29.5, p = 0.04).  

Conclusions. Endothelial damage and coagulation activation are more pronounced in patients with MN than in patients with MFA. In patients with malignant neoplasms, the outcomes were associated with D-dimer and VWF levels, and in patients with MFA – with VWF and GDF-15 levels.

Von Willebrand factor (VWF) is a multimeric plasma glycoprotein present in endothelial cells, megakaryocytes, platelets, and connective tissue. It mediates platelet adhesion in small arteries. VWF also binds and protects coagulation factor VIII from degradation. Moreover, VWF is involved in inflammatory response, linking hemostasis and inflammation. VWF multimers and platelets attached to damaged or activated endothelium mediate leukocyte recruitment, facilitating local inflammatory response. At shear rates above 5000 s^–1, VWF molecules are capable of hydrodynamic activation that changes their conformation from globular to fibrillar. Therefore, VWF plays a key role in cellular hemostasis at high shear rates. Acquired and inherited disfunction, defective synthesis or increased proteolysis of VWF multimers lead to bleeding, as in von Willebrand disease or Heyde syndrome. Pathological activation of VWF may lead to the development of thrombotic complications of coronary artery disease. COVID-19, especially severe form, is characterized by prothrombotic shift in pulmonary vascular bed. Following endothelial damage, VWF plasma level rises and ADAMTS-13 activity decreases. In patients with COVID-19, a change in the VWF/ADAMTS-13 ratio is associated with an increase in the risk of thromboembolic complications. Therefore, assessment of hydrodynamic activation of VWF under flow conditions may be valuable in fundamental research and laboratory diagnostics.

Thromboembolic syndrome, the frequency of which is 8–15%, is the main danger for a patient with atrial fibrillation (AF). The left atrial appendage is the most common source of thromboembolia in atrial fibrillation. The frequency of detection of left atrial appendage thrombus in AF is 15.2% in the absence of anticoagulant therapy and 1–8% in patients using this group of drugs. The reason for the formation of thrombi in this localization during anticoagulant therapy today it is not reliably known. This article describes a clinical case of a 67-year-old patient with persistent AF and left atrial appendage thrombosis, who was hospitalized to determine further management strategies. A left atrial appendage thrombus lasted for a year despite continuous anticoagulant therapy with various oral anticoagulants at doses consistent with clinical guidelines due to the patient's absolute refusal to take warfarin, vitamin K antagonist. In addition, this article discusses the use of Thrombodynamics, a new global coagulation test, in patients with AF, which revealed a plasma hypercoagulable state with underlying persistent thrombosis in this patient on continuous oral anticoagulant treatment. The Thrombodynamics test is a promising procedure for assessing the coagulation system state and may be promising as a method for measuring the effectiveness of any oral anticoagulant. However, it is impossible to draw any definite conclusions on the basis of single observations; large clinical studies with the potential of long-term case follow-up of patients are needed.