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Aterotromboz = Atherothrombosis

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No 2 (2021)
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https://doi.org/10.21518/2307-1109-2021-2

ANTITHROMBOTIC THERAPY

6-17 1241
Abstract

The article presents an overview of publications describing the mechanisms of the development of the pathological process in patients infected with SARS-CoV-2 coronavirus. The authors analysed publications showing that damage to the endothelium and endothelial glycocalyx is the main factor influencing the development of coronavirus COVID-19 infection. It is the endothelium inflammation caused by a virus that leads to the dysfunction of the vascular system and the development of coagulopathy. Using scanning electron microscopy and flow cytofluorimetry, we showed that patients with COVID-19 of moderate severity (CT2) had significant desquamation of endothelial cells (concentration of circulating endothelial cells (CEC) in blood is 300-400 cells/ml whereas the normal range is no more than 10 cells/ ml). Such desquamation should cause exposure of the pro-inflammatory and thrombogenic subendothelial matrix, which, as a results, leads to the development of thrombotic disorders of the circulatory system. Therefore, it is only natural to try to counteract disease progression by protecting the endothelial glycocalyx from damage. Sulodexide, a mixture of fast-moving heparin fraction (80%) and the glycocalyx element dermatan sulfate (20%) obtained from the mucous membrane of the small intestine of pigs, is very promising in this regard. This drug can significantly reduce the inflammatory process, protect the glycocalyx and endothelium from damage, resulting in lowering the degree of thrombus formation in patients with coronavirus COVID-19 infection, which relieves the course of the disease and improves its outcome. The experimental data presented in the review, although obtained in not large enough population of patients, allow us to consider sulodexide a promising drug that protects the endothelium and suppresses thrombosis in COVID-19.

18-28 640
Abstract

The article discusses data on the duration of risk retention and the main cause of vascular complications in patients with acute coronary syndrome. Preconditions for prolonged use of dual antiplatelet therapy after myocardial infarction are presented. The authors consider the results of a large, prospective, randomized, placebo-controlled, multinational PEGASUS-TIMI 54 study evaluating the efficacy and safety of the long-term use of acetylsalicylic acid combined with ticagrelor (P2Y12 platelet receptor blocker) in patients with a high risk of thrombotic complications of atherosclerosis in the period from 1 to 3 years after myocardial infarction. The article presents an analysis of optimal approaches to prolonged double antiplatelet therapy after myocardial infarction, taking into account the results of the PEGASUS-TIMI 54 study, which laid the foundation for current clinical guidelines. The PEGASUS-TIMI 54 study demonstrated the benefits of prolonged dual antiplatelet therapy for at least 4 years after myocardial infarction in patients with a high risk of atherothrombotic complications and confirmed the expediency to reduce the dose of ticagrelor from 90 to 60 mg twice daily for 1 year after the onset of the disease to ensure the best balance of efficacy and safety of treatment. The possibility of prolonging double antiplatelet therapy using a combination of ASA and ticagrelor at a dose of 60 mg twice daily for 1 year after myocardial infarction is provided for in the guidelines for medical use of ticagrelor and is enshrined in existing clinical guidelines. Presently, ticagrelor is the only P2Y12 platelet receptor inhibitor approved in the Russian Federation as an adjunct to ASA for the long-term prevention of atherothrombotic cardiovascular events.

30-43 590
Abstract

Introduction. Multifocal atherosclerosis (MFA) in patients with CHD is a key risk factor for thrombotic complications (TC). There are little data on the long-term prognosis in patients with multivessel CHD combined with carotid artery lesions.
Objective. To assess prognostic negative outcomes (thrombosis and bleeding) in patients with CHD and MFA undergoing revascularization procedures – coronary artery bypass graft surgery and, in case of high risk of ischemic stroke, carotid endarterectomy.
Materials and methods. A total of 189 patients with stable multivessel coronary artery disease who successfully underwent coronary bypass graft surgery and had concomitant atherosclerosis of the carotid arteries ≥50% were included in the study. The exclusion criterion was chronic use of oral anticoagulants. The choice of antithrombotic therapy after the surgical intervention was determined by the attending physicians. The efficacy endpoint was defined as the sum of TC including cardiovascular death, acute coronary syndrome, ischemic stroke, acute lower limb ischemia, and the need for emergency revascularization of the carotid or coronary basins. BARC bleeding types 2-5 were considered as a safety endpoint.
Results. The median follow-up period was 37 months. [MR 25.0; 45.0]. The cumulative incidence of TC was 11.1%, BARC 2-5 bleeding was 4.8%. One or two antiplatelet agents were prescribed at discharge in 87.3% of cases, and in 12.7% – a combination of acetylsalicylic acid (ASA) and oral anticoagulant (OAC) for up to 6 months. The incidence of thrombotic complications was not significantly different in the mono- or dual antiplatelet therapy groups. The combination therapy group (OAC + ASA) was characterized by the highest number of comorbidities. When analyzing the TC for the first 6 months. (before anticoagulant withdrawal) there was no significant difference between the groups of antiplatelet therapy and the combination of ASA and OAC (Log-Rank, p = 0.4669). The proportion of patients who survived the entire follow-up period without developing TC was significantly higher in the group compared to the initial combination therapy group: 0.83 versus 0.50 (Log-Rank, p = 0.0101).
Conclusion. Despite complete revascularization, the incidence of TC during the two years of follow-up was high. In the combination therapy group, anticoagulant withdrawal led to an increased incidence of TC.

44-54 499
Abstract

Introduction. Pulmonary embolism (PE) accounts for about 10% in the mortality pattern among cancer patients, which is the second most frequent cause of death.
Aim. To identify and characterize patients with active cancer and VTEC receiving chemotherapy (CT) based on the retrospective review of medical records provided by Moscow City Oncology Hospital No. 62 (MCOH No. 62) for the period from 01.2018 to 04.2020.
Materials and methods. Medical records of 3,912 patients receiving chemotherapy treatment cycles in the departments of MCOH No. 62 were reviewed. 227 (5.8%) patients in whom the underlying disease course was complicated by VTEC were selected. Sites of primary tumours, n (%): stomach – 37 (16.3); colon and rectum – 36 (15.9); uterus, cervix, ovaries – 31 (13.7); lungs – 23 (10.1); kidneys, ureters and bladder, testicles – 19 (8.4); pancreas – 18 (7.9); soft tissues – 14 (6.2); mammary gland – 13 (5.7); lymphoma, myeloma – 8 (3.5); Ear Nose Throat (ENT) tumours – 7 (3); others – 21 (9.3).
Results. The majority of patients (176 (77.5%)) had a sum Khorana score <3, 51 (22.5%) patients had Khorana scores ≥ 3, which corresponds to a high thrombotic risk. 29 (12.7%) patients died. The hospital physicians assessed the causes of death as follows: 16 patients died from pulmonary embolism, of which 13 (81%) had a sum Khorana score <3; 13 patients died due to progression of cancer.
Conclusions. VTEC most commonly occurred in patients with gastrointestinal cancer (32.2%) and genito-urinary system cancer (22.1%). Half (54.5%) of VTEC occurred in the first 3 months of chemotherapy treatment. The Khorana scale is non-perfect in ‘real-life’ clinical practice (only 22.5% of patients with verified VTEC had a high thrombotic risk, and 81% of patients who died due to PE had a low and medium risk of VTEC).

HYPOLIPIDEMIC THERAPY

56-75 562
Abstract

According to the latest international and Russian guidelines for the treatment of dyslipidemias, statins are defined as the main group of drugs that significantly reduce the level of low-density lipoprotein cholesterol (LDL-C) effectively prevent atherosclerotic cardiovascular diseases (CVD) and complications and can slow down the progression of atherosclerosis. The principle “the lower LDL-C, the better” is especially relevant in categories of patients with very high and extreme cardiovascular risk, and therefore, in order to achieve target LDL-C values (≤1.4 is optimal ≤1.0) in this category of patients, high-intensity lipid-lowering therapy should be used. Rosuvastatin remains the most effective statin. Its use makes possible to achieve target lipid values at the starting dose of treatment, enhances adherence to treatment, and also reduces the frequency of side effects associated with the use of high doses of other statins. In addition, the proven ability of rosuvastatin to reduce the volume of atherosclerotic plaque, by reducing the level of pro-inflammatory cytokines and C-reactive protein, normalizing endothelial function, antiplatelet action, that is, rosuvastatin, in addition to its powerful lipid-lowering effect, has anti-inflammatory and anti-ischemic effects. Also, rosuvastatin can be successfully used in the presence of comorbidities, including chronic kidney disease and chronic heart failure. Taking into consideration the urgency of the fight against the COVID-19 pandemic (coronavirus Disease 2019), which covered 220 countries, due to the lack of effective etiotropic drugs, the possibility of using statins, including rosuvastatin, for the treatment of comorbid patients with COVID-19, was evaluated.

SURGICAL MANAGEMENT

76-86 391
Abstract

This article presents modern possibilities for the provision of emergency surgical care to patients with atrial fibrillation, who administered dabigatran etexilate. We describe two clinical situations, in which idarucizumab, a specific dabigatran antagonist, which is a monoclonal antibody fragment that binds dabigatran, was used to neutralize the anticoagulant effect of dabigatran etexilate before emergency surgery. In the first case, the patient developed acute gangrenous calculous cholecystitis, in the second a patient required an urgent epicystostomy. In both cases, the successful outcome of surgical interventions was due to the effective interactions of the team of specialists and adherence to the algorithm for providing emergency care to such patients, as well as the presence of idarucizumab in hospitals. The postoperative management of patients and the timely resumption of anticoagulant therapy to prevent thromboembolic complications is no less important. The presented clinical cases confirm the feasibility of using idarucizumab to provide emergency surgical care to patients on dabigatran etexilate, as well as the need to take into account the possible risk of emergency interventions when anticoagulant therapy is prescribed to patients with atrial fibrillation. This paper discusses special risk groups of patients in whom rapid reversal of anticoagulation is required due to altered hemostasis.We outline data of a prospective cohort study (RE-VERSE AD), which examined the efficacy and safety of idarucizumab in patients with uncontrolled bleeding and in patients requiring urgent surgery. We also present the RE-VECTO study data on the use of idarucizumab in real-life clinical practice.

88-93 403
Abstract

In this study we present a clinical case of simultaneous surgical treatment of a patient with an abdominal aorta aneurysm and cholelithiasis. Such a combination of diseases is rather common, but few centres have experience in performing simultaneous operations. In the literature, one can usually find observations or descriptions of small series of operations. The potential risk of infection of a synthetic prosthesis due to contamination of the prosthesis during cholecystectomy is one of the most significant constraining factors for performing simultaneous operations. Review of the available literature showed that most of the authors who promoted the staged treatment of this group of patients adhered to this position. On the other hand, dividing the treatment of two diseases into stages may be associated with specific complications of unoperated pathology. For instance, some authors described cases of aortic aneurysm rupture after cholecystectomy. On the other hand, there are publications that indicate the association between exacerbation of gallstone disease and resection of the aortic aneurysm. Contradicting outcomes and different points of view on potential risks associated with simultaneous and staged treatment approaches for this group of patients require analysis and determination of the optimal surgical technique to minimize the risks of infectious complications, aortic aneurysm rupture and exacerbation of cholelithiasis. Based on the presented observation and the other authors’ review of the outcomes, we concluded that the simultaneous operations can be performed without risk. The compliance with a stage-by-stage approach to the operation which will minimize the risks of infection of the prosthesis is the main condition for the safe performance of such operations.

DISCUSSION

94-102 2637
Abstract

This article presents a critical analysis of the results of three prospective randomized controlled trials of anticoagulant use in patients with superficial vein thrombosis of lower limbs CALISTO using fondaparinux sodium, STEFLUX using different doses of parnaparin sodium, and SURPRISE comparing the effectiveness and safety of fondaparinux sodium and the preventive dose of the oral anticoagulant rivaroxaban.
Evidence from these clinical trials suggests that low-dose anticoagulants should be used for at least 1.5 months in superficial vein thrombosis of lower limbs with thrombus localization beyond 3 cm from the saphenofemoral and/or saphenopopliteal junction. However, anticoagulant treatment does not appear to prevent the progression of venous thrombosis after withdrawal, so in patients with persisting risk factors, it is reasonable to consider extended treatment. This seems to apply primarily to patients with superficial thrombophlebitis a history of superficial or deep venous thrombosis in the lower extremities, a family history of venous thromboembolic complications, and possibly a broader contingent of high-risk patients, not represented in the CALISTO and STEFLUX studies (with active malignancy, ongoing anticancer therapy, severe chronic heart or respiratory failure, inability to withdraw hormone replacement therapy, autoimmune disease). According to the accumulated evidence, subcutaneous injections of fondaparinux sodium, intermediate doses of low molecular weight heparin, and direct oral anticoagulant rivaroxaban in the dose of 10 mg once a day are effective and sufficiently safe in the treatment of superficial vein thrombosis of lower limbs with localization beyond 3 cm from the saphenofemoral and/or saphenopopliteal junction. Questions about the feasibility of increasing the doses of anticoagulants to further reduce the rate of superficial thrombophlebitis - progression during treatment and the optimal duration of their use remain open.

CLINICAL ANALYZES

103-120 575
Abstract

As established today by a number of studies, transferred COVID-19 (even mild) is associated with a high risk of delayed heart damage. Although human coronaviruses are a minor cause of all cases of viral myocarditis, they have been associated with myocarditis in patients of all age groups. Post-COVID-19 myocarditis can be manifested by heart failure, heart rhythm and conduction disorders. A case report of 14-day hospitalization of an 89 y.o. man for a life-threatening myocardial conduction disorder – complete AV block – on the background of a permanent form of Arial fibrillation, accompanied by clinical death of the patient, coagulopathy, nosocomial pneumonia, heart failure and impaired consciousness. During the treatment, which included cardiopulmonary resuscitation, the use of temporary and then permanent pacemaker, antibiotics, levocarnitine, Fondaparinux, blood clot transfusions for profound thrombocytopenia, led to the restoration of heart rhythm and conduction, reduction of heart failure, cure of nosocomial pneumonia and restoration of exercise tolerance. Post- COVID-19 complications are currently still weakly understood and poorly predicted, but their treatment according to the general rules gives positive results. In patients with heparin-induced thrombocytopenia, as in patients with initial thrombocytopenia (including after COVID-19 conditions), it is advisable to use the drug Fondaparinux, which has proven itself in the prevention and treatment of arterial and venous thromboembolism. In the treatment of posthypoxic complications, it is appropriate to use Levocarnitine to correct post-ischemic changes in the myocardium and brain.

122-134 506
Abstract

A fatal case of severe stenosis of the aortic orifice in a patient with not diagnosed in time, long-term persistent covid infection is presented. The patient was hospitalized to resolve the issue of surgical correction of the aortic stenosis. On admission, there were symptoms of circulatory failure at the level of 3–4 functional class according to NYHA and angina pectoris clinic. A detailed collection of anamnesis about the epidemiological environment and symptoms of pneumonia suffered in the fall of 2020 raised suspicions of its covid genesis. Subsequently, this assumption was confirmed by the data of laboratory, instrumental studies, as well as the results of the pathological and anatomical autopsy. The study of microslides showed signs of extensive vasculitis with thrombosis of small branches of the pulmonary artery and foci of pneumofibrosis of various degrees of prescription, which also testified in favor of the transferred covid infection. Taking into account the severity of the patient’s condition upon admission, it was not possible to perform emergency intervention on the aortic valve. After stabilization of the state and regression of the phenomena of circulatory failure, it was planned to simultaneously perform endovascular revascularization of the coronary valve bed and transcatheter aortic valve replacement. The planned surgical intervention failed. The immunosuppressive effect of the SARS-CoV-2 virus, apparently, led to the activation of autoflora and an increase in inflammation for nosocomial infection. Bilateral polysegmental bacterial pneumonia that joined during hospitalization, against the background of postcoid changes in the lung parenchyma, contributed to the development of acute coronary syndrome with ventricular arrhythmias. The patient died from acute cardiopulmonary failure. The article also presents ideas about the operational tactics of managing patients with aortic stenosis in a pandemic.



ISSN 2307-1109 (Print)
ISSN 2658-5952 (Online)