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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.

Introduction. Despite the large evidence base for the use of rivaroxaban, cohort studies are interesting because shows the possibility of anticoagulant therapy in patients with high thromboembolic and bleeding risk and a burden of comorbidity in practice.Aim: to evaluate the efficacy and safety of rivaroxaban therapy in patients with atrial fibrillation in prospective REGATTA registry.Materials and methods. This study is a fragment of a single-center prospective REGATA registry (Registry of Long-term Antithrombotic Therapy (NCT043447187), conducted on the basis of the National Research Center of Cardiology of the Ministry of Health of the Russian Federation. 152 patients with high thromboembolic risk (median CHA2DS2-VASc = 4) received rivaroxaban therapy (median follow-up 1.5 years). The efficacy endpoint was the sum of cardiovascular complications (including cardiovascular death, ischemic stroke, and acute coronary syndrome). The safety endpoint bleedinds BARC types 2-5.Results. The frequency of cardiovascular events (combining cardiovascular death, ischemic stroke and acute coronary syndrome) was 5.8/100 patient-years. The use of a “reduced” dose of rivaroxaban was an independent predictor of the development of fatal cardiovascular complications. The rate of major bleeding was 3.7/100 patient-years, and the rate of clinical relevant bleedings was 19.4 /100 patientyears. The predictors of major/ clinical relevant bleedings were chronic kidney disease with a decrease in creatinine clearance of less than 50 ml/min and the anamneses of major/ clinical relevant bleedings.Conclusion. The main requirement for improving the safety of anticoagulants is follow up, focused in all changes in the cardiovascular and somatic status of the patient during treatment.

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.

This review systematizes the currently known data on intracardiac thrombosis. The main nosology leading to left atrial thrombosis is atrial fibrillation, with up to 90% of all trombi forming in the left atrial appendage. The optimal method to diagnose thrombosis is the transesophageal echocardiography. The detection rate of left atrial appendage thrombosis in early studies ranged from 2.5 to 74.7% and dropped to 1-15.2% in the era of oral anticoagulants. However, there is no basis for performing transesophageal echocardiography as a screening examination for all patients with atrial fibrillation, and the CHA2DS2-VASc clinical scale is the guideline for prescribing and selecting antithrombotic therapy. The article presents data on the possibility of lysis of the left atrial appendage thrombosis against the background of oral anticoagulants therapy, which is of practical importance for patients before cardioversion and pulmonary vein ablation. The results of published studies and observations of patients receiving vitamin К antagonists show that 46.3-85% of thrombi are dissolved. The only prospective study to investigate the possibility of left atrial thrombosis lysis in patients with atrial fibrillation or fluttering while taking direct oral anticoagulants was X-TRA, which studied rivaroxaban therapy and showed thrombi dissolution in 41.5% of patients. The frequency of left ventricular thrombosis in patients with acute coronary syndrome with ST segment elevation in the age of reperfusion therapy is about 6-7%, reaching 19.2% in patients with anterior myocardial infarction and reduction of left ventricular ejection fraction. These recommendations indicate that only vitamin К antagonists may be prescribed in patients with left ventricular thrombosis. However, the results of the COMMANDER HF study showing the potential of rivaroxaban to prevent thromboembolic complications in patients with chronic heart failure have laid the foundation for the use of direct oral anticoagulants in left ventricular thrombosis. At present the study of efficacy and safety of apixaban and rivaroxaban in this category of patients is ongoing, but there are no results at present. In most cases, right ventricular thrombosis is part of the development of a pulmonary embolism, and much less often it accompanies right ventricular arrhythmogenic dysplasia or is associated with implantable devices. Anticoagulants are the basis for the treatment of these patients, and the present guidelines allow for moderate and low risk thromboembolism in patients with pulmonary artery thromboembolism, along with parenteral anticoagulants, prescribing immediate oral anticoagulants, giving preference to Xa-factor antagonists or direct thrombin inhibitors.

Aim. To study the predictive value of growth differentiation factor 15 (GDF-15) in patients with atrial fibrillation (AF) after elective percutaneous coronary intervention (PCI).Material and methods. The study included 150 patients (men, 69,3%) with AF receiving direct oral anticoagulants in combination with two (89,3%) or one antiplatelet agent (10,7%) after elective PCI. Median age was 71,0 [interquartile range, 66,0; 77,0] years. The median follow-up was 11,5 months [interquartile range, 8,0; 12,0]. The efficacy endpoint was the sum of cardiovascular events (CVEs), including cardiovascular death, ischemic stroke, venous thromboembolism, peripheral arterial thrombosis, acute coronary syndrome, and the need for emergency PCI. The safety endpoint was considered to be BARC type 2-5 bleeding. Prior to PCI, blood plasma samples were taken from patients to determine GDF-15 and D-dimer by enzyme immunoassay.Results. The incidence of CVEs was 16%. The incidence of BARC type 2-5 bleeding was 24,7%. The median GDF-15 level was 1270,0 pg/ml [953,0; 1778,0]. According to multiple regression, the GDF-15 level is associated with D-dimer (t=3,20; p=0,0018), diabetes (t=3,97; p=0,0001) and SYNTAX score II (t=4,77; p1191 pg/ml (p=0,0076) increases the likelihood of CVE (area under the curve, 0,647; confidence interval (CI), 0,5650,723). According to Kaplan-Meier survival curves, significant differences were found in terms of absence of CVEs during the follow-up period between the groups of patients with a GDF-15 >1191 and those with GDF-15 Conclusion. GDF-15 is a novel marker of CVE in AF patients after elective PCI.

Russian Society of Cardiology (RSC).With the participation of Russian Scientific Society of Clinical Electrophysiology, Arrhythmology and Cardiac Pacing, Russian Association of Cardiovascular Surgeons.Approved by the Scientific and Practical Council of the Russian Ministry of Health.

Rationale: Thrombosis of the puncture site in the femoral veins is one of the potentially dangerous complications of intracardial catheter interventions associated with thromboembolic risk related to its proximal location. According to the literature, the incidence of symptomatic venous thrombosis (VT) is 1–3%. No special studies on the assessment of risk factors for this complication, its diagnosis and treatment have been conducted.Aim: To study the incidence, risk factors and special aspects of VT diagnosis in patients undergoing intracardial electrophysiological studies (EFI) and/or catheter ablation.Materials and methods: This prospective study included 408 patients (194 men and 214 women, with median age of 51±10.1 years), who were admitted to the hospital with various cardiac rhythm disorders for intracardial EFIs and/or catheter ablations from 2016 to 2018. Before the interventions, in addition to common laboratory and instrumental work-up, all the patients underwent ultrasound duplex scanning (USDS) of the iliac-femoral segment; in 269 patients the level of D-dimer was measured. Latest at 24 hours after the intervention, all patients underwent a control ultrasound scan of the femoral vein puncture site. In case of VT occurrence anticoagulant therapy was started in all patients and they were followed up till complete VT resolution and at least for 3 months (the study endpoint). The VT incidence and its risk factors including the prognostic value of D-dimer levels were evaluated.Results: The VT incidence after catheter interventions was 11.7% (n=48). There was a significant correlation between VT occurrence and such risk factors as diabetes mellitus (p=0.001) and obesity (p500 ng/mL) and subsequent VT development was found (p>0.05). The quartile analysis revealed an association between baseline D-dimer levels exceeding 434 ng/mL (which corresponds to the range of 75 to 100%) and the presence of the following risk factors: age over 65 years (pConclusion: In this study, all VTs (11.7%) detected after catheter transvenous interventions by USDS were asymptomatic. VTs were most frequent in patients with diabetes mellitus and obesity. D-dimer had no predictive value in the development of VT; however, its increased baseline values were more common in women, patients over 65 years, and in patients with arterial hypertension and chronic coronary heart disease.

The use of modern oral anticoagulants is associated with a significant reduction in the risk of stroke and systemic embolism in patients with atrial fibrillation, and thus with an increase in the life expectancy of patients. That is why multicomponent therapy and perioperative tactics are actual during prolonged anticoagulation, the aspects of which seem to be one of the most difficult from the practical point of view. This clinical observation is an illustration of the management of a patient with atrial fibrillation at high thromboembolic risk who is receiving Rivaroxaban therapy and who has indications for catheter ablation and multicomponent antithrombotic therapy.

to compare two anticoagulant therapy (ACT) regimens in the treatment of venous thrombosis (VT) in patients after catheter interventions - electrophysiological studies (EFIs) and ablations: enoxaparin followed by warfarin, and rivaroxaban monotherapy.The study included patients from 18 years and older with heart rhythm disorders and planned catheter ablation. When parietal venous thrombosis (VT) were detected at the femoral vein puncture site, all patients were randomly assigned to two treatment groups. In group I enoxaparin 1 mg/kg was prescribed every 12 hours with switching to warfarin after 7 days with maintenance of the target INR values (2.0-3.0). In group II rivaroxaban therapy was started at a dose of 15 mg twise/day for 21 days with a further transition to a dose of 20 mg/day. The total period of observation and treatment of patients was at least 3 months.408 patients were observed, 42 (10.3%) patients with parietal VT were divided into two treatment groups. In group I (n=16) complete lysis of VT was noted by the 7th day of treatment in 7 (58.3%) patients, however this scheme was associated with a greater risk of complications (р=0.003) at the puncture site in the form of arteriovenous fistulae (n=1; 8.3%) and intermuscular hematomas (n=4; 25%). In group II (n=26), no complications were noted, the lysis time of VT was on average 21 days (n=18; 69.2%). Complete lysis of VT was noted in both groups at the time of the control observation point (3rd month).The efficiency of the two VT treatment regimens was comparable. Enoxaparin therapy is associated with a high risk of local complications, namely intermuscular hematomas (n=4; 25%) and arteriovenous fistulas (n=1; 8.3%). Rivaroxaban monotherapy is safer (p=0.003); in Group II none of the patients had any complications.Цель исследования: сравнить две схемы антикоагулянтной терапии (АКТ) в лечении венозных тромбозов (ВТ) у пациентов после внутрисердечных катетерных вмешательств - электрофизиологических исследований (ЭФИ) и абляций: эноксапарина с последующим назначением варфарина и монотерапии ривароксабаном. Материалы и методы. В исследование включали пациентов от 18 лет с нарушениями ритма сердца и планируемыми катетерными вмешательствами. При выявлении пристеночного ВТ в месте пункции бедренной вены пациентов рандомизировали на две группы лечения: в группе I проводилась АКТ эноксапарином 1 мг/кг каждые 12 ч с переходом на варфарин через 7 дней с поддержанием целевых значений международного нормализованного отношения (2,0-3,0), в группе II - АКТ ривароксабаном 15 мг 2 раза/сут в течение 21 дня с дальнейшим переходом на дозу 20 мг/сут. Срок наблюдения и лечения пациентов составил 3 мес. Результаты. Наблюдали 408 пациентов, из них 42 (10,3%) пациента с пристеночным ВТ распределили на две группы лечения. В группе I (n=16) у 7 (58,3 %) больных отмечен полный лизис ВТ к 7-му дню лечения, однако эта схема сопряжена с большим риском осложнений (р=0,003) со стороны места пункции в виде артериовенозных соустий (n=1; 6,25%), межмышечных гематом (n=4; 25%). В группе II (n=26) осложнений не отмечалось, время лизиса ВТ в среднем составило 21 день (n=18; 69,2%). В обеих группах на момент проведения контрольной точки наблюдения (3-й месяц) отмечен полный лизис ВТ. Заключение. Эффективность двух схем лечения ВТ оказалась сопоставимой. Терапия эноксапарином сопряжена с большим риском развития местных осложнений: межмышечных гематом (n=4; 25%), артериовенозных соустий (n=1; 8,3%). Монотерапия ривароксабаном была более безопасна (р=0,003), в группе II осложнений не отмечено.

Assessment of kidney function is mandatory in all cardiac patients, and patients with atrial fibrillation represent a category of patients with high thrombotic risk, which increases the risk of decreased kidney function during follow-up. Controversial issues of warfarin-associated nephropathy are important today. A prospective 5-year follow-up of 172 patients receiving warfarin therapy showed that 26.7% had the sudden loss of renal function (SLRF) (defined as an annual decline in glomerular filtration rate (GFR) ≥ 3 ml/min/1.73 cm2). Based on the results of the ROC analysis, it was determined that the maximum INR > 3.97 was associated with the SLRF (the area under the curve was 0.649, the sensitivity 56.5%, the specificity 74.6%, p = 0.003), and the maximum INR> 6.0 increased the specificity of the analysis to 96%. The study showed that for patients who had a maximum INR value ≥ 3.97, the mean delta of changes in GFR was negative, and the largest negative dynamics was characteristic for patients with a maximum INR ≥ 6.0. The estimated odd ratio of SLRF confirms the high prognostic significance of the maximum INR value. The maximum INR 3.97-5.9 increased the risk of SLRF by 3.07 times (95% CI 1.5241-6.2017, p = 0.0017), as well as the INR ≥ 6.0 (OR 3.05, 95% CI 1.0073-9.2433, p = 0.0485). The multifactorial discriminant analysis showed that the SLRF predictors against the background of 5-year warfarin therapy included the maximum INR ≥ 3.97 (F = 10.45, p = 0.0014), IHD (F = 8.7, p = 0.0036), diabetic nephropathy (F = 5.29, p = 0.0226) and the CHA2DS2-VASc score ≥ 4 (F = 5.05, p = 0.0258).

Atrial fibrillation (AF) is the most common indication for the long-term oral anticoagulation therapy. For several decades, vitamin K antagonists have been the mainstay of routine clinical practice.A prospective 10-year follow-up of patients with atrial fibrillation receiving warfarin therapy showed that the incidence of all cerebral circulation disorders was 2.59 per 100 patient-years. The warfarin therapy contributed to the prevailing of non-fatal events among the cerebral circulation disorders which occurred during the therapy. The incidence of fatal ischemic strokes was 0.91 per 100 patient-years over the 10-year follow-up study.If the duration of a patient within the target therapeutic range (TTR) was

Despite the long-term clinical experience, bleeding remains the greatest danger for patients taking vitamin K antagonists. Moreover, even the presence of risk factors for hemorrhagic complications in a patient should not be the only reason for cancelling anticoagulant therapy. The challenge in assessing the frequency of hemorrhage is primarily explained by different approaches to hemorrhage classification. For patients receiving long-term anticoagulant therapy, along with fatal and life threatening hemorrhages, minor and clinically significant small hemorrhages should be taken into account to assess the safety of treatment. The 15-year prospective follow-up of patients receiving warfarin found that the frequency of all hemorrhagic complications was 8.66/100 patient-years, major hemorrhage — 2.98/100 patient-years, and clinically significant hemorrhage — 2.62/100 patient-years. According to the results of the discriminant analysis, the predictors for the development of major and clinically significant hemorrhagic complications in patients receiving long-term therapy with warfarin are administration of proton pump inhibitors, labile INR during therapy, recurrent minor hemorrhage in history and amiodarone therapy. The 15-year prospective follow-up of patients receiving warfarin demonstrated that minor hemorrhagic complications account for one third of all bleedings and are not associated with the subsequent development of clinically significant and major bleeding in patients. The prospective follow-up also found an increase in the frequency of hemorrhagic complications if one or two antiplatelet agents were added to warfarin therapy. The incidence of major and minor clinically significant hemorrhagic complications during triple antithrombotic therapy was 24/100 patient-years, which was higher than in the warfarin monotherapy subgroups and in the case of combining warfarin with an antiaggregant (4.4 and 8.47%, respectively). The localization of bleeding was analyzed to reveal that in triple antithrombotic therapy the greatest number of bleedings occurred in the upper or lower gastrointestinal tract. The relative risk was calculated to confirm that triple antithrombotic therapy significantly increased the risk of gastrointestinal bleeding by 3.02 times.

For patients with atrial fibrillation, long-term oral anticoagulant therapy reduces the risk of ischemic stroke and systemic embolism, while increasing the risk of hemorrhagic complications. To assess the safety of therapy, along with major bleeding, minor and clinically relevant bleeding also should be taken into account. Minor, especially recurrent hemorrhages usually do not provide a reason for discontinuing anticoagulant therapy. The described follow-up demonstrated the absence of major hemorrhage in the patient with recurrent minor hemorrhagic complications against a background of 15-year course of anticoagulant therapy (including 9-year course of dabigatran treatment).

In a question-and-answer format, the most critical issues concerning the safety of therapy and management of patients taking dabigatran are considered in the article. Particular attention is paid to the prospects of anticoagulant therapy in patients with comorbidities, as well as interactions between novel oral anticoagulants and other groups of medications, risk assessment of potential complications of therapy.

The paper discusses the most common questions regarding the safety of therapy and patronage system in patients who receive warfarin in the question and answer form. Vitamin K antagonists now are the oral anticoagulants that are most commonly used in the actual clinical practice. Despite a large accumulated body of clinical experience, it is not always easy for a doctor to pick the individual dose of warfarin.

Aim of the study was to elucidate value of HAS-BLED and HEMORR2HAGES scales for prediction bleedings in patients receiving long-term warfarin (W) therapy.The study involved 119 patients (72 men) aged 60.9 ± 9.6 years with atrial fibrillation or venous thromboembolic complications. Follow up period was 5.6 ± 3.4 years. All bleedings were categorized as 1) single bleeding with INR4.0 during the 1st month of W therapy; 2) any single bleeding after 1st month of W therapy; 3) recurrent bleedings. CYP2C9 and VKORC1 (G3673A) genotypic variants were determined by PCR. Patients were divided into low (3 points of HAS-BLED scale, n = 58;4 points of HEMORR2HAGES scale, n = 109) and high (3 points of HAS-BLED scale, n = 61, ≥ 4 points of HEMORR2HAGES scale, n = 10) bleeding risk groups.There was no relationship between total HAS-BLED, HEMORR2HAGES scores and numbers of all as well as category 1 and 2 bleedings. The difference in bleeding frequency between high and low risk groups was significant only for recurrent bleedings. There were 22 (36.1%) and 5 (8.6%) recurrent bleedings among 61 and 58 patients with high and low-risk HAS-BLED score, respectively (p = 0.0048). Recurrent bleedings also occurred more frequently among patients with high risk (7/10, 70%) compared with low risk (20/109, 18.35%) HEMORR2HAGES score (p = 0.018). Subgroups of high and low bleeding risk according to HAS-BLED and HEMORR2HAGES scores differed only by proportion of patients with recurrent bleedings. High W sensitivity represented by 2*/2*, 2*/3*, 3*/3* CYP2C9 and/or AA VKORC1 homozygosis was detected in 25 of 119 patients. Six of 8 patients (75%) with category 1 bleedings were carriers of any polymorpism.HAS-BLED and HEMORR2HAGES scales performed best in predicting recurrent bleedings in patients on long term W therapy. Single bleedings with INR4.0 during 1st month of W therapy were associated with reduced W metabolism (AA VKORC1 or/and CYP2C9 allelic variants 2*/2*, 2*/3*, 3*/3*).

The safety of anticoagulant therapy is discussed. Warfarin position in prevention of thrombotic complications is analyzed according to the evidence base medicine approach. Possible hemorrhagic complications of warfarin are described and accompanied with clinical cases. Possibility of renewal of anticoagulant therapy in patients after hemorrhagic complications is discussed.

The study included 25 patients at high risk of thromboembolic complications. All of them were treated with acenocoumarol for 6 months under control of the frequency of hemorrhage and episodes of severe hypocoagulation (a more than 3-fold rise in INR). All the patients underwent CYP2C9 and VKORC1 genotyping. It was shown that the presence of CYP2C9*2 and CYP2C9*3 alleles in the CYP2C9 locus and the AA genotype of the polymorphous G-1639(3673)A marker of the VKORC1 gene was not associated with the development of severe hypocoagulation episodes (p = 0.261--for CYP2C9, p = 0.616 and 0.361 for VKORC1 in the total group and a subgroup of patients having the CYP2C9*1/*1 genotype respectively and treated with acenocoumarol. The search for other genetic markers of efficacy and safety of this drug should be continued.

Aim of the study was to compare numbers of episodes of excess hypocoagulation and bleeding with warfarin dosing based on pharmacogenetic testing and traditional method in patients with high risk of thromboembolic complications. In 76 patients (43 men and 33 women aged 60.3 +/- 12.3 years) warfarin was administered starting with the dose calculated according to the gage algorithm with consideration of results of pharmacogenomic testing (genotyping of CYP2C9 and VKORC1). Control group comprised 78 patients aged 63.4 +/- 9.4 years who had participated in an earlier retrospective study in which they received warfarin according to traditional scheme with starting dose of 5 mg/day. In both groups we analyzed data obtained during 6 months after start of drug administration. Genotyping was carried out by polymerase chain reaction. Episodes of excess hypocoagulation (international normalized ratio above therapeutic range) and bleeding accurred more rarely with the use of pharmacogenetic approach to dosing of warfarin compared with standard method (17.1 vs 56.4%, p = 4.1 x10(-7), and 4 vs 18%, p = 0.009 respectively).

Aim of the work was selection of optimal for patients in Russia algorithm of warfarin dosing based on results of pharmacogenomic testing. We analyzed data from 78 patients aged 63.4+/-9.4 years with known CYP29 and VKORC1 genotypes who had participated in an earlier retrospective study in which they received warfarin according to traditional scheme with starting dose of 5 mg/day. We used 5 known algorithms of determination of initial warfarin dose based on results of pharmacogenomic testing and correlated calculated doses with those which had been actually selected in our patients. Correlation was closest for doses obtained with algorithm of Gage et al (www.warfarindosing.org) (r=0.887, p0.0001). Therefore we consider this algorithm most suitable for patients in Russia.

Aim of the study was to investigate frequency and influence of alleles CYP2C9*2 and CYP2C9*3 on pharmacokinetics, pharmacodynamics and dosing regimen of warfarin and on development of hemorrhagic complications. We included 84 patients (mean age 62,8 +/- 10,5 years). Duration of follow-up varied between 1 month and 1 year. Carriage of allele variants was determined by polymerase chain reaction, measurement of plasma wafarin concentration was carried out with the help of high performance liquid chromatography. Wild type (CYP2C9*1/*1) was found in 68% of patients; overall frequency of 2C9*1/*1, *l/*3, *2/*2, *3/*3, *2/*3 genotypes was 32%. Average maintenance doses of warfarin for patients with allele variants CYP 2C9 *2 and 2C9 *3 were 3.6 and 3.1 mg/day, respectively, what was significantly lower than in wild type homozygotes (6.1 mg/day). Wild type homozygotes (1) had the highest warfarin clearance (3,51 ml/min). In carriers of 2C9 *2(2) and 2C9 *3(3) warfarin clearance was significantly lower (2.42 and 1.82 ml/min; p1 - 2 = 0,05; p1 - 3 = 0,0008). In carriers of allele variants CYP2C9*2, CYP2C9*3 values of international normalized ratio3,0 were met more often, especially in carriers of CYP2C9*3 (in 100% of cases) vs. 28% in wild type homozygotes (p=0,02). Carriers of CYP2C9*3 compared with wild type homozygotes had more hemorrhagic complications (67% and 16%, respectively, p=0,0008). Thus cytochrome P450 2C9 gene polymorphism influences frequency of development of hemorrhagic complications, metabolic clearance, and magnitude of warfarin maintenance dose.

Patients with atrial fibrillation taking either indirect anticoagulant acenocumarol or most often prescribed antiaggregant aspirin were followed for 1 year. The results have shown that therapy with acenocumarol lowers content of D-dimer, prevents formation and promotes lysis of left auricular thrombi and lowers risk of development of ischemic stroke in patients with atrial fibrillation and high risk of thromboembolism. Therapy with aspirin in a dose providing maximal suppression of platelet function, does not lower D-dimer levels, does not promote lysis of left auricular thrombi and is inferior to acenocumarol in prevention of ischemic stroke.

CYP2C9 is the main enzyme participating in warfarin metabolism, of which genetic polymorphism is typical. The aim of the study was to investigate the influence of having allelic variants CYP2C9*2 and CYP2C9*3 on the pharmacokinetics, dosage regimen, and the rate of hemorrhage in patients with constant atrial fibrillation taking warfarin. Eighty-two patients with constant atrial fibrillation taking warfarin were included in the study. It was shown that in patients with CYP2C9*2 and CYP2C9*3 the clearance of warfarin and its dose were lower, while the episodes of excessive hypocoagulation and hemorrhage associated with warfarin were more frequent than in patients without these allelic variants. Basing on the results of the study, the authors propose an algorithm of choosing the initial warfarin dose depending on CYP2C9 genotype.

The review is devoted to the contemporary state of the problem of pharmacogenetics of indirect anticoagulants. At present there are data about effects of allele variants of CYP2C9, VKORC1, APOE genes on efficacy and safety of therapy with indirect anticoagulants. Detection of these variants is a perspective way to individualization of therapy with indirect anticoagulants.

Thromboembolic complications (cerebral infarction and system embolism) are the most threatening ones in patients with ciliary arrhythmia without valvular lesions. Transoesofhageal echocardiography is the method of choice in detection of left atrial auricle thrombosis, which is the main source of thromboembolism in this category of patients. Primary and secondary prevention of thromboembolic complications in patients with ciliary arrhythmia is a topical problem, still remaining unsolved. Administration of indirect anticoagulants, which are the preparations of choice, demands strict doctor's supervision and continuous laboratory monitoring. The study presents authors' own data, based upon the observation of patients treated with either warfarin or acenocumarol. The paper demonstrates equal efficiency of both cumarine anticoagulants. The frequency of haemorrhagic complications after 12-month therapy with either warfarin or acenocumorol in patients with ciliary arrhythmia without valvular lesions was comparable. Warfarin provided more stable level of anticoagulation and thus long-term warfarin therapy was characterized by lower risk of complication.

To assess frequency of left auricular thrombosis and effect of long-term therapy with acenocoumarol on auricular hemodynamics and system of hemostasis and to elucidate predictors of effective therapy with acenocoumarol in patients with nonvalvular atrial fibrillation.Patients (n=100) with nonvalvular atrial fibrillation and at least 1 risk factor of thromboembolic complications.Transesophageal echocardiography and measurement of blood D-dimer levels were carried out before and after 1 year of acenocoumarol therapy.Initial prevalence of left auricular thrombosis was 75%. The use of acenocoumarol for 12 months resulted in significant reduction of frequency of left auricular thrombosis. This was associated with improvement of parameters of intraatrial hemodynamics and lowering of elevated blood D-dimer levels. Clinical-instrumental predictors of presence of left auricular thrombosis and its dynamics during therapy with acenocoumarol were also elucidated.

The aim of the study was to analyze the importance of the rapid assay for D-dimer in the diagnosis of venous thromboses (VT). The study accrued 82 patients. There were 57 (70%) men and 25 (30%) women aged 16 to 86 years. Fifty-three patients were suspected of deep venous thrombosis (DVT) and 29 of pulmonary thromboembolism (PTE). In 49 of the 82 patients, the use of USD, isotope phlebography, x-ray and ventilation-perfusion scintigraphy of the lungs made it possible to verify the diagnosis of VT. In one case, it was verified on autopsy. In 33 patients, the suspicions were rejected. The blood assay for D-dimer was performed using the kit Roche/Diagnostika Stago. The method is based on agglutination of latex particles covered by monoclonal antibodies to D-dimer. Among the 49 patients with a verified diagnosis of VT, D-dimer was positive in 44 (89.8%) and negative in 5 (11.4%) patients. In the group of the 33 patients, in whom the diagnosis of VT was rejected, D-dimer was negative in 26 (78.8%) and positive in 7 (21.8%) patients. Thus, the sensitivity of the assay for D-dimer constituted 89.8% and the specificity 78,8%. The high sensitivity of the assay provides an opportunity of using D-dimer measurement as a screening method in patients suspected of VT. Negative D-dimer is helpful in excluding VT. If D-dimer is positive, the diagnosis should be confirmed by other methods.

To analyze efficiency of semi-quantitative fast D-dimer test in diagnosis of deep vein thrombosis (DVT) and thromboembolism of pulmonary artery (TPA).The study enrolled 42 patients (26 males and 16 females) aged 25 to 86 years. 30 and 12 of them were suspected to have DVT and TPA, respectively. DVT was verified at ultrasound dopplerography and radionuclide phlebography in 16 of 30 suspects. TPA was verified by x-ray, perfusion scintigraphy of the lungs and at autopsy (one case) in 7 of 12 suspects. D-dimer levels in the blood were measured by latex parts agglutination reaction. The parts were covered with monoclonal antibodies to D-dimer. The reagents were provided by the kit Roche/Diagnostica Stago.The D-dimer test was positive in 20 of 23 DVT patients and negative in 3 cases (13%). Of 19 patients with rejected diagnosis of DVT/TPA the test was negative in 17(89.4%) and positive in 2 patients (10.6%). Thus, sensitivity and specificity of the D-dimer test was 87% and 89.4%, respectively.High sensitivity of the test allows to use it in screening for DVT/TPA. Negative D-dimer test rejects DVT, while positive test needs verification by other methods.