Soluble Fibrin Monomer Complexes Research Articles

Prediction of survival in non-Hodgkin lymphoma based on markers of systemic inflammation, anemia, hypercoagulability, dyslipidemia, and Eastern Cooperative Oncology Group performance status

AbstractBackgroundThe International Prognostic Index and its modifications are used to estimate prognosis in non-Hodgkin lymphoma. However, the outcome is often different in patients with similar index scores.AimThe aim of this study was to elaborate a prognostic model for patients with mature B-cell non-Hodgkin lymphoma using a combination of predictive markers.Material and methodsThe study included 45 patients with mature B-cell non-Hodgkin lymphoma. Before the administration of treatment, clinical and laboratory parameters were measured. After the 35-month follow-up period, overall survival was studied in relation to the data obtained at initial examination.ResultsWe revealed nine adverse predictive markers for overall survival of enrolled patients: Eastern Cooperative Oncology Group (ECOG) performance status >1; erythrocyte sedimentation rate >30 mm/h; levels of hemoglobin <120 g/L, fibrinogen ≥6 g/L, interleukin-6 ≥2 pg/mL, tumor necrosis factor ≥1.45 pg/mL, soluble fibrin monomer complexes >4 mg/dL, high-density lipoprotein cholesterol <1.03 mmol/L in men, and <1.29 mmol/L in women; and short activated partial thromboplastin time. A prognostic model for the estimation of the risk of death within the ensuing 1.5–2 years in patients with non-Hodgkin lymphoma was constructed.ConclusionMarkers of inflammation, anemia, hypercoagulability, dyslipidemia, and poor ECOG status are associated with worse survival in patients with mature B-cell non-Hodgkin lymphoma.

Комплексное лечение пациентов с хронической ишемией, угрожающей потерей конечности: все ли возможности антикоагулянтной терапии нами используются?

Background: medical correction of the hemostatic system is one of the most important directions for complex treatment of obliterating diseases of lower limbs arteries (ODLLA), including cases of chronic limb-threatening ischaemia (CLTI).Aim: to evaluate the efficacy and safety of the sulodexide use in patients with ODLLA when conducting a comprehensive treatment of CLTI.Patients and Methods: 520 patients underwent two-center prospective study, 318 of whom (211 — with signs of ODLLA, 107 — without signs of CLTI) underwent revascularization interventions, whereas, 202 patients with CLTI received multicomponent complex conservative treatment. In addition to standard treatment, 30 patients who underwent surgery interventions and the group of 50 patients receiving conservative treatment received sulodexide orally in 2 capsules bis in day (1000 LE/day). The severity of the pain syndrome, the distance of pain-free walking, some laboratory indicators of hemostatic system, as well as the presence of adverse events and complications were evaluated before and after treatment. Results: in operated patients with both CLTI and without it, regardless of the sulodexide use, there was a significant decrease in the severity of pain syndrome and an increase in the distance of pain-free walking. Sulodexide use was accompanied by reduced fibrinogen, D-dimer, soluble fibrin monomer complexes (SFMC) and plasminogen activator inhibitor (PAI-1) in the subgroup of patients with CLTI, and indicators of fibrinogen and PAI-1 in the subgroup of patients without CLTI (p<0.05). In non-operated patients with CLTI, sulodexide use was accompanied by a decrease in pain syndrome and indicators of fibrinogen, D-dimer, SFMC, and PAI-1 (p<0.05). However, it was less significant after performed revascularization. There were no adverse events or complications associated with the sulodexide use.Conclusions: improvement of clinical and laboratory parameters was mainly determined by the efficacy of performed limb revascularization. In the complex treatment of patients with ODLLA, the sulodexide use was safe and effective, which was manifested by a decrease in the pain severity, an increase in the distance of pain-free walking and normalization of some coagulogram indicators.KEYWORDS: chronic limb-threatening ischaemia, critical limb ischemia, obliterating diseases of lower limb arteries, complex treatment, sulodexide.FOR CITATION: Katelnitsky I.I., Darvin V.V., Zorkin A.A. Comprehensive treatment of patients with chronic limb-threatening ischaemia: are we using all the possibilities of anticoagulant therapy? Russian Medical Inquiry. 2020;4(7):445–451. DOI: 10.32364/2587-6821-2020-4-7-445-451.

Crosstalk between inflammation and coagulation in pancreatitis-induced renal injury in experimental and clinic acute pancreatitis

Background: The pathogenesis of organ failure in AP is complicated. Proteases, inflammatory cells and its mediators which secreted from pancreas into blood circulation and impairment of blood coagulation, microcirculations are explaining as the main contributed factors for organ failure in AP. Acute renal failure is a serious early complication in patients with AP significantly increases mortality rates. Materials and Methods: For the experiment were used 42 Wistar albino rats. We examined 98 patients with moderately severe AP, and 57 patients with severe AP. Disorders of kidney function were in 48 patients. We determined the creatinine level, indicators of hemostasis and inflammation. Results: In the kidneys characteristic of experimental acute necrotizing pancreatitis were: edema, inflammatory infiltration of the parenchyma, parenchymal congestion and dilation of capillaries, tubular necrosis. The concentration of creatinine in serum is increase at 86.86%. It was noticed that the level of creatinine significantly directly correlated with the concentration of MPO and activity of iNOS in the tissue of pancreatic, amylase in serum blood, reverse with the concentration of H2S in serum. Renal failure in rats was accompanied by a hypercoagulation. Analysis of the relationship of inflammation and hemostasis in patients with acute pancreatitis and renal dysfunction is accompanied by decreased of activated partial thrombolastin time, increased of thrombin time, fibrinogen concentration, D-dimers level, and level of soluble fibrin-monomer complexes, lack of activity of antithrombin III, increased synthesis of C-reactive protein, excessive production of proinflammatory cytokines IL-2, IL-6, and TNF-α. Was shown a direct correlation between severity of renal failure (SOFA score) and concentrations of IL-6, CRP, D-dimers, soluble fibrin-monomer complexes, and duration of thrombin time. Conclusion: The mechanism of the acute renal injury following severe necrotizing pancreatitis is complicated. The inflammatory cascades and hypercoagulative state are initiated this pathological process.

THROMBOSE-PREVENTIVE INFLUENCE OF QUERCETIN IN RATS ON THE HYPER-COAGULATION DIET

Relevance. Hyper-coagulation processes increase the risk of coronary heart disease.
 Objective of the study was to study the effect of quercetin on the hemostatic system when using hyper-coagulation diet in rats.
 Materials and methods. The study included 17 male rats weighing 240-270 g. The rats of the control group (n = 6) were fed with conventional compound feed; Group I rats (n = 5) - mixed feed; and group II rats (n = 6) mixed with meat and quercetin (1.33 g/l). After 21 days, sterile blood was collected. The Amellung Coagulometer KS 4A studied the external and internal blood coagulation pathways, the activity of their own anticoagulant and fibrinolytic blood systems. The data obtained were statistically processed using Excel 2010 and Statistica v.10 (StatSoft, USA).
 Results. In rats of group 1, the external pathway of blood coagulation underwent the most significant changes, as indicated by an almost four-fold acceleration of prothrombin time and a decrease in the international normalized ratio. From the side of the internal pathway, the greatest changes were recorded in the last phase of clot formation: thrombin time decreased by 39.8% with an almost constant rate of activated partial thromboplastin time (APTT), which confirmed the activation of the fibrin formation phase. In addition, the content of soluble fibrin-monomer complexes (RFMC) increased 1.7 times and the fibrinogen decreased. At the same time, depletion of the anticoagulant potential of the blood was observed (a 42.2% decrease in the activity of the protein C system with a tendency to a decrease in antithrombin III (AT III). The fibrinolytic system was significantly suppressed, as indicated by more than three times inhibition of XII-dependent fibrinolysis. In animals Group 2 compared with the indicator in group 1, APTT was 2 times longer; the concentration of RFMC was also doubled, fibrinolysis was activated by 25%.
 Conclusion: The use of quercetin bioflavonoids in animals with simulated coronary heart disease slows down blood coagulation and potentiates the anticoagulant system, including due to a 40% increase in AT III activity, can be considered as a thrombosis-preventive effect

Time-dependent systemic hemostatic effects of fibrin monomer in controlled liver injury in the experiment

Aim. To evaluate the hemostatic effect of fibrin monomer after its intravenous administration at different time periods in experimental trauma. Methods. In the experiments, in a placebo-controlled study, hemostatic and hemostasiological effects of systemic use of fibrin monomer were studied at different time periods after its administration (in 5 min, 1 h and 3 h) in 97 male rabbits of the Chinchilla breed in the controlled liver injury model. Results. A pronounced hemostatic effect was demonstrated for fibrin monomer used at a dose of 0.25 mg/kg demonstrated by a 6.3-fold decrease of blood loss volume (% of circulating blood volume) compared to placebo on the background of the intravenous preventive fibrin monomer administration 1 hour prior to controlled liver injury. Fibrin monomer administration at a stated dose was not accompanied by significant changes in haemocoagulative parameters including measurement of platelet count, activated partial thromboplastin time, prothrombin time, thrombin time, echitox time, fibrinogen concentration, level of soluble fibrin monomer complexes, D-dimer content, and antithrombin III activity. The effect of fibrin monomer is probably realized through some effectors, the nature of which has not yet been studied. The obtained results allow choosing the optimal interval between intravenous administrations of fibrin monomer and controlled liver injury for further study of the mechanisms of its hemostatic action. Conclusion. Fibrin monomer in small doses (0.25 mg/kg) is able to exert a pronounced hemostatic effect with its systemic administration 1 hour prior to the injury without significant changes in haemocoagulative parameters.

Hemostasis parameters in patients after coronary artery bypass surgery for stable angina

The objective of research is to assess the significance of hemostatic profile in the postoperative period after coronary artery bypass surgery for predicting the one-year functioning of the grafts. Materials and methods. 46 men, who had coronary artery bypass surgery (CABS) for stable angina, were examined. 23 of them had 2 type diabetes mellitus (DM2), 23 of them did not have diabetes mellitus. All patients underwent fibrinogen, soluble fibrin monomer complex, D-dimer, induced platelet aggregation and lupus anticoagulant blood tests on the 14th day after surgery. The patients had coronary and bypass graft angiography for the assessment of graft patency a year after surgery. Results. During the postoperative period, there were no statistically significant differences between patients with DM2 and patients without DM2 in the results of the above hemostatic profile tests (p value for the Mann-Whitney test is >0.05). Lupus anticoagulant was detected in 9 patients with DM2 and in 12 patients without DM2 (p value for Fisher’s exact test is 0.554). 10 patients with DM2 and 6 patients without DM2 had graft occlusions a year after surgery; the differences for this sign were not statistically significant (p value for Fisher’s exact test is 0.18). Fibrinogen, soluble fibrin-monomer complex, D-dimer, and induced platelet aggregation tests did not demonstrate prognostic significance in relation to graft occlusions in both groups of patients (p for χ 2 in the logistic regression model is >0.05). The factors associated with higher risk of graft occlusion in patients with DM2 were high ratio between screening and confirmatory test for the detection of lupus anticoagulant (odds ratio 2.27; 95% -confidence interval 1.119-1.238; p <0.05). Conclusion. After coronary bypass surgery, the one-year risk of graft thrombosis is higher in patients with DM2 and high positive LA activity.

Сlinical and prognostic value of total fibrinogen level and its role in heart disorders on the background of different gallbladder conditions

Total fibrinogen (TF) is in the focus of attention of scientists and doctors since Hippocrates’ time. Fibrous component of thrombus was for the first revealed in the end of XVII century. Term “fibrin” was introduced in 1801, “fibrinogen” – in 1847, despite the latter was discovered in 1859. Nowadays TF is considered to be not only criterion of inflammation activity, but also a marker of cardiovascular risk. The aim of this study: estimation of the modern condition of the problem of TF analysis and usage according to literature data and own clinical results. Material and methods. We organized a literature search in PubMed database and domestic sources. Fibrinogen concentration (gravimetric method of R.A. Rutberg), level of soluble fibrin-monomer complex (SFMC) (Tehnologiya-Standart, Russia) and D-dimers (TECHNOZYM D-dimer ELISA, Austria) were estimated in 489 patients with ischemic heart disease (IHD), hemorrhagic vasculitis (HV), and rheumatic fever (RF) in patients with different gallbladder (GB) conditions. Results were analyzed with the help of variational statistics. Data was considered significant if p<0.05. Results. Fibrinogen is a hexamer glycoprotein of plasma, which acts as a key regulator of inflammation, plays an important role in hemostasis, wound healing and angiogenesis. In patients with IHD, HV and RF its amount varied from 2.20 to 8.05 g/L. The highest levels were revealed in case of unstable angina pectoris (4.23±0.16 g/L, р<0.05 in comparison with groups of HV and RF, where we observed the minimal concentration: 3.31±0.14 g/L). Conclusions. TF level was dependent on GB condition: minimal levels were observed in case of intact GB (3.67 g/L, the lowest ones – in patients with RF: 3.02±0.20 g/L), and maximal – in case of bent GB body (4.04 g/L). Correlational analysis revealed the association of TF with parameters of inflammation, lipid metabolism, liver function, left ventricle hypertrophy, which can be a sign of TF prognostic. In case of GB changes we observed also increase of SFMC and D-dimers. This fact proves the activation of thromboproduction and is a unfavourable prognostic value factor of vascular events.

Тест генерации тромбина в оценке адаптационных возможностей системы гемокоагуляции у пациентов с дегенеративно-дистрофическими заболеваниями суставов

Введение. Поиски методов оценки функционального состояния системы гемокоагуляции у пациентов, которые ожидают выполнения эндопротезирования крупных суставов нижних конечностей, обоснованы высокой частотой встречаемости у них тромбоэмболических осложнений. Цель исследования: изучение теста генерации тромбина (ТГТ) с позиции оценки адаптационных возможностей системы гемокоагуляции у больных с дегенеративнодистрофическими заболеваниями крупных суставов нижних конечностей. Материалы и методы. Обследован 141 больной с дегенеративнодистрофическими поражениями тазобедренных и коленных суставов (35 мужчин, 106 женщин), средний возраст 62,6 9,9 лет. Контрольную группу составили 30 условно здоровых доноров, средний возраст 49,7 6,5 лет. Исследовали коагуляционные свой ства крови рутинными методами и регистрировали кривую процесса тромбинообразования в ТГТ, анализируя параметры: tlag латентное время тромбинообразования, ttpeak время достижения максимума тромбина, peak максимальное количество тромбина, VI индекс скорости тромбинообразования, AUC площадь под кривой. Больные были разделены на 2 группы в зависимости от характера изменения временных параметров ТГТ в ответ на инициацию тромбиногенеза активаторами с концентрацией тканевого фактора 2 пмоль/мл (активатор RB) и 5 пмоль/мл (активатор RClow). Результаты. В 1й группе значения параметров tlag и ttpeak в ответ на действие активатора RClow были меньше, чем на действие активатора RB, реакцию системы гемокоагуляции расценивали как адекватную. Во 2й группе значения tlag и ttpeak при использовании активатора RClow превышали величины аналогичных параметров при инициации тромбообразования активатором RB, а корреляционный анализ отразил ослабление связей между параметрами ТГТ, что свидетельствовало об адаптационной перестройке системы на фоне высокого тромбогенного потенциала и повышенном риске развития гемокоагуляционных осложнений у больных 2й группы. Заключение. ТГТ с использованием активаторов RB и RClow ерспективный инструмент выявления больных с высоким риском развития послеоперационных гемокоагуляционных осложнений. Introduction. The search of methods for assessing of hemocoagulation functional state in patients that are waiting endoprosthesis replacement of large joints of lower extremities is justified by the high incidence of thromboembolic complications. Aim: to study thrombin generation assay (TGA) for assessment of hemocoagulation adaptive potential in patients with degenerativedystrophic diseases of the large joints of lower extremities. Materials and methods. We examined 141 patients with degenerativedystrophic lesions of hip and knee joints (35 men, 106 women), average age was 62.6 9.9 years. Control group consisted of 30 relatively healthy donors, average age was 49.7 6.5 years. We investigated blood coagulation properties by routine methods and recorded the curve of thrombin formation by TGA. We analyzed next parameters: tlag is the latent time of thrombin formation, ttpeak is the time to reach the maximum of thrombin, peak is the maximum amount of thrombin, VI is the index of thrombin formation speed, AUC is the area under the curve. Patients were divided into 2 groups according TGA parameters in response to thrombinogenesis initiation by activators with different tissue factor concentrations 2 pmol/ml (RB activator) and 5 pmol/ml (RClow activator). Results. In the 1st group, tlag and ttpeak values in TGA with RClow activator were less than with RB activator, the hemocoagulation response was regarded as adequate. In the 2nd group, tlag and ttpeak values with RClow activator were higher than with RB activator and correlation analysis revealed the weakening of the relationships between TGA parameters. This indicated about system adaptation at a time of high thrombogenic potential and about increased risk of developing hemocoagulation complications in patients of the 2nd group. Conclusion. TGA with RB and RClow activators is a promising tool for identifying patients with a high risk of postoperative hemocoagulation complications.

Prothrombotic states in women with infertility and psychosomatic disorders

Failures of in vitro fertilization (IVF) may be associated with prothrombotic states, the circulation of antiphospholipid antibodies (APA). 93 women with infertility were screened: the first group 32 women without severe psychosomatic disorders; the second group 61 women with psychosomatic disorders. The control group consisted of 30 fertile women. We carried out measurements in the blood serum of the level of AFA to membrane phospholipids (phosphatidylethanolamine, phosphatidylserine, cardiolipinum), antibodies to β2-glycoprotein (Iβ2-GPI), hemostasis (platelet count, ADP-induced platelet aggregation index, fibrinogen concentration, prothrombin index, activated partial thromboplastin time APTT, test for soluble fibrin-monomeric complexes, D-dimer), homocysteine, molecular genetic study of polymorphous variants for β-fibrinogen (C148T, 455GA) genes. The frequency of significant AFA titres in the group of women without psychosomatic disorders was 18.9%, and in women with psychosomatic disorders 44.3%, the rate of β2-GPI 9.6% in the first group versus 24.5% in the second group. Only in 11.5% of women in the second group elevated levels of APA were associated with β2-GPI and/or one or more clinical criteria for antiphospholipid syndrome (APS). In patients with infertility and psychosomatic disorders, we found increased platelet aggregation in the context of relative thrombocytopenia, higher fibrinogen levels, soluble fibrin-monomeric complexes, and prolonged APTT with elevated D-dimer levels. Some patients had hyperhomocysteinemia. In patients with psychosomatic disorders, the frequency of the minor alleles of the locus C148T and 455GA of the β-fibrinogen gene was greater than 40% (25–30% in first group). We distinguished factors that adversely affect the efficiency of IVF in the patients with psychosomatic disorders: elevation of APA; reduction in the number of thrombocites; growth of the ADP-induced aggregation index; extension of APTT; increase of fibrinogen, D-dimer; homocysteine; the presence of the minor allele of the T polymorphic locus C148T of the β-fibrinogen gene. The presence of prothrombotic states associated with APS should be taken into account when preparing for IVF and the appropriate correction should be made for them.

457Efficacy and safety of uninterrupted periprocedural edoxaban in patients undergoing catheter ablation for atrial fibrillation: Prospective KYU-RABLE study

Abstract Background/Introduction Catheter ablation (CA) has been established as a first-line therapy in the treatment of non-valvular atrial fibrillation (NVAF), and uninterrupted direct oral anticoagulants (DOACs) have become mainstream for the management of periprocedural thromboembolic events. Since 2014, edoxaban has been used for anticoagulation therapy for AF in Japan. However, evidence for uninterrupted use of edoxaban during the periprocedural period of CA in NVAF patients is limited. Purpose KYU-RABLE is a prospective, multicenter, single-arm interventional study, conducted in 23 institutions in Japan to evaluate the efficacy and safety of uninterrupted periprocedural oral edoxaban in patients undergoing CA. The plasma concentration of edoxaban and its relation with plasma coagulative biomarker levels during the periprocedural period were also evaluated. Methods A total of 537 Japanese NVAF patients were enrolled in Japan from December 2017 to September 2018. Edoxaban 60mg (30 mg in patients indicated for dose adjustment) was administered once daily in the morning for at least 4 weeks before CA and continued for at least 4 weeks after CA. On the day of CA, edoxaban was administered immediately after confirmation of hemostat. The primary endpoint was the composite incidence of thromboembolism and major bleeding events during 4 weeks from the procedural day. Plasma concentration of edoxaban and plasma levels of coagulative biomarkers including D-dimer, soluble fibrin monomer complex (SFMC) and prothrombin fragment 1+2 (F1+2) were also measured. Results Among the total 513 patients who underwent CA, 75.2% had radiofrequency CA and 23.0% had cryoballoon CA. The majority of CA patients (65%) received edoxaban 60mg/day, while others (35%) received 30mg/day. As for the primary endpoint, one major bleeding (cardiac tamponade) event was observed and no thromboembolism occurred. Clinically relevant non-major bleeding events occurred in six patients (1.2%), the most were puncture site hemorrhage. The plasma concentration of edoxaban at CA was dependent upon the duration from last administration of edoxaban before CA. However, plasma levels of coagulative biomarkers (D-dimer, SFMC, F1+2) were maintained within appropriate range during the periprocedural period, irrespective of the edoxaban concentration. We also report changes of plasma levels of coagulative biomarkers in sub group analyses by CHADS2 scores and types of AF. Conclusion The KYU-RABLE study demonstrated the first evidence of the efficacy and safety of uninterrupted periprocedural edoxaban administered once daily on the morning for NVAF patients underwent CA. Edoxaban treatment was associated with a low risk of periprocedural bleeding and thromboembolic complications. Furthermore, these low event risks were considered to be associated with the maintained plasma level of coagulative biomarkers, regardless of the change in edoxaban plasma concentration. Acknowledgement/Funding Daiichi Sankyo Co. Ltd.

Evaluation of the effectiveness of chronocorrection of hemocoagulation and microcirculation by angioprotectors and antiplatelet agents of diabetic microangiopathy

The efficacies of four protocols for treating patients with insulin-dependent diabetes mellitus (IDDM) and microangiopathies of the I and II degree are compared: traditional therapy with pro dectin (250 mg) and trental (100 mg) 3 times daily (17 patients), prodectin (250 mg) and aspirin (125 mg) 3 times a day (16 patients), chronotherapy with prodectin in a dose of 250 mg and trental in a dose of 100 mg once a day (17 patients), and prodectin (250 mg) and aspirin (125 mg) once a day 1.5-2 h before the acrophase of the circadian rhythm of blood coagulation, microcirculation, and peripheral hemodynamics parameters (16 patients). Before and 15-17 days after treatment, blood coagulation values were studied by the autocoagulation and hemolysate aggregation tests, measurements of blood fibrinogen, antithrombin III, soluble fibrin monomer complexes, and fibrinolytic activity of the blood; microcirculation was assessed by biomicroscopy of the eye conjunctiva, and peripheral hemodynamics by the radioactive xenome method and rheova- sography of the shin. The studies demonstrated a higher efficacy of chronotherapy in comparison with traditional prodectin in combination with trental and aspirin.

ПАТОГЕНЕТИЧНА ЗНАЧИМІСТЬ ВИЯВЛЕННЯ ПОРУШЕНЬ В СИСТЕМІ ГЕМОСТАЗУ ДЛЯ ДІАГНОСТИКИ ТА ПРОФІЛАКТИКИ ТРОМБОТИЧНИХ УСКЛАДНЕНЬУ ЖІНОК З АНТЕНАТАЛЬНОЮ ЗАГИБЕЛЛЮ ПЛОДА

Стаття узагальнює аргументи та контраргументи в межахнаукової дискусії з питання діагностики та профілактики порушень в системігемостазу у жінок з антенатальною загибеллю плода. Основною метою даногодослідження є вивчення зміни системи гемостазу у вагітних з антенатальноюзагибеллю плода, а саме оцінка особливостей прокоагулянтної, антикоагулянтноїта фібринолітичної ланок системи гемостазу у жінок з антенатальною загибеллюплода. Систематизація літературних джерел та підходів до проблемигемостазіологічних порушень при антенатальній загибелі плода дає змогупідтвердити важливість даного питання, обґрунтовано оцінювати ризики під часвагітності у кожної конкретної жінки та, в першу чергу проводити профілактикувиникнення даного ускладнення. В даній статті надані результатиретроспективного дослідження індивідуальних карт вагітних та історій пологіввагітних з антенатальною загибеллю плода та фізіологічною вагітністю в період з2016 – 2018 роки. Актуальність дослідження даної патології полягає у тому, щокожна пʼята жінка репродуктивного віку стикається з такою проблемою, якпeринатальні втрати. У структурі перинатальних втрат особливе місце посідаєантенатальна загибель плода, що може призводити до розвитку синдрому втратиплода, ДВЗ-синдрому, інфекційних ускладнень у матері та непліддя чисубфертильності у майбутньому, що вцілому негативно впливає на репродуктивнийпотенціал нації. В процесі роботи нами оцінювались такі показниками коагулограмияк: протромбіновий індекс, тромбіновий час, активований парціальний тромбіновийчас, розчинні фібрин мономерні комплекси, фібриноген плазми, антитромбін ІІІ тапротеїн С.Встановлено, що для вагітних з антенатальною загибеллю плода характернимє підвищення згортаючої активності крові на фоні пригнічення антикоагулянтноїта фібринолітичної ланок гемостазу. Визначення активності антитромбіну ІІІінформує про стан антикоагуляційної системи організму та надає можливістькоригувати лікування антикоагулянтними препаратами прямої дії. Показникикоагулограми не можуть повністю відобразити стан гемостазу під час вагітності,тому пошук нових методів ранньої діагностики дисбалансу в системі гемостазу під час вагітності залишається актуальним і на даному етапі. Дані дослідженняможуть бути корисними акушерам-гінекологам, особливо в жіночій консультаціїдля формування групи ризику вагітних та проведення профілактичних заходів зметою попередження антенатальної загибелі плода.

Elaboration of New Medical Technology for Predicting the Risk of Ischemic Heart Disease in the Workers of the Coal Industry

Background. Ischemic heart disease is the leading cause of death in the majority of developed countries, including Russia. It determines the importance of elaboration of individual risk prediction of ischemic heart disease for primary prevention.Aim: to develop a strategy for predicting the ischemic heart disease in coal industry workers.Materials and methods. Ischemic heart disease incidence and its risk factors were studied in 196 coalmine workers (sinkers, stope miners). Rose Questionnaire, daily ECG monitoring and bicycle ergometry were used to detect angina. The indices of lipid metabolism, hemostatic system, the level of homocysteine, uric acid, C-reactive protein, constitutional-morphological type by Rees – Eysenck, genetic markers of blood groups of AB0, P and MN systems were studied.When elaborating the prognostic system, we used the Bayes method. A prognostic coefficient was calculated for each factor. Prediction of ischemic heart disease was carried out according to the sum of prognostic coefficients.Results. Ischemic heart disease was detected in 18 (9.2 %) miners. According to the above mentioned indices, a medical technology was elaborated to predict the ischemic heart disease, based on the determination of the most significant risk markers: age, work experience in harmful working conditions, type A behavior, arterial hypertension, fasting hyperglycemia, metabolic syndrome, hypercholesterolemia, decrease in the level of high density lipoprotein cholesterol, increase in the value of low density lipoprotein cholesterol, hypertriglyceridemia, hyperhomocysteinemia, hyperfibrinogenemia, increase in the level of soluble fibrin monomer complexes and C-reactive protein, abdominal obesity, hypersthenic constitutional-morphological type by Rees – Eysenck, genetic markers of blood groups of AB0, P and MN systems.Conclusion. Based on the most significant markers, a personalized strategy for ischemic heart disease prediction in miners was elaborated, which allowed timely undertaking therapeutic and preventive measures.

Efficacy and Safety of Enoxaparin for Prophylaxis of Postoperative Venous Thromboembolism After Esophagectomy: A Single-center Prospective Randomized Controlled Phase II Study

This study aimed to assess whether low-molecular-weight heparin (LMWH) is effective and safe in preventing postoperative venous thromboembolism (VTE) in patients undergoing esophageal cancer surgery. In this single-institution, prospective, randomized trial, 73 patients with esophageal cancer undergoing esophagectomy were randomly divided into the enoxaparin group (E group) and intermittent pneumatic compression group (I group). The primary endpoint was efficacy of enoxaparin, and secondary endpoints were evidence of bleeding and serum anti-Xa activity in the E group. The E group comprised 42 patients and the I group comprised 31 patients. Deep vein thrombosis was observed in 0 (0%) patients in the E group and 7 (22.6%) patients in the I group (p=0.002). Soluble fibrin monomer complex was significantly lower in the E versus I group on day 8 (p<0.001). D-dimer was significantly lower in the E versus I group on days 2, 8, and 15 (p=0.008, p<0.001, p<0.001, respectively). VTE was significantly reduced by using enoxaparin.

Disturbances of the ultrastructure of endotheliocytes of sinusoid hemocapillaries of the liver and the hemostasis system in the acute period of cranial injury

Purpose of the study : the role of endothelial cells of the sinusoidal capillaries of the liver in the pathogenesis of the vascular-platelet and coagulation units of the hemostasis system to assess the acute period of traumatic brain injury. Materials and methods . Work is a clinical experimental study. TBI was simulated in animals and the number of blood thrombocytes was determined at 1, 3, 7, 12 days after the alteration. Also on the 3 rd , 7 th and 12 th day after the application of TBI, structural changes in sinusoidal hemocapillaries (SH) were studied in ultrathin sections of the liver. The study of patients was conducted at the Semashko Hospital. Hemostasis systems were evaluated in patients by the indicators: activated partial thromboplastin time, prothrombin and thrombin time, prothrombin index, fibrinogen, antithrombin III, soluble fibrin-monomer complexes, plasma fibrinolytic activity, platelet count in 1-e (on admission) and 3, 7 and 10 days of treating patients. Results . The results of electron microscopic examination of the liver SH and intravascular changes revealed that pronounced damage to endotheliocytes and microcirculation disorders were determined in animals on the 3 rd day of the post-traumatic period. These changes were aggravated on the 7 th day after the injury. Partial restoration of blood flow and endothelium with the preservation of areas of its swelling and edema occurred 12 days after TBI. The number of platelets significantly decreased with a maximum change in the index by day 7 and recovered to the values of intact rats on the 12 th day after TBI. The number of platelets decreased and coagulation hemostasis increased in patients with severe concurrent TBI on the 3 rd and 7 th day after injury compared to the reference intervals of the studied hemostasis parameters. Conclusion . In this way, a combination of non-specific systemic disorders of the structural and functional integrity of the vascular endothelium and activation of the blood coagulation system is observed in the acute period of severe TBI, which dictates the need for targeted prevention and correction of the above disorders in the complex treatment of patients.

Влияние хлорида никеля на показатели гемокоагуляции и липопероксидации у крыс в эксперименте

Цель исследования - изучить состояние системы гемостаза при хронической интоксикации хлоридом никеля, исследовать взаимосвязь показателей гемокоагуляции с процессами липопероксидации у крыс в эксперименте. Методика. Опыты проводили на крысах-самцах Вистар (n=50, 230-250 г). Раствор NiCl2 (5 мг/кг) вводили внутрижелудочно ежедневно в течение 2 нед, 1 и 2 мес. По завершении эксперимента исследовали состояние тромбоцитарного и коагуляционного звеньев гемостаза, антикоагулянтную и фибринолитическую активность крови, а также определяли активность процессов перекисного окисления липидов и антиоксидантных ферментов. Результаты. Установлено, что через 2 нед и 1 мес интоксикации у крыс отмечались гиперкоагуляционные изменения показателей свертывающей системы крови: повышение агрегационной активности тромбоцитов, увеличение концентрации фибриногена, снижение активированного частичного тромбопластинового времени (АЧТВ) и протромбинового времени. В этот период регистрировалось увеличение антитромбиновой и фибринолитической активности крови. Через 2 мес наблюдалось подавление активности клеточного звена гемостаза - тромбоцитопения, ослабление степени АДФ-индуцируемой агрегации тромбоцитов. Выявлялась тенденция к уменьшению концентрации фибриногена. На фоне снижения АЧТВ и тромбинового времени отмечалось увеличение протромбинового времени. В то же время регистрировалось угнетение противосвертывающего звена системы гемостаза (снижалась активность антитромбина III), наблюдалось истощение резервных возможностей фибринолитического звена (замедление фXIIа-зависимого эуглобулинового лизиса) и увеличение содержания растворимых фибрин мономерных комплексов, что свидетельствует о наличии тромбинемии. Через 2 нед, один и два месяца интоксикации у животных выявлялись корреляционные связи между основными показателями системы гемостаза и активностью процессов перекисного окисления липидов и антиоксидантных ферментов. Заключение. Полученные данные подтверждают наличие взаимосвязи активности процессов липопероксидации и системы гемостаза, в том числе при хронической никелевой интоксикации. Результаты исследования позволяют рекомендовать применение антиоксидантов для разработки способов коррекции гемостатических сдвигов при воздействии на организм тяжелых металлов. The aim. To study the state of the hemostasis system in chronic nickel intoxication and to investigate the relationship between hemocoagulation indices and lipoperoxidation processes in rats. Methods. Experiments were carried out on male Wistar rats (n=50, 230-250 g). A solution of nickel chloride (5 mg/kg) was administered daily intragastrically for two weeks, one and two months. At the end of the experiments, indices of platelet and coagulation hemostasis systems, anticoagulant and fibrinolytic activity of blood plasma, and activities of lipid peroxidation and antioxidant enzymes were studied. Results. Hypercoagulative changes in indices of the coagulation system were observed in rats after two weeks and one month of intoxication, including increased platelet aggregation and fibrinogen concentration and shortened activated partial thromboplastin time and prothrombin time. During the same period, increased antithrombin and fibrinolytic activities were observed. The depressed activity of the cellular component of hemostasis evident as thrombocytopenia and impaired ADP-induced platelet aggregation was detected after two months of intoxication. A tendency to decrease in fibrinogen concentration was observed. The shortened activated partial thromboplastin time and thrombin time were associated with prolonged prothrombin time. At the same time, inhibition of the anticoagulant component of hemostasis (decreased antithrombin III activity), exhaustion of the fibrinolysis system reserve (delayed fXIIa-dependent euglobulin lysis), and a significant increase in soluble fibrin monomeric complexes indicative of thrombinemia were observed. After two weeks, one and two months of nickel intoxication, a correlation was found between the major indices of the hemostasis system and the activities of lipid peroxidation and antioxidant enzymes. Conclusion. The study confirmed a relationship between the lipid peroxidation activity and the hemostasis system, specifically in chronic nickel intoxication. This result allows to recommend the use of antioxidants in developing methods for correction of hemostatic induced affected by heavy metals.

THE ROLE OF ENDOTHELIAL DYSFUNCTION AS A PART OF SYSTEMIC INFLAMMATORY RESPONSE IN PATHOGENESIS OF AGGRESSIVE AND INDOLENT NON-HODGKIN’S LYMPHOMAS

Objective. To study of manifestation of angiogenic and hemostatic forms of endothelial dysfunction and systemic inflammatory response in patients with non-Hodgkin’s lymphomas at the onset of disease. Material and methods. A total of 99 patients were enrolled in this study, including 55 patients with aggressive variants and 44 patients with indolent variants. The average age was 60.71±10.63 years. The serum level of vascular endothelial growth factor (VEGF) was measured as a marker of angiogenic form of endothelial dysfunction, the serum levels of thrombomodulin, D-dimers, soluble fibrin-monomer complex (SFMC) and level of Willebrand factor activity were used for evaluation of hemostatic form of endothelial dysfunction. To assess the degree of systemic inflammation response the serum levels of proinflammatory cytokines – TNF-α, IL-1β, IL-6 were measured, as well as serum level of acute phase proteins – C-reactive protein (CRP), fibrinogen. The serum level of IL-4 was used to evaluate antinflammation resistance. Results and discussion. Proinflammatory cytokine (TNF-α, IL-1β and IL-6) content was higher in both studied groups compare to the control group. Serum concentration of anti-inflammatory cytokine IL-4 in studied groups did not differ from the level in the controls group. CRP and fibrinogen serum content was increased only in group of patients with aggressive variants. There was a significant correlation between the level of CRP and proinflammatory cytokines in aggressive lymphoma group. Serum content of VEGF, thrombomodulin, D-dimers, SFMC and Willebrand factor activity were increased in both studied group in comparison with the control group. Concentration of thrombomodulin, D-dimers, SFMC and Willebrand factor activity was higher in patients with aggressive than in patients with indolent lymphomas. Conclusion. The signs of angiogenic and hemostatic forms of endothelial dysfunction in patients with aggressive and indolent variants of non-Hodgkin’s lymphoma were detected, as well as manifestation of systemic inflammatory response and attenuation of anti-inflammatory resistance with development of cytokines imbalance with proinflammatory cytokines predominance. The manifestations of systemic inflammatory response and hemostatic type of endothelial dysfunction with activation of coagulation were displayed more prominently in the aggressive lymphoma group.

Стан системи гемостазу за трансмісивної венеричної саркоми собак

Стан системи гемостазу за трансмісивної венеричної саркоми собак

РОЛЬ ЛЕГКИХ В ПОДДЕРЖАНИИ БАЛАНСА СИСТЕМЫ ГЕМОСТАЗА НА ФОНЕ ХРОНИЧЕСКОГО ВОЗДЕЙСТВИЯ ВОЗДУШНЫХ ПОЛЛЮТАНТОВ

The aim of the study is to determine the nature of the consequences of non-respiratory lung function disorders and their influence on the hemostatic system in chronic inhalation of industrial hydrogen sulfide gas (HS). There were studied the parameters of hemostasis system (the number and function of platelet, total clotting time, level of soluble fibrin-monomer complex and D-dimer, speed of XIIa-dependent euglobulin lysis, the activity of Willebrand factor and factors VIII, protein C and inhibitor of tissue plasminogen activator-1 (TPA-1), the content of antithrombin III and plasminogen) in 146 white laboratory male rats taking into account the artery-venous difference. Blood collection was carried out from the abdominal aorta (pars abdominalis aortae) ("after the lungs") and from the posterior vena cava (vena cava caudalis) ("to the lungs", that excludes the influence of the liver). The rats were divided into 9 groups: four groups were experimental, which were exposed to HS for one month (20 animals), two months (20 animals), three months (19 animals) and four months (19 animals). HS was fed into chambers at a concentration of 70±2.34 mg/m3 by static method (once). Inhalation of rats with gas lasted for 4 hours a day, 5 days a week. The control groups were rats placed in cells with a normal air composition in a similar mode for a period of one, two, three and four months (12 individuals each). The reference parameters of the hemostatic system were determined before the experiment in a group of 20 rats. It was found that the artery-venous difference in the indicators of soluble fibrin-monomer complex (p&lt;0.05), the content of antithrombin III (p&lt;0.05), the activity of protein C (p&lt;0.01) is more pronounced in the groups of the 1st month of exposure to HS. Increased activity of platelets (p&lt;0.05), of Willebrand factor (p&lt;0.05) and TPA-1 (p&lt;0.001), as well as slowing of fibrinolysis (p&lt;0.05) indicates the damage to the endothelium of pulmonary capillaries by the 4th month of HS inhalation and the decrease of ability of the lungs to regulate hemostasiological balance.

Prothrombotic states as risk factor of in vitro fertilization failures in women with infertility and psychosomatic disorders.

Failures of in vitro fertilization (IVF) may be associated with prothrombotic states, the circulation of antiphospholipid antibodies (APA). 93 women with infertility were screened: 1 group - 32 women without severe psychosomatic disorders; 2 group - 61 women with psychosomatic disorders. The control group consisted of 30 fertile women. The level of AFA to membrane phospholipids (phosphatidylethanolamine, phosphatidylserine, cardiolipinum), antibodies to β2-glycoprotein (β2-GPI), hemostasis (platelet count, ADP-induced platelet aggregation index, fibrinogen concentration, prothrombin index, activated partial thromboplastin time - APTT, test for soluble fibrin-monomeric complexes, D-dimer), homocysteine in the blood serum was defined. The frequency of significant AFA titres in the group of women without psychosomatic disorders was 18.9%, and if they were present - 44.3%, the rate of β2-GPI 9.6% versus 24.5%, respectively. Only in 11.5% of women in 2 groups, elevated levels of APA were associated with β2-GPI and/or one or more clinical criteria for antiphospholipid syndrome (APS). In patients with infertility and psychosomatic disorders, increased platelet aggregation in the context of relative thrombocytopenia, higher fibrinogen levels, soluble fibrin-monomeric complexes, and prolonged APTT with elevated D-dimer levels was revealed. Some patients have hyperhomocysteinemia. Factors that adversely affect the efficiency of IVF in the patients with psychosomatic disorders were noted: elevation of APA; reduction in the number of platelets; growth of the ADP-induced aggregation index; extension of APTT; increase of fibrinogen, D-dimer; homocysteine. The presence of prothrombotic states associated with APS should be taken into account when preparing for IVF and perform their appropriate correction.