Changes In Hemostasis Research Articles

Разработка и апробация нового метода определения параметров гемостаза у больных с психической патологией

Introduction: hemostasis is one of the most important protective systems of the organism, and its deviations from the norm can lead to fatal results. Changes in hemostasis are observed in many diseases, including mental pathology. In addition, parameters of this system may also change during antipsychotic therapy. Objective: Development and testing of a new method and device for estimating plasma hemostasis parameters in patients with mental pathologies in order to optimize treatment and eliminate fatal outcomes. Materials and methods: in the study we used frozen (-80 °C) platelet-free blood plasma (PFP) samples from patients with schizophrenia (16 patients), taken at admission to the clinic FSBSI «Mental Health Research Centre». Plasma coagulation of patients and healthy donors was assessed with the device of our design. Hemostasis assessment is based on the determination of the clot size in proportion to the brightness of the image, which changes as a result of clot formation and lysis. Results: optimal concentrations of coagulation and fibrinolysis activators, as well as concentrations of calcium ions were determined during the first stage of testing the method and device. The median values of all parameters of coagulation and fibrinolysis except «time before the formation of a clot» in patients upon admission to the clinic were reduced relative with combined plasma donors. The rates of clot formation and lysis in patients are significantly reduced at discharge compared with these parameters at admission. Consequently, these parameters can serve as an estimate of the change in the state of the coagulation and fibrinolysis systems during treatment. Conclusion: during approbation of the device and method in the process of coagulation and fibrinolysis research in patients with schizophrenia, lower levels of parameters were detected compared to donors, and a decrease in the activity of plasma coagulation and fibrinolysis during treatment with antipsychotics was shown.

Quantitative morphological characteristics of platelet hemostasis in patients with type 1 and 2 diabetes mellitus depending on the glomerular filtration rate.

Background. The use of only a complex of clinical and laboratory parameters characterizing the state of the kidneys and a lipid profile profile with anamnestic data to determine the initial manifestations of functional renal insufficiency is not sufficient. This necessitates the search for new, more informative markers for the risk of development and progression of diabetic nephropathy in type 1 diabetes mellitus patients, which may be endothelial dysfunction markers and morphological parameters of thrombocyte hemostasis. Objective. The purpose of the study is to analyze the quantitative parameters of platelet hemostasis in patients with diabetes mellitus type 1 and type 2, depending on the velocity of glomerular filtration rate. Methods. Transmission electron microscopy and phase contrast microscopy quantitatively assessed the state of platelet hemostasis in the blood of 66 patients with type 1 diabetes mellitus and 58 patients with type 2 diabetes mellitus, depending on the velocity of glomerular filtration rate. Results. Quantitative characterization of the morphological features of platelet hemostasis revealed early signs of damage to the platelet structure, which occur at normal levels of glomerular filtration rate in patients with diabetes mellitus type 1 and type 2. Increased degranulation of alpha-granules and the growth of circulating platelet aggregates in the setting of significant activation of thrombocytes in the hyaline type are the most sensitive signs of hemostasis disorder in patients without clinical signs of diabetic kidney disease. The degree of pathomorphological changes in platelet count in patients with type 2 diabetes mellitus is higher than that of type 1 diabetes mellitus. With the progression of diabetic nephropathy, there is a significant deepening of platelet hemostasis disorders with the involvement of ultrastructural lesions of erythrocytes and leukocytes, massive platelet degranulation, the formation of numerous complex platelets, consolidation of correlations between the greater part of morphological parameters characterizing the hemostatic profile in patients with diabetes mellitus 1 and 2 type. Conclusion. Morphological changes in platelet hemostasis in patients with diabetes mellitus occur to the clinical manifestations of diabetic kidney disease and clearly correlate with the profundity of diabetic nephropathy at the stages of its development.

Routine postprocedure ultrasound increases rate of detection of femoral arterial thrombosis in infants after cardiac catheterization.

To examine the effect of implementing postcatheterization ultrasound (US) on femoral arterial thrombosis detection rates and factors associated with thrombosis in infants. Although femoral arterial thrombosis is an uncommon complication of cardiac catheterization, it can cause limb threatening complications. Previous studies assessing the utility of postprocedure US to detect thrombosis in infants have utilized US as an adjunct to standard clinical detection methods, are small scale, or include small cohorts of infants within older populations. We reviewed institutional records of patients 0-12 months undergoing catheterization from 2007 to 2016. Demographics and procedural data were compared between the thrombosis and non-thrombosis group. Pre- and post-US groups were compared for detected thrombosis rate. Using univariate and multivariable analyses, we identified factors associated with thrombosis. In total, 270 patients underwent 509 catheterizations, with 40 (7.9%) documented thromboses. The rate of thrombus detection in patients younger than 6 months increased from 8.3% to 23.4% (P = 0.006) after implementing routine US. On multivariable analysis, lower weight (P < 0.001), larger arterial sheath size (P < 0.001), and longer procedure duration (P = 0.003) were independently associated with higher odds of thrombosis. Higher rates of femoral arterial thrombosis detection were observed since implementing an US screening program. Further studies are needed to evaluate age-related changes in hemostasis in this population and how advanced screening methods and anticoagulation protocols may help improve short-term and long-term sequelae of femoral arterial thrombosis.

Role of ADTRP (Androgen-Dependent Tissue Factor Pathway Inhibitor Regulating Protein) in Vascular Development and Function.

BackgroundThe physiological function of ADTRP (androgen‐dependent tissue factor pathway inhibitor regulating protein) is unknown. We previously identified ADTRP as coregulating with and supporting the anticoagulant activity of tissue factor pathway inhibitor in endothelial cells in vitro. Here, we studied the role of ADTRP in vivo, specifically related to vascular development, stability, and function.Methods and ResultsGenetic inhibition of Adtrp produced vascular malformations in the low‐pressure vasculature of zebrafish embryos and newborn mice: dilation/tortuosity, perivascular inflammation, extravascular proteolysis, increased permeability, and microhemorrhages, which produced partially penetrant lethality. Vascular leakiness correlated with decreased endothelial cell junction components VE‐cadherin and claudin‐5. Changes in hemostasis in young adults comprised modest decrease of tissue factor pathway inhibitor antigen and activity and increased tail bleeding time and volume. Cell‐based reporter assays revealed that ADTRP negatively regulates canonical Wnt signaling, affecting membrane events downstream of low‐density lipoprotein receptor‐related protein 6 (LRP6) and upstream of glycogen synthase kinase 3 beta. ADTRP deficiency increased aberrant/ectopic Wnt/β‐catenin signaling in vivo in newborn mice and zebrafish embryos, and upregulated matrix metallopeptidase (MMP)‐9 in endothelial cells and mast cells (MCs). Vascular lesions in newborn Adtrp −/− pups displayed accumulation of MCs, decreased extracellular matrix content, and deficient perivascular cell coverage. Wnt‐pathway inhibition reversed the increased mmp9 in zebrafish embryos, demonstrating that mmp9 expression induced by Adtrp deficiency was downstream of canonical Wnt signaling.ConclusionsOur studies demonstrate that ADTRP plays a major role in vascular development and function, most likely through expression in endothelial cells and/or perivascular cells of Wnt‐regulated genes that control vascular stability and integrity.

Platelet Function Changes in a Time-Dependent Manner Following Traumatic Brain Injury in a Murine Model.

Traumatic brain injury (TBI) results in systemic changes in coagulation and inflammation that contribute to post-traumatic morbidity and mortality. The potential interaction of platelets and pro-inflammatory cytokines in the modulation of coagulation, microthrombosis, and venous thromboembolic events after moderate TBI has not been determined. Using a murine model, we hypothesized that the degree of platelet-induced coagulation varies depending on the platelet aggregation agonist platelet-induced coagulation changes in a time-dependent manner following TBI, and changes in platelet-induced coagulation are mirrored by changes in the levels of circulating pro-inflammatory cytokines. An established weight-drop model was used to induce TBI in anesthetized mice. Blood samples were collected at intervals after injury for measurements of platelet count, serum fibrinogen, pro-inflammatory cytokines, and determination of soluble P-selectin levels. Thromboelastometry was used to evaluate changes in hemostasis. Platelet function was determined using whole blood impedance aggregometry. Ten minutes following TBI, adenosine diphosphate-induced platelet aggregation decreased as measured by platelet aggregometry. Despite no changes in platelet counts and serum fibrinogen, platelet aggregation, pro-inflammatory cytokines, and soluble P-selectin were increased at 6 h after TBI. Rotation thromboelastometry demonstrated increased maximal clot firmness at 6 h. Platelet function and coagulability returned to baseline levels 24 h following head injury. Our data demonstrate that after TBI, acute platelet dysfunction occurs followed by rebound platelet hyperaggregation. Alterations in post-TBI platelet aggregation are reflected in whole blood thromboelastometry and are temporally associated with the systemic pro-inflammatory response.

PO360 Haemostasis Changes and Endothel Activation During Pulmonary Vein Isolation

PO360 Haemostasis Changes and Endothel Activation During Pulmonary Vein Isolation

Detection of biomarkers using a novel proximity extension assay in patients with ST-elevation myocardial infarction

BackgroundST-elevation myocardial infarction (STEMI) involves inflammation, activation of platelets, coagulation and changes in fibrinolysis as well as remodelling of myocardial tissue after STEMI. Recently, new proximity extension assays including panels of biomarkers for cardiovascular disease have been developed. This study investigates a wide range of cardiovascular protein biomarkers in the acute phase of STEMI compared with the stable phase three months after STEMI.We hypothesized that major changes in inflammation, haemostasis, tissue remodelling, and proteolysis are prevalent. Materials and methodsThis was a prospective, observational study including 48 STEMI patients (mean age 60 ± 12 years, 79% men) treated with primary percutaneous coronary intervention (PPCI). Blood samples were obtained immediately prior to PPCI and again three months later. Levels of 92 biomarkers reflecting inflammation, immune response, cell adhesion, haemostasis, fibrinolysis, tissue remodelling, and proteolysis were assessed using a proximity extension assay (Olink® CARDIOVASCULAR III). ResultsWhen comparing the acute phase of STEMI with the stable phase three months later, a total of 29 biomarkers differed significantly after Bonferroni correction (p < 0.0005). In the acute phase of STEMI, we found an overall increase of biomarkers reflecting immune and inflammatory response, cell adhesion, and haemostasis. Biomarkers reflecting tissue remodelling and proteolysis were increased at three months follow-up compared with the acute phase. Out of the 29 biomarkers, six biomarkers did not confirm our predefined hypotheses. ConclusionsUsing a novel proximity extension assay technique, we detected changes in several biomarkers when comparing the acute phase with three months follow-up in patients with STEMI. These biomarkers may play important roles in the pathogenesis of STEMI.

Changes in coagulation hemostasis when using colloidal solutions during off-pump coronary artery bypass grafting surgery

The results of the use of colloidal and crystalloid solutions during surgical intervention of patients with coronary heart disease are presented. The effect of colloidal solutions on the coagulation hemostasis system and the associated perioperative complications were studied. The study included 60 patients operated in the NIST named after O.O. Shalimov on coronary heart disease who underwent off-pump coronary bypass grafting surgery: 40 patients (in the intraoperative period solutions of hydroxyethyl starch 130/0.4 were used (20 patients) and 4% gelatin (20 patients) were used in the intraoperative period); the comparison group included 20 patients (only crystalloid solutions were used in the intraoperative period). The results of general and biochemical analysis of blood, electrolyte, acid-base and gas composition of blood were analyzed, prothrombin time was determined, prothrombin index, international normalized ratio, activated partial thromboplastin time, thromboelastometry. The statistical analysis of the material was carried out using standard methods using the application package “MS Excel” and “StatPlus 2007 Professional”. Evaluated the average, standard errors, the authenticity of the differences. To estimate the intergroup difference, the parametric t-criterion of the Student was used, while the links between the indicators were determined - a correlation analysis by Pierson. The results obtained showed a negative effect on the coagulation hemostasis system of colloidal solutions (changes in the thromboelastometry, prothrombin time and index) and an increase in the frequency of postoperative complications (blood loss, the need for blood transfusion, prolonged stay in the intensive care unit and hospital). The results of the study provide a perspective in the further study of the effect of colloidal solutions on coagulation hemostasis during other surgical interventions (thoracic, abdominal, etc.), as well as the use of the thromboelastometry method in clinical practice for early diagnosis of coagulation hemostasis disorders.

The relationship between brain microbleeds and homeostatic markers in the treatment of ischemic stroke

ABSTRACTObjectives: There is no definitive data regarding the usefulness of Brain microbleeds (BMBs) as an imaging marker with homeostatic markers to predict intracerebral hemorrhage (ICH) and ischemic stroke risk to personalize decisions on anticoagulation in AF. In this study, we prospectively evaluated clinical, radiological homeostatic biomarkers and their association with stroke outcomes in 73 AF-related ischemic stroke patients.Methods: All BMBs were measured manually on Susceptibility-Weighted Imaging (SWI). The levels of NT-pro-BNP, hs-CRP, FVII, FVIII and vWF were studied as homeostatic markers. For all patients, we calculated CHADS2, CHA2DS2-VASc, HAS-BLED scores and modified Rankin Scale (mRS) scores. Functional independence and good clinical outcome were defined as a mRS score of 0-2.Results: The mean age of the study population was 69.74 ± 9.79 years, and 36 patients were female. The leading vascular risk factor was hypertension (61%). BMBs were determined in 20 patients (27.4%) on SWI, 12 patients had less than five lesions. Presence of BMBs lesions on SWI was significantly associated with age and hypertension (p = .020) and congestive heart failure (p = .011). The median CHA2DS2-VASc score in patients was 4.96 ± 1.54. CHA2DS2-VASc score (p = .042), CHADS2 score (p = .037) and HAS- BLED score (p = .033) were significantly related with the presence of BMBs in the study patients. Among homeostatic markers, the levels of NT-pro-BNP, hs-CRP, and vWF were significantly associated with the presence of microbleeds (p = .013, p = .029, p = .020, respectively).Conclusion: Pathogenesis of AF is involved abnormal changes of hemostasis, endothelial dysfunction, antithrombotic state and inflammation. The homeostatic markers, which play role in these pathways, and the presence of BMBs could use to form a prognostic clinic assessment tool to predict bleeding risk.

STATE OF HEMOSTASIS AND LIPID EXCHANGE IN SUBSTITUTE HORMONOTHERAPY IN WOMEN IN THE MENOPAUSAL PERIOD

The survey studied the effect of transient transdermal application of estrogen (estradiol, at a dose of 50 micrograms per day) on changes in blood lipid levels and indicators of the hemostatic system.The aim of the study. was to evaluate changes in blood lipid levels and hemostasis in transient transdermal estrogen administration.Materials and methods of research: 36 women aged 49 to 59 years were under observation. The average duration of menopause was 49.0 ± 5 months. At the beginning of the study, the patients had different vegetovascular disorders, which are typical for the menopause period. The condition of all women at the beginning of the study was characterized as stable.Results of the research and their discussion: As a result of the study, it was noted that the use of estrogen preparations led to an increase in the serum estradiol level after the fourth week of treatment, and a decrease in the total cholesterol and low-density lipoprotein (LDL) cholesterol was noted. The average level of indicators of the hemostasis system tended to decrease, reaching a maximum value at the end of therapy.Conclusions: It is necessary to use HRT to menopausal women with several symptoms of the perimenopausal syndrome, but with the caution, in the connection with the fact that along with favorable changes in blood lipid levels, improvement in the patients well-being, a negative effect of therapy is observed – the development of relative tryglycerideemia, a decrease in the level of antithrombin III, a risk of proliferative processes of the endometrium.

Acute myocardial infarction in elderly and senile patients: Hemocoagulative infringements

Aim: To establish the pathophysiological mechanisms of an unfavorable acute myocardial infarction (AMI) on basis of study of the platelet hemostasis changes in elderly and senile patients in order to optimize diagnostics.

Characteristic of the hemostasis indices in chronic venous insufficiency in stage of decompensation

Objective. To compare the hemostasis indices in patients, suffering chronic venous insufficiency (CHVI) in decompensation stage, owing or not the thrombotic complications.&#x0D; Маterials and methods. The indices of hemostasis were studied up in 47 patients, suffering CHVI in decompensation stage, in whom the blood was obtained from central and regional blood flow. To Group I 27 patients were included, suffering CHVI in decompensation stage and complicated by an acute varicothrombophlebitis. To Group II (control) were included 20 patients, suffering CHVI in a decompensation stage without thrombotic complications.&#x0D; Results. The indices of hemostasis of the regional blood flow of Group I and Group II differ significantly more, than the hemostasis indices of the central blood flow.&#x0D; Conclusion. The changes in hemostasis in patients, suffering an acute varicothrombophlebitis, are predominantly of a local character.

Relationship Between Haemostasis Parameters and Anxiety Under Examination Stress: A Pilot Study.

This work aims to clarify how blood coagulation parameters reflect mild stress response in males and females. Healthy student volunteers of both sexes were used in this pilot study. A new global sensitive assay of haemostasis, spatial thrombodynamics, along with conventional coagulometry approach were used to evaluate of blood coagulation parameters. Psychodiagnostics scales (according to Spielberger and Taylor) are employed to evaluate anxiety as stress-induced response. We have selected exam stress, which despite being a mild stressor may nevertheless cause somatic disorders. We provide the first evidence of a statistically significant increase in initial clot growth velocity in women, but not men, in response to exam stress. The exam situation produces higher situational anxiety in female volunteers, and so they express remarkable stress-induced haemostatic responses, including plasma- and platelet-based changes. In contrast, male volunteers do not express pronounced stress-induced changes in haemostasis, and only display a decrease in plateletcrit value and an increase in prothrombin time. Mild form of stress (exam) induces changes in some blood coagulation parameters. A statistically significant remarkable increase in Vinit value and some other plasma- and platelet-based parameters has been seen in female students (but not male ones) under exam stress.

The posttraumatic activation of CD4+ T regulatory cells is modulated by TNFR2- and TLR4-dependent pathways, but not by IL-10

Platelets modulate the immune system following injury by interacting with CD4+ T regulatory cells (CD4+ Tregs). The underlying mechanisms remain unsolved. We hypothesize paracrine interactions via Tumor necrosis factor-alpha (TNFα)-, Toll like receptor-4 (TLR4)-, and Interleukin-10 (IL-10).In the murine burn injury model, CD4+ Treg activation pathways were selectively addressed using TNFR2-, TLR4- and IL-10-deficient mice. The CD4+ Treg signalling molecule PKC-θ was analyzed using phospho-flow cytometry to detect rapid cell activation. Thromboelastometry (ROTEM®) was used to assess platelet activation.Injury induced significant early activation of CD4+ Tregs, disruption of TNFR2 and TLR4 activation pathways resulted in lower activity. The disruption of IL-10 crosstalk had no significant impact. Selective disruption of paracrine interactions is associated with changes in posttraumatic hemostasis parameters.TNFR2- and TLR4-dependent pathways modulate the activation of CD4+ Tregs following trauma. In contrast, we did not observe a role of IL-10 in the posttraumatic activation of CD4+ Tregs. One sentence summaryTLR4- and TNFR2-dependent mechanisms, but not IL-10-dependent pathways, modulate the anti-inflammatory response of CD4+ Tregs following trauma.

Оцінка показників коагулограми у пацієнтів з тромбозом системи нижньої порожнистої вени

Мета. Оцінити зміни показників коагулограми у пацієнтів з тромбозом глибоких вен (ГВ) системи нижньої порожнистої вени (НПВ) залежно від виду лікування.&#x0D; Матеріали і методи. Проведена кількісна оцінка показників коагулограми у 615 пацієнтів із тромбозом у системі НПВ. Залежно від методу лікування хворі розподілені на дві групи: 1-ша – 380 (61,8%) хворих, яким провели хірургічне лікування з наступним призначенням антикоагулянтної терапії; 2-га – 235 (38,2%) хворих, яким призначали лише антикоагулянтну терапію.&#x0D; Результати. Оцінка більшості показників коагулограми показала більш виражену гіпокоагуляцію у пацієнтів 1-ї групи порівняно з 2-ю групою: рівень D-димеру був нижче на 14,1%, середня концентрація тромбокриту (СКТ) - на 7,8%, протромбіновий індекс (ПІ) - на 7,1%, міжнародне нормалізоване співвідношення (МНС) - на 3,8%, рівень гематокриту - на 2,4%, кількість тромбоцитів - на 1,9%. У пацієнтів 1-ї групи спостерігали більш виражене подовження активованого часткового тромбопластинового часу (АЧТЧ), активованого часу рекальцифікації (АЧР) та протромбінового часу (ПЧ) порівняно з пацієнтами 2-ї групи: на 37,9, 10,6 та 4,8% відповідно. Водночас рівень фібриногену у 1-й групі був на 9,1% вище порівняно з 2-ю групою.&#x0D; Висновки. Гіпокоагуляційні зміни гемостазу у пацієнтів, яким застосували хірургічне лікування тромбозу ГВ системи НПВ, порівняно з пацієнтами, яким призначали лише антикоагулянтну терапію, дають підстави припустити, що механічне видалення тромботичних мас сприяє більш швидкій нормалізації показників гемостазу.

Thromboelastography in wild Florida manatees (Trichechus manatus latirostris).

Thromboelastography (TEG) provides a comprehensive evaluation of blood clot formation. This test can be used to identify abnormalities in coagulation by assessing multiple aspects of the clotting cascade, including the speed of clot initiation and formation, clot strength, and ultimately fibrinolysis. Thromboembolic disease has been hypothesized to play a role in the pathophysiology of cold stress syndrome (CSS), an important cause of mortality in the threatened Florida manatee (Trichechus manatus latirostris). The objective of this study was to establish thromboelastography RIs using the TEG 5000 with citrated whole blood samples and kaolin activation in wild, healthy manatees. In December 2014 and January 2015, 29 wild manatees (17 male and 12 female) were blood sampled as part of the annual wild manatee health assessments organized by United States Geological Survey (USGS). TEG was performed using citrated kaolin-activated samples. The samples were obtained from manatees caught in Crystal River, Citrus County, and used to identify the mean±SD of normal TEG parameters: R=reaction time 2.1minutes (0.8), K=clot formation time 0.8min (0), α angle=83.1° (2), MA=maximum amplitude 75mm (7.6), and LY30=clot lysis 0.41% (0.68). No significant differences were found between manatee size, sex, or time between sampling and running the test. Manatee TEG parameters demonstrate a relatively hypercoagulable condition when compared to other mammals. This information will facilitate detection of changes in hemostasis during injury and disease and provide a valuable reference range.

Viscoelastic Testing in Liver Disease

Long thought to be hypocoagulable, new evidence suggests cirrhosis patients have “rebalanced” coagulation in the setting of decreased synthesis of both pro- and anti-coagulant factors. Traditional testing like PT/INR reflects only the decreased synthesis of pro-coagulant factors and thus does not correspond to bleeding or clotting risk in this population. In this review, we discuss the use of viscoelastic testing (VET), an assay of global hemostasis in cirrhosis patients. We describe the technique and interpretation of commercially available VET and assess the application of VET in both transplant and non-transplant cirrhosis populations. VET largely correlates well with traditional testing including platelet count and fibrinogen level, however, is potentially less accurate in patients with low fibrinogen levels. VET may be useful in identifying patients at higher risk of hypercoagulable complications post-transplant and reflects changes in hemostasis in decompensated patients. While VET has been associated with decreased transfusion support in multiple studies, the lack of bleeding in patients who avoided prophylactic transfusion suggests a “rescue” rather than prophylactic approach to transfusion may be ideal and further studies with a “rescue” arm are needed. Additional prospective studies of VET should include clinically relevant endpoints of bleeding and thrombosis.

СПОНТАННЫЕ СГУСТКИ НА ФОНЕ ПРИЁМА ДАБИГАТРАНА ЭТЕКСИЛАТА КАК ФАКТОР ГИПЕРКОАГУЛЯЦИИ ПРИ ЭНДОПРОТЕЗИРОВАНИИ ТАЗОБЕДРЕННОГО СУСТАВА

Цель исследования: сравнительная оценка показателей гемостаза, полученных различными методами, у пациентов, которым выполнялось первичное эндопротезирование тазобедренного сустава (ТБС) и проводилась профилактика тромбоэмболических осложнений (ТЭО) дабигатраном этексилатом Материалы и методы. Обследовано 27 пациентов (17 женщин и 11 мужчин) с коксартрозом III стадии, которым выполнялось первичное эндопротезирование ТБС. Для профилактики ТЭО все пациенты получали дабигатрана этексилат, длительность профилактики составила 35 дней. Оценку состояния системы гемостаза проводили до операции, в первые и пятые сутки после операции клоттинговыми методами, методами тромбоэластографии и тромбодинамики. Результаты. Показана взаимосвязь наличия спонтанных сгустков, выявленных тестом тромбодинамика, с признаками высокой гемокоагуляционной активности. Сравнительная оценка показателей системы гемостаза, определенных различными методами в плазме и цельной крови, показала, что 1) стандартные тесты коагулограммы отражают только отдельные изменения системы гемостаза и 2) образование спонтанных сгустков в тесте ТД может с большой вероятностью указывать на состояние гиперкоагуляции и быть основой для стратификации пациентов по наличию факторов риска гиперкоагуляции. Использование фиксированной профилактической дозы дабигатрана этексилата не обеспечило адекватной коррекции гиперкоагуляционного состояния у пациентов, перенесших тотальное эндопротезирование ТБС. Заключение. Данное исследование может служить отправной точкой для персонификации дозирования дабигатрана этексилата в целях профилактики ТЭО у пациентов, имеющих исходно высокий гемокоагуляционный потенциал. The aim was to compare hemostasis parameters obtained by different methods, in patients who underwent primary total hip arthroplasty (TBS) with postoperative antithrombotic prophylaxis using dabigatran etexilate. Materials and methods. We examined 27 patients (17 women and 11 men) with coxarthrosis (stage III) after primary hip joint endoprosthetics. For prophylaxis of thromboembolic complications all patients received dabigatran etexilate, the duration of prophylaxis was 35 days. We assessed hemostasis state before, on the first and fifth days after operation using clotting tests, thromboelastography and thrombodynamics. Results. Results shows the relationship of spontaneous clots in cromodinamica with signs of high clotting activity. Comparative evaluation of hemostasis parameters in the plasma and in whole blood showed that 1) conventional coagulation tests specifies only isolated changes in hemostasis, and 2) the appearance of spontaneous clots are likely to indicate a hypercoagulability and to be the basis to stratify patients according to hypercoagulation risk. Fixed doses of dabigatran etexilate did not provide proof prevention in patients undergoing total joint hip replacement. Conclusion. This study can be seems a starting point to personalize the dabigatran etexilate dosing in such patients with initially high coagulation potential.

Dynamics of the Parameters of Platelet Hemostasis in Patients with Ischemic Stroke after Systemic Thrombolytic Therapy

Were examined 89 patients with ischemic stroke (IS) (mean age 58.54 (55.05, 64.73)), 42 of them with systemic thrombolytic therapy (TLT) (mean age 64.26 )60.58; 68,06)) and 47 patients with IS without TLT (54,52 (47,48, 60,83)). In the subgroup of moderate severity (from 7 to 14 points in NIHSS) included 13 patients after TLT, of severe severity (more than 15 points for NIHSS) included 29 patients after TLT. The determination of platelet hemostasis was carried out by the method of Born and O'Brien with the determination of aggregation, sizes of platelet aggregates for adrenaline, аdenosine diphosphate (ADP), ristomycin, spontaneous aggregation and fibrinogen concentrations on days 1, 7 and 14. Clinical evaluation of the severity of the condition was carried out according to the NIHSS scale. Specific features of changes in platelet hemostasis in inducers (adrenaline, ristomycin, ADP) in patients with IS after TLT at 1, 7 and 14 days in comparison with the indices of patients without TLT and their relationship with the dynamics of neurologic deficit, which allow to clarify the features of the vascular flow process, its forecast.

Features of platelet hemostasis changes and antiplatlet treatment sensitivity in patients with stable forms of ischemic heart disease

Aim: To study and to estimate the aggregation activity of platelets in patients with stable forms of IHD, taking into account their sensitivity to the antiplatelet treatment and influence of ITGA2 polymorphism.Materials and methods: there were examined 45 patients, who were on treatment in the Clinic “PheopHanya” (city Kyiv) and in Kyiv clinical hospital of railway transport № 2: 22 women and 23 men (mean age – 66,8±9,5 years). The study included patients with stable forms of IHD (stable effort angina of ІІ-ІІІ FC). All patients received the antiplatelet treatment with acetylsalicylic acid (48,9%), clopidrogel (37,8%) or their combination (13,3%).The functional activity of platelets was studied on the laser aggregometer Biola Aggregation Analyser. The reaction to the antiplatelet treatment was confirmed using Aggredyne-test. C807T polymorphism of ITGA2 was determined by the method of polymerase chain reaction (PCR).Based on the results of aggregation activity, sensitivity to the antiplatelet treatment, patients were distributed in two groups: І group – persons with the different degree of resistance to antiplatelet drugs (21 patients), ІІ group – sensitive to the treatment (24 persons). Polymorphism of ITGA2 and features of platelets functional activity depending on genotype were analyzed in each group.Results: Among all inductors of aggregation, only the reaction to arachidonic acid (AA) was less than control values (by 12,7%, р&lt;0,05). The degree of the spontaneous and adenosine dyphosphate (ADP)-induced aggregation didn’t differ from the norm, collagen-induced one was 1,21 times higher than the control. The quantity of patients, insufficiently sensitive to the treatment was 46,7 % (21persons), according to the data of Aggredyne-test, 24 persons had an adequate response to the treatment. At the analysis of ITGA2 polymorphism Т/Т genotype prevailed in patients “non-respondents”, in ‘respondents” - С/С genotype. Т-allele presence among respondents was 90,5% persons, so the probability of its influence on sensitivity to the antiplatelet treatment was rather high.Conclusions: The decrease of sensitivity to antiplatelet drugs, connected with ITGA 2 polymorphism was observed in 46,7% of patients with stable IHD: resistance to the antiplatelet therapy is associated with Т/Т genotype of ITGA 2, presence of Т-allele in the genotype of patients-“non-respondents” was observed in 90,5% of persons, С/С genotype prevails at a positive response to the treatment