KIDNEY ULTRASOUND PARAMETERS AND RENAL BLOOD BIOCHEMISTRY MARKERS IN POST-HEMORRHAGIC STROKE HYPERTENSIVE SURVIVORS

Introduction. Hemorrhagic stroke is a serious and devastating complication of arterial hypertension, which leads to increased mortality in survivors even after the early recovery period. Being other target organs for arterial hypertension, kidneys take part in blood pressure regulation. Investigation of their peculiarities in such patients may provide valuable data on possible reasons of poor long-term prognosis in this category of patients. The aim of the study: to compare kidney ultrasound parameters and renal blood biochemistry tests between the post-hemorrhagic stroke hypertensive subjects in a stable phase of recovery period and the patients with arterial hypertension who had no cerebrovascular and cardiovascular events. Materials and methods. There were 100 subjects enrolled into the study. They formed two investigatory groups: the main (n=64; age – 52,2±8,41 years, M±SD years) and the control (n=36; age – 51,8±5,92 years) one. Hypertensive patients of the main group developed hemorrhagic stroke – subarachnoid hemorrhage (SAH) (n=42) or intracerebral hemorrhage (ICH) (n=22) – ≥6 months prior to the examination conducted at this study. The control group consisted of patients with non-complicated arterial hypertension. In both groups of patients, the kidney ultrasound parameters and blood plasma urea, creatinine and uric acid concentration levels were determined. Estimated glomerular filtration rate (eGFR) was calculated. Results. The indices of kidney ultrasound parameters in the main group and the control group were the following ones, respectively: the pole-to-pole size of the right kidney was 9,96±1,05 and 11,63±1,26 cm, the same size of the left kidney – 10,39±0,93 and 11,95±1,23 cm, p<0,01 for both pairs. Among the biochemistry blood plasma indices, uric acid concentration reached significant difference as well – 411,21±60,36 and 360,91±75,3 µmol/L in the relevant groups, respectively (p=0,04). On the other hand, eGFR did not show the difference between the study groups. The main group was characterized by a higher prevalence of kidney stone formation – OR 5,00 (95% CI, 1,83-13,65). The statistically significant higher incidence rate of calculus development was identified in two subgroups of the main group as well: for SAH – OR 3,08 (95% CI, 1,05-9,02), for ICH – OR 13,33 (95% CI, 3,69-48,15). When comparing to the control group, kidney cyst identification rate in the SAH subgroup referred to OR 3,08 (95% CI, 1,05-9,02), while kidney pelvis/calyces enlargement incidence rate was higher in the ICH subgroup OR 9,17 (95% CI, 2,15-39,06). Conclusions. The obtained data indicate the smaller pole-to-pole dimension of both kidneys in hypertensive subjects who suffered hemorrhagic stroke, accompanying higher incidence rate of kidney calculus formation in view of the increased blood plasma uric acid concentration. The same is typical for the SAH individuals subgroup but with the addition of prevalence of kidney cysts incidence rate. As for the ICH subgroup, in addition to the main group findings, pelvis/calyces enlargement is observed more frequently when comparing to the hypertensive only subjects

Гіперкоагулолабільність у хворих із фібриляцією передсердь і супутнім ожирінням: шлях до геморагій чи тромбоемболій?

Despite the increased hypercoagulability of the blood plasma in patients with AF, the study of the processes of plasma hemostasis has still received insufficient attention, especially in patients with comorbid obesity or with excessive body weight.Purpose of the study. To establish the specific features of the effect of concomitant obesity on the indices of plasma hemostasis in patients with AF, on the basis of which to identify prognostically significant risk factors for adverse arrhythmia.Materials and methods. 75 patients with permanent AF were examined. For deducing prognostically significant risk factors, we conducted a retrospective analysis of the case histories of 421 inpatients.Results. The presence of concomitant obesity in patients with AF is accompanied by an acceleration of the prothrombinase-forming stage both in the internal and external hemocoagulation pathways. At the same time, the increase in procoagulant properties of blood is associated with a significant increase in fibrinogen and soluble fibrin-monomer complexes against the background of depletion of fibrinolytic and anticoagulant blood activity, which is a reflection of changes at the level of all links of hemocoagulation. Most diagnostically significant coagulation factors in the risk of thrombotic complications in patients with atrial fibrillation and concomitant obesity can be considered a measure of INR &lt;0.8 before prescribing warfarin, INR content in the range &lt;2.0 during the 5 days of warfarin, the level of AT III before treatment &lt;65 %, activity of XII-dependent fibrinolysis &gt;30 minutes. Prognostically significant risk factors for small bleeding in patients with AF and associated obesity when taking warfarin are a BMI&gt; 40kg/m2, level of AT III ≥40 % and ≥130 %, and in patients with AF and normal body weight, the amount of small bleeding increases if variability of INR beyond 2.0–3.0 and levels of AT III ≥130 %, as well as in the spring period of the year.Conclusions. Patients with AF are characterized by a moderate increase in the thrombogenic potential of the blood, which is accompanied by a significant inhibition of anticoagulant activity, while an increase in BMI leads to further deterioration of hemostasis equilibrium with an increase in procoagulant properties, depletion of fibrinolytic and anticoagulant blood activity.Несмотря на повышенную гиперкоагулолабильность плазмы крови у пациентов с ФП, изучению процессов плазменного гемостаза крови до сих пор уделялось недостаточное внимание, особенно у пациентов с коморбидным ОЖ или с избыточной массой тела. Цель работы – установить особенности влияния сопутствующего ожирения на показатели плазменного гемостаза у больных с ФП, на основе чего выделить прогностически значимые факторы риска неблагоприятного течения аритмии.Материалы и методы. Обследовано 75 пациентов с постоянной ФП. Для выведения прогностически значимых факторов риска нами был проведён ретроспективный анализ историй болезни 421 стационарного пациента.Результаты. Наличие сопутствующего ожирения у больных с ФП сопровождается ускорением этапа протромбиназообразования как по внутреннему, так и по внешнему пути гемокоагуляции. При этом усиление прокоагулянтных свойств крови ассоциируется с достоверным повышением содержания ФГ и РФМК на фоне истощения фибринолитической и антикоагулянтной активности крови, что является отражением изменений на уровне всех звеньев гемокоагуляции. Наиболее диагностически значимыми коагуляционными факторами риска развития тромботических осложнений у больных с ФП и сопутствующим ожирением можно считать показатель МНО &lt;0,8 перед назначением варфарина, содержание МНО в пределах &lt;2,0 на протяжении 5 суток применения варфарина, уровень АТ ІІІ перед началом лечения &lt;65 %, активность ХIIа-зависимого фибринолиза &gt;30 минут. Прогностически значимыми факторами риска возникновения малых кровотечений у пациентов с ФП и сопутствующим ожирением на фоне приёма варфарина является ИМТ ≥40кг / м2, уровень АТ ІІІ ≤40 % и ≥130 %, а у больных с ФП и нормальной массой тела количество малых кровотечений увеличивается при вариабельности МНО за пределами 2,0–3,0 и уровне АТ ІІІ ≥130 %, а также в весенний период года.Выводы. Для больных с ФП характерно умеренное повышение тромбогенного потенциала крови, которое сопровождается значительным угнетением антикоагулянтной её активности, при этом увеличение ИМТ приводит к дальнейшему ухудшению гемостазиологического равновесия с усилением прокоагулянтных свойств, истощением фибринолитической и антикоагулянтной активности крови.Незважаючи на високу гіперкоагулолабільність плазми крові у хворих із ФП, вивченню процесів плазмового гемостазу крові приділялась донедавна недостатня увага, особливо в пацієнтів із коморбідним ожирінням чи надмірною масою тіла.Мета роботи – встановити особливості впливу супутнього ожиріння на показники плазмового гемостазу у хворих із ФП, на підставі чого виділити прогностично значущі фактори ризику несприятливого перебігу аритмії.Матеріали та методи. Обстежили 75 пацієнтів із постійною ФП. Для виведення прогностично значущих факторів ризику виконали ретроспективний аналіз історій хвороб 421 стаціонарного пацієнта з ФП.Результати. Наявність супутнього ожиріння у хворих із ФП супроводжується прискоренням етапу протромбіназоутворення як за внутрішнім, так і за зовнішнім шляхом гемокоагуляції. При цьому посилення прокоагулянтних властивостей крові асоціюється із вірогідним підвищенням вмісту ФГ і РФМК на тлі виснаження фібринолітичної та антикоагулянтної активності крові, що є відбиттям змін на рівні всіх ланок гемокоагуляції. Найбільш діагностично значущими коагуляційними факторами ризику розвитку тромботичних ускладнень у хворих із ФП і супутнім ожирінням можна вважати показник МНВ &lt;0,8 перед призначенням варфарину, утримання МНВ у межах &lt;2,0 протягом 5 діб застосування варфарину, рівень АТ ІІІ перед початком лікування &lt;65 %, активність ХІІа-залежного фібринолізу &gt;30 хвилин. Прогностично значущими факторами ризику виникнення малих кровотеч у пацієнтів із ФП і супутнім ожирінням на тлі приймання варфарину є ІМТ ≥40 кг/м2, рівень АТ ІІІ ≤40 % та ≥130 %, натомість у хворих із ФП і нормальною масою тіла кількість малих кровотеч збільшується при варіабельності МНВ за межами 2,0–3,0 та рівні АТ ІІІ ≥130 %, а також у весняний період року.Висновки. Для хворих із ФП характерне помірне підвищення тромбогенного потенціалу крові, що супроводжується значним пригніченням антикоагулянтної її активності, при цьому збільшення ІМТ призводить до дальшого погіршення прокоагулянтних властивостей виснаженням фібринолітичної та антикоагулянтної активності крові

Hemostasiological Aspects of PCI: Periprocedural Changes in the Activity of the Platelet Link of Hemocoagulation on the Background of Prior Double Antiplatelet Therapy in Patients with Chronic Coronary Syndrome

The aim. To analyze changes in the activity of the platelet link of hemocoagulation in patients with chronic coronary syndrome before and after percutaneous coronary intervention (PCI) against the background of prior antiplatelet therapy. Materials and methods. We examined 67 patients (mean age 65.2±8.6 years) who were undergoing inpatient treatment at the National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine. Patients with different regimens of antiplatelet therapy were compared before and after PCI. At the time of hospitalization, patients were receiving both monotherapy and dual antiplatelet therapy (those with a history of myocardial infarction up to 12 months) in standard doses. The control group consisted of 25 people of similar age (62.7±6.5 years). The activity of platelet hemostasis was evaluated by the turbidimetric method and the light transmission fluctuation method. Statistical processing was carried out using the MedStat v.5.2 and Statistica 8.0 software. Results. Before PCI, dual antiplatelet therapy using aspirin and ticagrelor suppressed the activity of platelet hemostasis, compared to dual antiplatelet therapy with acetylsalicylic acid and clopidogrel. Patients receiving monotherapy did not achieve the desired effect. After PCI, the group of patients who took the combination of aspirin and ticagrelor responded better to the therapy than those who received aspirin and clopidogrel. Conclusions. The use of dual antiplatelet therapy with acetylsalicylic acid and ticagrelor reduced both spontaneous and induced aggregation

Hypercoagulability in patients with atrial fibrillation and associated obesity: a way to hemorrhage or thromboembolia?

Despite the increased hypercoagulability of the blood plasma in patients with AF, the study of the processes of plasma hemostasis has still received insufficient attention, especially in patients with comorbid obesity or with excessive body weight. Purpose of the study. To establish the specific features of the effect of concomitant obesity on the indices of plasma hemostasis in patients with AF, on the basis of which to identify prognostically significant risk factors for adverse arrhythmia. Materials and methods. 75 patients with permanent AF were examined. For deducing prognostically significant risk factors, we conducted a retrospective analysis of the case histories of 421 inpatients. Results. The presence of concomitant obesity in patients with AF is accompanied by an acceleration of the prothrombinase-forming stage both in the internal and external hemocoagulation pathways. At the same time, the increase in procoagulant properties of blood is associated with a significant increase in fibrinogen and soluble fibrin-monomer complexes against the background of depletion of fibrinolytic and anticoagulant blood activity, which is a reflection of changes at the level of all links of hemocoagulation. Most diagnostically significant coagulation factors in the risk of thrombotic complications in patients with atrial fibrillation and concomitant obesity can be considered a measure of INR 30 minutes. Prognostically significant risk factors for small bleeding in patients with AF and associated obesity when taking warfarin are a BMI> 40kg/m2, level of AT III ≥40 % and ≥130 %, and in patients with AF and normal body weight, the amount of small bleeding increases if variability of INR beyond 2.0–3.0 and levels of AT III ≥130 %, as well as in the spring period of the year. Conclusions. Patients with AF are characterized by a moderate increase in the thrombogenic potential of the blood, which is accompanied by a significant inhibition of anticoagulant activity, while an increase in BMI leads to further deterioration of hemostasis equilibrium with an increase in procoagulant properties, depletion of fibrinolytic and anticoagulant blood activity

Apixaban versus warfarin in patients with atrial fibrillation

BACKGROUND: Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. METHODS: In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. RESULTS: The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P = 0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P = 0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P = 0.42). CONCLUSIONS: In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. Copyright © 2011 Massachusetts Medical Society. All rights reserved

Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: A subgroup analysis of the ARISTOTLE trial

Background: In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. Methods: Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18 201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. Findings: Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with and 0·22 (-0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA. Interpretation: The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. Funding: Bristol-Myers Squibb and Pfizer. © 2012 Elsevier Ltd