Intrinsic coagulation cascade factors and hemostatic markers of endothelial dysfunction in patients with peripheral artery disease

АРТЕРИОСКЛЕРОЗ ОБЛИТЕРИРУЮЩИЙВНУТРЕННИЙ КАСКАД КОАГУЛЯЦИИГЕМОСТАТИЧЕСКИЕ МАРКЕРЫДИСФУНКЦИЯ ЭНДОТЕЛИЯАЗОТА ОКСИДЫАЗОТА ОКИСЬАЗОТА (II) ОКСИДВИЛЛЕБРАНДА ФАКТОРСОСУДИСТЫЕ ХИРУРГИЧЕСКИЕ ОПЕРАЦИИЦель. Оценка активности факторов внутреннего каскада коагуляции и гемостатических маркеров дисфункции эндотелия у пациентов с облитерирующим атеросклерозом артерий нижних конечностей (ОААНК) до и после эндоваскулярных вмешательств. Материал и методы. В исследование было включено 80 пациентов с ОААНК IIБ-III стадии по А. В. Покровскому-Фонтейну. 40 пациентов с ОААНК подверглись эндоваскулярным вмешательствам на аорто-бедренно-подколенном сегменте (группа А), и 40 пациентов прошли консервативное лечение (группа В). Пациентам было проведено физикальное обследование, ультразвуковая допплерография (УЗДГ), дуплексное сканирование (УЗДС)/рентгеноконтрастная ангиография артерий нижних конечностей. Через 3 и 6 месяцев после проведенного лечения пациенты повторно прошли физикальное обследование, УЗДГ и УЗДС артерий нижних конечностей. При включении пациентов в исследование и через 3 месяца после операции были взяты образцы венозной крови для оценки активности факторов VIII, IХ, ХI, фактора фон Виллебранда (ФВ), оксида азота II (NO) и протеина С (ПрС). Результаты. У пациентов группы А до оперативного вмешательства средние значения активности VIII, IX, XI факторов и ФВ были повышены по сравнению с нормой. Через 3 месяца после операции наблюдался еще больший рост активности VIII, IX, XI факторов, сохранялся повышенный уровень ФВ при снижении показателей метаболитов NO. У пациентов группы В были повышены средние значения активности IX, XI факторов, ФВ при нормальном уровне метаболитов NO и ПрС. Заключение. Анализ исходного состояния системы гемостаза у пациентов с ОААНК позволяет сделать вывод о развитии гиперкоагуляционного состояния на фоне нормального антикоагуляционного потенциала. Оперативное вмешательство способствует еще большему сдвигу в сторону гиперкоагуляции и нарушению функционального состояния эндотелия.Objective. To assess the activity of intrinsic coagulation cascade factors of coagulation and hemostatic markers of endothelial dysfunction in patients with atherosclerotic peripheral artery disease (PAD) before and after endovascular treatment. Methods. The study included 80 patients with PAD in the stage IIB-III of the disease according to Pokrovsky-Fontaine classification. 40 patients with PAD underwent endovascular interventions on the femoropopliteal segment (group A) and 40 patients underwent the conservative treatment (group B). Patients underwent physical examination, ankle-brachial index measurement (ABI), duplex ultrasound (DUS) and digital substraction angiography. 3 and 6 months after treatment patients underwent the same procedures. At inclusion of patients in the study and 3 months after the surgery, peripheral venous blood samples were collected to assess the activity of VIII, IX, XI, von Willebrand factor (VWF), protein С (PrC) and metabolites of nitric oxide II (NO). Results. In patients of the group А mean values of activity VIII, IX, XI factors and VWF were increased in comparison with the norm before the surgery. After 3 months the results shown a greater increase in activity VIII, IX, XI factors, the elevated levels of VWF remained in the reduction of NO metabolites. In patients of the group B the mean activity values of IX, XI factors and VWF were increased with normal levels of NO metabolites and PrC. Conclusions. The analysis of the initial state of the hemostasis system in patients with atherosclerotic peripheral artery disease allows us to conclude that the hypercoagulable state develops against the background of a normal anticoagulation potential. Operative procedures provide a further shift towards a hypercoagulable state and impaired functional activity of endothelium

Coagulation Factor Activity and Hemostatic Markers of Endothelial Dysfunction in Patients with Peripheral Arterial Disease

Purpose: We aimed to evaluate the impact of intrinsic coagulation factors and hemostatic markers of endothelial dysfunction on complications in patients with atherosclerotic peripheral arterial disease (PAD). Materials and Methods : This prospective study enrolled 120 PAD patients at Fontaine stages 2b to 3 who underwent open surgical, endovascular, or conservative treatment. Coagulation factors (FVIII, FIX, and FXI) and endothelial hemostatic markers, including von Willebrand factor (vWF) activity and level, soluble endothelial protein C receptor, and plasminogen activator inhibitor-1 (PAI-1) levels, were assessed. Results : At 3 months after open bypass grafting, activity of FVIII significantly increased from a median of 175% to 233% (P<0.001). At 3 months after endovascular treatment, the activities of FVIII, FIX, and FXI significantly increased from medians of 157%, 180%, and 156% to 184%, 218%, and 181%, respectively (P<0.05). Six patients with increased FVIII activity developed bypass graft thrombosis. Four patients in the endovascular group and three patients in the conservative treatment group with increased activity of vWF developed myocardial infarction (P=0.049). The subjects who developed restenosis had increased vWF activity (P=0.023) and decreased nitric oxide metabolite levels (P=0.003). Three subjects who received conservative treatment and developed PAD progression at 12 months had increased PAI-1 activity (P=0.028). Conclusion : Patients with advanced PAD had a hypercoagulable status, and performance of open or endovascular revascularization was associated with further hypercoagulability. Increased activity of coagulation factors and altered levels of hemostatic markers of endothelial dysfunction were associated with PAD complications such as graft thrombosis, myocardial infarction, disease progression, and restenosis

Rivaroxaban with or without aspirin in stable cardiovascular disease

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events