COVID-19 vaccine-induced immune thrombotic thrombocytopenia

The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) stimulated the development of highly effective vaccines that were produced with unprecedented speed with the use of new technologies. All the newly developed vaccines are highly effective with minimal adverse effects. Clinical introduction of the AstraZeneca Covid-19 vaccine has raised public alarm regarding the rare, but serious thrombotic events, known as vaccine-induced immune thrombotic thrombocytopenia (VITT). VITT is characterized clinical and laboratory syndromes like: venous (acute cerebral sinus venous thrombosis and abdominal vein thrombosis) or arterial thrombosis; mild-to-severe thrombocytopenia; positive antiplatelet factor 4 (PF4)-polyanion antibodies or anti-PF4–heparin antibodies detected by ELISA; occurring 5–30 days after ChAdOx1 nCoV-19 (AstraZeneca) or Ad26. COV2.S (Johnson & Johnson/Janssen) vaccination and elevated D-dimer. From a pathophysiological point of view, VITT is an autoimmune disease characterized by the development of antibodies that directly activate platelets, causing thrombosis in the arterial or venous systems of the body. At the same time, the components of the vaccine serve as an antigen for the formation of autoantibodies, which enhance the production of platelet factor PF4, which contributes to the formation of blood clots. It has established that intravenous use of immunoglobulin at a dose of 1 g/kg of the patient's body weight per day, in addition to neutralizing antibodies, makes it possible to suppress VITT-mediated platelet activation. Fondaparinux, direct oral anticoagulants (DOACs), danaparoid or argatroban are the main anticoagulant drugs effective in the treatment of thrombotic conditions in VITT

COVID-19-вакциноиндуцированная иммунная тромботическая тромбоцитопения

The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) stimulated the development of highly effective vaccines that were produced with unprecedented speed with the use of new technologies. All the newly developed vaccines are highly effective with minimal adverse effects. Clinical introduction of the AstraZeneca Covid-19 vaccine has raised public alarm regarding the rare, but serious thrombotic events, known as vaccine-induced immune thrombotic thrombocytopenia (VITT). VITT is characterized clinical and laboratory syndromes like: venous (acute cerebral sinus venous thrombosis and abdominal vein thrombosis) or arterial thrombosis; mild-to-severe thrombocytopenia; positive antiplatelet factor 4 (PF4)-polyanion antibodies or anti-PF4–heparin antibodies detected by ELISA; occurring 5–30 days after ChAdOx1 nCoV-19 (AstraZeneca) or Ad26. COV2.S (Johnson & Johnson/Janssen) vaccination and elevated D-dimer. From a pathophysiological point of view, VITT is an autoimmune disease characterized by the development of antibodies that directly activate platelets, causing thrombosis in the arterial or venous systems of the body. At the same time, the components of the vaccine serve as an antigen for the formation of autoantibodies, which enhance the production of platelet factor PF4, which contributes to the formation of blood clots. It has established that intravenous use of immunoglobulin at a dose of 1 g/kg of the patient’s body weight per day, in addition to neutralizing antibodies, makes it possible to suppress VITT-mediated platelet activation. Fondaparinux, direct oral anticoagulants (DOACs), danaparoid or argatroban are the main anticoagulant drugs effective in the treatment of thrombotic conditions in VITT.Пандемия коронавирусной болезни COVID-19, сопровождающейся развитием острого тяжелого респираторного синдрома, потребовала разработки высокоэффективных вакцин, которые были созданы с беспрецедентной скоростью с использованием разнообразных технологий. Все разработанные вакцины обладают высокой эффективностью и минимальными побочными эффектами. Однако внедрение в клиническую практику вакцины AstraZeneca вызвало обеспокоенность общественности в связи с развитием редкого, но очень серьезного нежелательного осложнения — вакциноиндуцированной иммунной тромботической тромбоцитопении (ВИТТ). ВИТТ характеризуется развитием следующих клинико-лабораторных синдромов: венозных (чаще необычной локализации, например, в церебральных синусах и абдоминальных венах) или артериальных тромбозов; тромбоцитопении легкой или тяжелой степени с числом тромбоцитов < 150 × 10⁹/L; обнаружением антител к тромбоцитарному фактору 4 (PF4) путем иммуноферментного анализа; развитием симптомов заболевания в течение 5–30 дней (или 5–42 дней при изолированном ТГВ или ТЭЛА) после вакцинации против COVID-19 с помощью ChAdOx1 nCoV-19 (AstraZeneca) или Ad26.COV2.S (Johnson & Johnson/Janssen); увеличением уровня Д-димера (>4000 ФЭЕД). С патофизиологической позиции ВИТТ — аутоиммунное заболевание, характеризующееся образованием антител, которые непосредственно активируют тромбоциты, вызывая тромбозы в артериальной или венозной системах организма. При этом в качестве антигена для образования аутоантител служат компоненты вакцины, которые усиливают выработку тромбоцитарного фактора PF4, способствующего формированию тромбов. Установлено, что внутривенное применение иммуноглобулина в дозе 1 г/кг массы тела пациента в день, помимо нейтрализации антител, позволяет подавлять ВИТТ-опосредованную активацию тромбоцитов. Фондапаринукс, прямые пероральные антикоагулянты (ПОАК), данапароид или аргатробан являются основными антикоагулянтными препаратами, эффективными в лечении тромботических состояний при ВИТТ

Оценка риска и профилактика венозных тромбозов среди госпитализированных пациентов: результаты регионального мультицентрового исследования

Introduction. Venous thromboembolism (VTE) is a major public health issue that is frequently underestimated. The primary objective of this multicenter study was to identify patients at risk for VTE, and to define the rate of patients receiving appropriate prophylaxis in the regions of Kazakhstan.Materials and methods. Standardized case report forms were filled by trained medical doctors on one predefined day in selected hospitals. Data were analyzed by independent biostatistician. Risk of VTE was categorized according to Caprini score which was recommended by 2004 American College of Chest Physicians (ACCP) guidelines.Results. 432 patients from 4 regions of Kazakhstan; 169 (39.10%) medical patients and 263 (60.9%) surgical patients were eligible for the study. Patients were at low (10%), moderate (19.2%), high (33.6%) and very high risk (37.3%) for VTE. The main risk factors (RF) of VTE among hospitalized patients were heart failure (HF), obesity, prolonged bed rest, and the presence of acute non-infective inflammation. From total number of hospitalized patients with RF with indications to VTE prophylaxis, 58.1% of patients received pharmacological prophylaxis and only 24.6% of them received VTE prophylaxis according ACCP. On the other hand, 23.5% patients with the risk of VTE but who were not eligible for it received pharmacological prophylaxis.Conclusion. These results indicate the existence of inconsistency between eligibility for VTE prophylaxis on one hand and its application in practice (p < 0.001). Risk factors for VTE and eligibility for VTE prophylaxis are common, but VTE prophylaxis and guidelines application are low.Введение. Венозная тромбоэмболия – недооцененная проблема современной медицины, которая проявляется двумя клиническими формами в виде тромбоза глубоких вен и тромбоэмболии легочных артерий. Основной целью данного многоцентрового перекрестного исследования явилась идентификация пациентов с риском ВТЭ и определение доли пациентов, получающих надлежащую профилактику согласно рекомендациям Американской коллегии грудных специалистов.Материалы и методы. Специально обученные специалисты заполняли стандартную индивидуальную регистрационную карту в течение одного определенного дня в выбранных больницах. Уровень риска ВТЭ оценивали согласно рекомендациям ACCP-2004 по шкале Caprini для выбора соответствующей профилактики.Результаты. В исследование включено 432 пациента из 4 регионов Казахстана, из которых 169 (39,1%) – пациенты терапевтического профиля и 263 (60,9%) – хирургического профиля. Результаты исследования свидетельствуют о высокой встречаемости (90%) факторов риска ВТЭ среди госпитализированных пациентов независимо от профиля патологии с долей пациентов низкого (10%), умеренного (19,2%), высокого (33,6%) и очень высокого риска (19,2%) ВТЭ. Основными ФР развития ВТЭ были хроническая сердечная недостаточность, ожирение, длительное пребывание пациентов на постельном режиме и наличие острого неинфекционного воспаления. Из общего количества госпитализированных пациентов с ФР, кому была показана профилактика, 58,1% пациентов получали фармакологическую профилактику. Из этого количества 24,6% пациентов получили профилактику ВТЭ согласно рекомендациям АССР в правильной дозировке и длительности. В группе пациентов с рисками тромбозов, но с противопоказанием к проведению профилактики в 23,5% случаях была проведена профилактика.Выводы. Результаты исследования указывают на наличие несогласованности между существующими рекомендациями по профилактике ВТЭ и результатами реальной клинической практики, т. е. отсутствие профилактики у пациентов высокого риска и проведение профилактики в группах пациентов, кому профилактика не требовалась (р < 0,001)

A rare case of deep vein and right atrial thrombosis in a patient with chronic heart failure and pulmonary embolism

Deep vein thrombosis (DVT) is frequently observed in patients with chronic heart failure (CHF), increasing the risk of pulmonary embolism (PE). Clinical evaluation of CHF patients with suspected acute PE is challenging since these diseases share several symptoms and signs such as dyspnea. Thus, it is intuitive that correct and fast diagnosis of PE in these patients might be able to significantly change their clinical outcome. In the present report, we describe a rare case of a patient with CHF and PE due to a huge thrombosis of deep veins and of right atrium in whom echo evaluation permitted the correct diagnosis and therapy. [1,2]. This variability might be due to the different sensitivity of diagnostic criteria in reports: those hospitals, in which the screening for DVT is more accurate, are likely to find more cases of DVT and pulmonary embolism (PE) [3]. Myocardial infarction and heart failure increase the risk of PE. Conversely, patients with DVT have an increased risk of developing myocardial infarction and stroke [4]. Thus, a correct and fast diagnosis of PE in these patients plays a pivotal role to change their clinical outcome. In the present report, we describe the case of a patient with CHF complicated by PE due to a huge venous thrombosis that extended from pheripheral vein till the right atrium, where echocardiographic evaluation showed a rare image of thrombus floating in the cavity of cardiac chamber

Uric acid plasma levels are associated with C-reactive protein concentrations and the extent of coronary artery lesions in patients with acute coronary syndromes

Many studies have pointed out that inflammation plays a pivotal role in pathophysiology of acute coronary syndromes (ACS) because several inflammatory molecules impair the endothelial functions in the coronary circulation and promote atherothrombotic events. Recently, many clinical/experimental evidences indicate that elevated plasma levels of uric acid (UA) might be considered a risk factor for developing ACS. It has been reported that elevated UA doses impair physiologic functions of endothelial cells, shifting them toward a pro atherothrombotic phenotype. In the present manuscript, we investigated the relationship between UA plasma levels, inflammatory burden, and extension of coronary atherosclerotic disease in patients with ACS. Patients with a clinical presentation of ACS (ST-elevated and non-ST-elevated myocardial infarction) admitted to the Vanvitelli Catheterization Laboratory at Monaldi Hospital in 2019, before the COVID-19 pandemia, were retrospectively analyzed. Biochemical profile, type of ACS presentation, as well as extension of coronary atherosclerosis were assessed. A total of 132 ACS patients were included in the analysis, and grouped into 3 tertiles according to the UA values (UA 6.15 mg/dl). Patients with UA plasma levels ≥ 6.15 mg/dL showed higher levels of C-reactive protein (mean of 5.1 mg/dL) as compared to patients with lower UA plasma levels. Moreover, the former group of patients showed higher levels of cardiac troponin and CPK, and presented more often with multivessel disease and complex coronary stenosis (type C of Ellis classification). Even though monocentric and with limited sample size, the present study shows that plasma levels of UA and hs-CRP are elevated in ACS patients and are associated with a more severe coronary disease, suggesting a potential role of UA in the pathophysiology of acute coronary events

Effects of colchicine on tissue factor in oxLDL-activated T-lymphocytes

Several studies have shown that T-cells might be involved in pathophysiology of acute coronary syndromes (ACS). Tissue factor (TF) plays a key role in ACS. Many evidences have indicated that some statins reduce TF expression in several cell types. However, literature about rosuvastatin and TF and about statins effects on T-cells is still scanty. Colchicine is an anti-inflammatory drug recently proven to have beneficial effects in ACS via unknown mechanisms. This study investigates the effects of colchicine and rosuvastatin on TF expression in oxLDL-activated T-cells. T-cells, isolated from buffy coats of healthy volunteers, were stimulated with oxLDL (50 \ub5g/dL). T-cells were pre-incubated with colchicine (10 \ub5M) or rosuvastatin (5 \ub5M) for 1 h and then stimulated with oxLDL (50 \u3bcg/mL). TF gene (RT-PCR), protein (western blot), surface expression (FACS) and procoagulant activity (FXa generation assay) were measured. NF-\u3baB/I\u3baB axis was examined by western blot analysis and translocation assay. Colchicine and rosuvastatin significantly reduced TF gene, and protein expression and procoagulant activity in oxLDL stimulated T-cells. This effect was associated with a significant reduction in TF surface expression as well as its procoagulant activity. These phenomena appear modulated by drug effects on the transcription factor NF-kB. Rosuvastatin and colchicine prevent TF expression in oxLDL-stimulated T-cells by modulating the NF-\u3baB/I\u3baB axis. Thus, we speculate that this might be another mechanism by which these drugs exert benefic cardiovascular effects

2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS

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2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European respiratory society (ERS)

Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in proposing the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate

2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS)

none107siNon presentemixedValgimigli, Marco*; Bueno, Héctor; Byrne, Robert A.; Collet, Jean-Philippe; Costa, Francesco; Jeppsson, Anders; Kastrati, Adnan; Kolh, Philippe; Mauri, Laura; Montalescot, Gilles; Neumann, Franz-Josef; Petricevic, Mate; Roffi, Marco; Steg, Philippe Gabriel; Zamorano, Jose Luis; Levine, Glenn N.; Badimon, Lina; Vranckx, Pascal; Agewall, Stefan; Andreotti, Felicita; Antman, Elliott; Barbato, Emanuele; Bassand, Jean-Pierre; Bugiardini, Raffaele; Cikirikcioglu, Mustafa; Cuisset, Thomas; De Bonis, Michele; Delgado, Victora; Fitzsimons, Donna; Galiè, Nazzareno; Gilard, Martine; Hamm, Christian W.; Ibanez, Borja; James, Stefan; Knuuti, Juhani; Landmesser, Ulf; Leclercq, Christophe; Lettino, Maddalena; Lip, Gregory; Piepoli, Massimo Francesco; Pierard, Luc; Schwerzmann, Markus; Sechtem, Udo; Simpson, Iain A.; Uva, Miguel Sousa; Stabile, Eugenio; Storey, Robert F.; Tendera, Michal; Van De Werf, Frans; Verheugt, Freek; Aboyans, Victor; Windecker, Stephan; Coca, Antonio; Coman, Ioan Mircea; Dean, Veronica; Delgado, Victoria; Gaemperli, Oliver; Hindricks, Gerhard; Iung, Bernard; Jüni, Peter; Katus, Hugo A.; Lancellotti, Patrizio; McDonagh, Theresa; Ponikowski, Piotr; Richter, DImitrios J.; Shlyakhto, Evgeny; Roithinger, Franz Xaver; Aliyev, Farid; Stelmashok, Valeriy; Desmet, Walter; Postadzhiyan, Arman; Georghiou, Georgios P.; Motovska, Zuzana; Grove, Erik Lerkevang; Marandi, Toomas; Kiviniemi, Tuomas; Kedev, Sasko; Massberg, Steffen; Alexopoulos, DImitrios; Kiss, Robert Gabor; Gudmundsdottir, Ingibjorg Jona; McFadden, Eugène P.; Lev, Eli; De Luca, Leonardo; Sugraliyev, Akhmetzhan; Haliti, Edmond; Mirrakhimov, Erkin; Latkovskis, Gustavs; Petrauskiene, Birute; Huijnen, Steve; Magri, Caroline Jane; Cherradi, Rhizlan; Ten Berg, Jurrien M.; Eritsland, Jan; Budaj, Andrzej; Aguiar, Carlos Tavares; Duplyakov, Dmitry; Zavatta, Marco; Antonijevic, Nebojsa M.; Fras, Zlatko; Montoliu, Antonio Tello; Varenhorst, Christoph; Tsakiris, DImitri; Addad, Faouzi; Aydogdu, Sinan; Parkhomenko, Alexander; Kinnaird, TimValgimigli, Marco*; Bueno, Héctor; Byrne, Robert A.; Collet, Jean-Philippe; Costa, Francesco; Jeppsson, Anders; Kastrati, Adnan; Kolh, Philippe; Mauri, Laura; Montalescot, Gilles; Neumann, Franz-Josef; Petricevic, Mate; Roffi, Marco; Steg, Philippe Gabriel; Zamorano, Jose Luis; Levine, Glenn N.; Badimon, Lina; Vranckx, Pascal; Agewall, Stefan; Andreotti, Felicita; Antman, Elliott; Barbato, Emanuele; Bassand, Jean-Pierre; Bugiardini, Raffaele; Cikirikcioglu, Mustafa; Cuisset, Thomas; De Bonis, Michele; Delgado, Victora; Fitzsimons, Donna; Galiè, Nazzareno; Gilard, Martine; Hamm, Christian W.; Ibanez, Borja; James, Stefan; Knuuti, Juhani; Landmesser, Ulf; Leclercq, Christophe; Lettino, Maddalena; Lip, Gregory; Piepoli, Massimo Francesco; Pierard, Luc; Schwerzmann, Markus; Sechtem, Udo; Simpson, Iain A.; Uva, Miguel Sousa; Stabile, Eugenio; Storey, Robert F.; Tendera, Michal; Van De Werf, Frans; Verheugt, Freek; Aboyans, Victor; Windecker, Stephan; Coca, Antonio; Coman, Ioan Mircea; Dean, Veronica; Delgado, Victoria; Gaemperli, Oliver; Hindricks, Gerhard; Iung, Bernard; Jüni, Peter; Katus, Hugo A.; Lancellotti, Patrizio; McDonagh, Theresa; Ponikowski, Piotr; Richter, DImitrios J.; Shlyakhto, Evgeny; Roithinger, Franz Xaver; Aliyev, Farid; Stelmashok, Valeriy; Desmet, Walter; Postadzhiyan, Arman; Georghiou, Georgios P.; Motovska, Zuzana; Grove, Erik Lerkevang; Marandi, Toomas; Kiviniemi, Tuomas; Kedev, Sasko; Massberg, Steffen; Alexopoulos, DImitrios; Kiss, Robert Gabor; Gudmundsdottir, Ingibjorg Jona; McFadden, Eugène P.; Lev, Eli; De Luca, Leonardo; Sugraliyev, Akhmetzhan; Haliti, Edmond; Mirrakhimov, Erkin; Latkovskis, Gustavs; Petrauskiene, Birute; Huijnen, Steve; Magri, Caroline Jane; Cherradi, Rhizlan; Ten Berg, Jurrien M.; Eritsland, Jan; Budaj, Andrzej; Aguiar, Carlos Tavares; Duplyakov, Dmitry; Zavatta, Marco; Antonijevic, Nebojsa M.; Fras, Zlatko; Montoliu, Antonio Tello; Varenhorst, Christoph; Tsakiris, DImitri; Addad, Faouzi; Aydogdu, Sinan; Parkhomenko, Alexander; Kinnaird, Ti

2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European respiratory society (ERS) : The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC)

Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in proposing the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate