Цель. Клиническая характеристика диссеминированного внутрисосудистого свертывания крови (ДВС) при инфекции COVID-19 и оценка эффективности комплексной терапии этого синдрома на этапах профилактики и лечения различных осложнений. Материалы и методы. Изучение публикаций проводили через поисковые системы в Интернете по ключевым словам. Для диагностики инфекции использовалась программа COVID-19 на платформе MeDiCase, находящаяся в открытом доступе в сети Интернет на сайте по ссылке www.medicase.pro, которая с чувствительностью 89,47% позволяет предположить диагноз. Под наблюдением состояли
85 больных с острым COVID-19 с легким и среднетяжелым течением болезни в возрасте от 11 до 81 года. Наличие возбудителя подтверждено иммунологически у 12% больных, в остальных случаях диагноз основывался на результатах автоматизированного опроса в системе MeDiCase. Всем больным согласно рекомендациям МГНОТ назначался один из оральных прямых антикоагулянтов – Эликвис в дозе 5 мг 2 раза в сутки, Ксарелто в дозе 10 мг 2 раза в сутки или Прадакса в дозе 110 мг 2 раза в сутки на срок не менее 2 нед. Все остальные препараты с противовирусным, иммуномодулирующим действием, антибиотики отменялись. Результаты. Наличие ДВС-синдрома обосновывается морфологической картиной изменений в органах и тканях, клиническими (гематомно-петехиальный тип кровоточивости в сочетании с тромбоэмболическим синдромом и наличием тромбоваскулита) и лабораторными изменениями: повышение уровня растворимых комплексов фибрин-мономеров, Д-димера, гиперфибриногенемией, реже – тромбоцитопенией, нарушением фибринолитической активности. Редко встречаются феномен потребления факторов свертывания и профузные кровотечения. В лечении ДВС-синдрома используются прямые антикоагулянты, трансфузии свежезамороженной плазмы и плазмаферез. В работе приведены собственные позитивные результаты раннего назначения на амбулаторном этапе прямых оральных антикоагулянтов в профилактических дозах (ни одного случая прогрессирования заболевания), отдельные случаи использования свежезамороженной плазмы и плазмафереза. Заключение. ДВС-синдром с развитием тромбоваскулита является важнейшим патогенетическим механизмом развития микротромботических и геморрагических нарушений в органах при инфекции COVID-19, приводящих к нарушению функций легких, головного мозга и других нервных тканей, почек, тромбоэмболическим осложнениям и др. Многие симптомы болезни могут быть связаны с нарушением нервной регуляции функций органов и систем. Профилактика тромбоваскулита эффективна уже на стадии первой манифестации болезни с амбулаторным применением прямых антикоагулянтов (оральных, низкомолекулярных гепаринов).
В случае более тяжелых проявлений (осложнений) болезни эффективно дополнительное применение свежезамороженной плазмы и плазмафереза.
Aim. Clinical characteristics of disseminated intravascular coagulation (DIC) in COVID-19 infection and assessment of the effectiveness of complex therapy for this syndrome at the stages of prevention and treatment of various complications. Materials and methods. The study of publications was carried out through search engines on the Internet using keywords. To diagnose the infection, the COVID-19 program was used on the MeDiCase platform, which is publicly available on www.medicase.pro, which suggests a diagnosis with a sensitivity of 89.47%. The study included 85 patients with acute COVID-19 with mild to moderate disease, aged 11 to 81 years. The presence of the pathogen was confirmed immunologically in 12% of patients; in other cases, the diagnosis was based on the results of an automated survey in the MeDiCase system. All patients, according to the MGNOT recommendations, were prescribed one of the oral direct anticoagulants - Eliquis at a dose of 5 mg 2 times a day, Ksarelto at a dose of 10 mg 2 times a day or Pradax at a dose of 110 mg 2 times a day for at least 2 weeks. All other drugs with antiviral, immunomodulatory effects, antibiotics were canceled. Results. The presence of DIC is substantiated by the morphological picture of changes in organs and tissues, clinical (hematoma-petechial type of bleeding in combination with thromboembolic syndrome and the presence of thrombovasculitis) and laboratory changes: an increase in the level of soluble fibrin-monomer complexes, D-dimer, hyperfibrinogenaemia, less often - thrombocytopenia, violation of fibrinolytic activity. The phenomenon of consumption of clotting factors and profuse bleeding are rare. Direct anticoagulants, fresh frozen plasma transfusions and plasmapheresis are used in the treatment of disseminated intravascular coagulation. The paper presents its own positive results of early prescription at the outpatient stage of direct oral anticoagulants in prophylactic doses (no case of disease progression), individual cases of the use of fresh frozen plasma and plasapheresis. Conclusion. DIC syndrome with the development of thrombovasculitis is the most important pathogenetic mechanism for the development of microthrombotic and hemorrhagic disorders in organs during infection with COVID-19, leading to dysfunction of the lungs, brain and other nerve tissues, kidneys, thromboembolic complications, etc. Many symptoms of the disease may be associated with a violation of the nervous regulation of the functions of organs and systems. Prevention of thrombovasculitis is effective already at the stage of the first manifestation of the disease with the outpatient use of direct anticoagulants (oral, low molecular weight heparins). In case of more severe manifestations (complications) of the disease, additional use of freshly frozen plasma and plasmapheresis is effective.
1. Воробьев П.А., Воробьев А.П., Краснова Л.С. Результаты апробации автоматизированного опросника для выявления респираторных инфекций, включая COVID-19. Клин. геронтология. 2020;9-10:27 [Vorobyev PA, Vorobiev AP, Krasnova LS. Results of testing an automated questionnaire for respiratory infections, including COVID-19. Clinical Gerontology. 2020;9-10:27 (In Russ.)]. https://kg.newdiamed.ru/issue/id117237
2. Рекомендации МГНОТ по диагностике и интенсивной терапии синдрома диссеминированного внутрисосудистого свертывания крови при вирусном поражении легких. Под ред. проф. Воробье-
ва П.А. и проф. Елыкомова В.А. Проблемы стандартизации в здравоохранении. 2020;5-6 [MGNOT recommendations for the diagnosis and intensive care of disseminated intravascular coagulation syndrome in viral lung disease. Ed. by prof. Vorobyov PA and prof. Elykomov VA. Problems of standardization in healthcare. 2020;5-6 (In Russ.)]. doi: 10.26347/1607-2502202005-06099-111
3. Заратьянц О.В., Самсонова М.В., Михалева Л.М. и др. Патологическая анатомия COVID-19. Атлас. Под общ. ред. О.В. Заратьянца. М.: ДЗМ, 2020 [Zaratiyants OV, Samsonova MV, Mikhaleva LM, et al. Pathological anatomy of COVID-19. Medical atlas. Ed. by Zaratiyants OV. Moscow: Moscow Department of Healthcare, 2020 (In Russ.)]. https://mosgorzdrav.ru/uploads/imperavi/ru-RU/patanatomiya_COVID-19_fullv2_compressed.pdf.
4. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Ingl J Med. 2020;383(2):120-8. doi: 10.1056/NEJMoa2015432
5. Doevelaar AAN, Bachmann M, Hoelzer B, et al. COVID-19 is associated with relative ADAMTS13 deficiency and VWF multimer formation resembling TTP. medRxiv. 2020. doi: 10.1101/2020.08.23.20177824
6. Antithrombotic Therapy in Patients with COVID-19. U.S. Department of Health & Human Services, National Institutes of Health. https://www.nih.gov/coronavirus.
7. Воробьев П.А., Воробьев А.П., Краснова Л.С. Поражение центральной нервной системы при инфекции, вызванной вирусом COVID-19. Клин. геронтология. 2020;9-10:26-7 [Vorobyov PA, Vorobiev AP, Krasnova LS. Damage to the central nervous system in infection caused by the COVID-19 virus. Clinical Gerontology. 2020;9-10:26-7 (In Russ.)]. https://kg.newdiamed.ru/issue/id117237
8. Politi LS, Salsano E, Grimaldi M. Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia. JAMA Neurol. 2020;77(8):1028-9. doi: 10.1001/jamaneurol.2020.2125
9. Lu Y, Li X, Geng D, et al. Cerebral Micro-Structural Changes in COVID-19 Patients An MRI-based 3-month Follow-up Study. EClinicalMedicine. 2020;25:100484. doi: 10.1016/j.eclinm.2020.100484
10. Bowles L, Platton S, Yartey N, et al. Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19. N Engl J Med. 2020;383(3):288-90. doi: 10.1056/NEJMc2013656
11. Pinto AA, Carroll LS, Nar V, et al. CNS inflammatory vasculopathy with antimyelin oligodendrocyte glycoprotein antibodies in COVID-19. Neurol Neuroimmunol Neuroinflamm. 2020;7(5). doi: 10.1212/NXI.0000000000000813
12. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta. 2020;506:145-8. doi: 10.1016/j.cca.2020.03.022
13. Zuo Y, Warnock M, Harbaugh A, et al. Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients. medRxiv. 2020. doi: 10.1101/2020.08.29.20184358
14. Moore HB, Barrett CD, Moore EE, et al. Is there a role for tissue plasminogen activator as a novel treatment for refractory COVID-19 associated acute respiratory distress syndrome? Trauma Acute Care Surg. 2020;88(6):713-4. doi: 10.1097/TA.0000000000002694
15. Yu B, Li X, Chen J, et al. Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis.
J Thromb Thrombolysis. 2020;50:548-57. doi: 10.1007/s11239-020-02171-y
16. Временные методические рекомендации – профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19). Минздрав России. Версия VI. 28.04.2020 [Temporary guidelines – prevention, diagnosis and treatment of new coronavirus infection (COVID-19). Ministry of Health of Russia. Version VI. 28.04.2020 (In Russ.)]. https://static-1.rosminzdrav.ru/system/attachments/attaches/000/050/116/original/28042020_МR_COVID-1....
17. Delirium, rare brain inflammation and stroke linked to COVID-19. University College London. https://www.ucl.ac.uk/news/2020/jul/delirium-rare-brain-inflammation-and-stroke-linked-covid-19.
18. Paranjpe I, Fuster V, Lala A, et al. Association of Treatment Dose Anticoagulation With In-Hospital Survival Among Hospitalized Patients With COVID-19. J Am Coll Cardiol. 2020;76(1):122-4. doi: 10.1016/j.jacc.2020.05.001
19. Nadkarni GN, Lala A, Bagiella E, et al. Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19. J Am Coll Cardiol. 2020;76(16):1815-26. doi: 10.1016/j.jacc.2020.08.041
20. EVMS critical care covid-19 management protocol Developed and updated by P. Marik, MD Chief of Pulmonary and Critical Care Medicine Eastern Virginia Medical School. Norfolk, VA, 2020.
21. Самойлов А.С., Удалов Ю.Д., Кругляков Н.М. и др. Опыт успешного применения новой методики лечения тяжелой формы COVID-19. Клин. практика. 2020;11(2):93-100 [Samoylov AS, Udalov YD, Kruglyakov NM, et al. A clinical case of successful application of a new treatment method for severe COVID-19. Journal of Clinical Practice. 2020;11(2):93-100 (In Russ.)]. doi: 10.17816/clinpract34529
22. Chang JC. Acute Respiratory Distress Syndrome as an Organ Phenotype of Vascular Microthrombotic Disease: Based on Hemostatic Theory and Endothelial Molecular Pathogenesis. Clin Appl Thromb Hemost. 2019;25:1076029619887437. doi: 10.1177/1076029619887437
23. Adeli SH, Asghari A, Tabarraii R, et al. Therapeutic plasma exchange as a rescue therapy in patients with coronavirus disease 2019: a case series. Pol Arch Intern Med. 2020;130:455-8. doi: 10.20452/pamw.15340
24. Fernandez J, Gratacos-Ginès J, Olivas P, et al. Plasma Exchange: An Effective Rescue Therapy in Critically Ill Patients With Coronavirus Disease 2019 Infection. Crit Care Med. 2020. doi: 10.1097/CCM.0000000000004613
________________________________________________
1. Vorobyev PA, Vorobiev AP, Krasnova LS. Results of testing an automated questionnaire for respiratory infections, including COVID-19. Clinical Gerontology. 2020;9-10:27 (In Russ.) https://kg.newdiamed.ru/issue/id117237
2. MGNOT recommendations for the diagnosis and intensive care of disseminated intravascular coagulation syndrome in viral lung disease. Ed. by prof. Vorobyov PA and prof. Elykomov VA. Problems of standardization in healthcare. 2020;5-6 (In Russ.) doi: 10.26347/1607-2502202005-06099-111
3. Zaratiyants OV, Samsonova MV, Mikhaleva LM, et al. Pathological anatomy of COVID-19. Medical atlas. Ed. by Zaratiyants OV. Moscow: Moscow Department of Healthcare, 2020 (In Russ.) https://mosgorzdrav.ru/uploads/imperavi/ru-RU/patanatomiya_COVID-19_fullv2_compressed.pdf.
4. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Ingl J Med. 2020;383(2):120-8. doi: 10.1056/NEJMoa2015432
5. Doevelaar AAN, Bachmann M, Hoelzer B, et al. COVID-19 is associated with relative ADAMTS13 deficiency and VWF multimer formation resembling TTP. medRxiv. 2020. doi: 10.1101/2020.08.23.20177824
6. Antithrombotic Therapy in Patients with COVID-19. U.S. Department of Health & Human Services, National Institutes of Health. https://www.nih.gov/coronavirus.
7. Vorobyov PA, Vorobiev AP, Krasnova LS. Damage to the central nervous system in infection caused by the COVID-19 virus. Clinical Gerontology. 2020;9-10:26-7 (In Russ.) https://kg.newdiamed.ru/issue/id117237
8. Politi LS, Salsano E, Grimaldi M. Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia. JAMA Neurol. 2020;77(8):1028-9. doi: 10.1001/jamaneurol.2020.2125
9. Lu Y, Li X, Geng D, et al. Cerebral Micro-Structural Changes in COVID-19 Patients An MRI-based 3-month Follow-up Study. EClinicalMedicine. 2020;25:100484. doi: 10.1016/j.eclinm.2020.100484
10. Bowles L, Platton S, Yartey N, et al. Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19. N Engl J Med. 2020;383(3):288-90. doi: 10.1056/NEJMc2013656
11. Pinto AA, Carroll LS, Nar V, et al. CNS inflammatory vasculopathy with antimyelin oligodendrocyte glycoprotein antibodies in COVID-19. Neurol Neuroimmunol Neuroinflamm. 2020;7(5). doi: 10.1212/NXI.0000000000000813
12. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta. 2020;506:145-8. doi: 10.1016/j.cca.2020.03.022
13. Zuo Y, Warnock M, Harbaugh A, et al. Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients. medRxiv. 2020. doi: 10.1101/2020.08.29.20184358
14. Moore HB, Barrett CD, Moore EE, et al. Is there a role for tissue plasminogen activator as a novel treatment for refractory COVID-19 associated acute respiratory distress syndrome? Trauma Acute Care Surg. 2020;88(6):713-4. doi: 10.1097/TA.0000000000002694
15. Yu B, Li X, Chen J, et al. Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis.
J Thromb Thrombolysis. 2020;50:548-57. doi: 10.1007/s11239-020-02171-y
16. Temporary guidelines – prevention, diagnosis and treatment of new coronavirus infection (COVID-19). Ministry of Health of Russia. Version VI. 28.04.2020 (In Russ.) https://static-1.rosminzdrav.ru/system/attachments/attaches/000/050/116/original/28042020_МR_COVID-1....
17. Delirium, rare brain inflammation and stroke linked to COVID-19. University College London. https://www.ucl.ac.uk/news/2020/jul/delirium-rare-brain-inflammation-and-stroke-linked-covid-19.
18. Paranjpe I, Fuster V, Lala A, et al. Association of Treatment Dose Anticoagulation With In-Hospital Survival Among Hospitalized Patients With COVID-19. J Am Coll Cardiol. 2020;76(1):122-4. doi: 10.1016/j.jacc.2020.05.001
19. Nadkarni GN, Lala A, Bagiella E, et al. Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19. J Am Coll Cardiol. 2020;76(16):1815-26. doi: 10.1016/j.jacc.2020.08.041
20. EVMS critical care covid-19 management protocol Developed and updated by P. Marik, MD Chief of Pulmonary and Critical Care Medicine Eastern Virginia Medical School. Norfolk, VA, 2020.
21. Samoylov AS, Udalov YD, Kruglyakov NM, et al. A clinical case of successful application of a new treatment method for severe COVID-19. Journal of Clinical Practice. 2020;11(2):93-100 (In Russ.) doi: 10.17816/clinpract34529
22. Chang JC. Acute Respiratory Distress Syndrome as an Organ Phenotype of Vascular Microthrombotic Disease: Based on Hemostatic Theory and Endothelial Molecular Pathogenesis. Clin Appl Thromb Hemost. 2019;25:1076029619887437. doi: 10.1177/1076029619887437
23. Adeli SH, Asghari A, Tabarraii R, et al. Therapeutic plasma exchange as a rescue therapy in patients with coronavirus disease 2019: a case series. Pol Arch Intern Med. 2020;130:455-8. doi: 10.20452/pamw.15340
24. Fernandez J, Gratacos-Ginès J, Olivas P, et al. Plasma Exchange: An Effective Rescue Therapy in Critically Ill Patients With Coronavirus Disease 2019 Infection. Crit Care Med. 2020. doi: 10.1097/CCM.0000000000004613
1 РОО «Московское городское научное общество терапевтов», Москва, Россия;
2 ФГБОУ ВО «Московский государственный университет пищевых производств», Москва, Россия;
3 Алтайский филиал ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России, Барнаул, Россия;
4 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
5 Научный центр реконструктивно-восстановительной хирургии Минздрава Кыргызской Республики, Бишкек, Кыргызстан;
6 Университет им. Эразма Роттердамского, Роттердам, Голландия
________________________________________________
P.A. Vorobyev1,2, A.P. Momot3, L.S. Krasnova4, A.P. Vorobiev1, A.K. Talipov5,6
1 Moscow City Scientific Society of Physicians, Moscow, Russia;
2 Moscow State University of Food Production, Moscow, Russia;
3 Altai branch of the National Medical Research Center of Hematology, Barnaul, Russia;
4 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
5 Scientific Center for Reconstructive Surgery, Bishkek, Kyrgyzstan;
6 Erasmus University Rotterdam, Rotterdam, Holland