akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2021.265akusherstvo-1138Research ArticleEDITORIALРЕДАКЦИОННАЯ СТАТЬЯCOVID-19 and thrombotic microangiopathyCOVID-19 и тромботическая микроангиопатияhttps://orcid.org/0000-0001-7441-2778СлуханчукЕ. В.SluhanchukE. V.

Слуханчук Екатерина Викторовна – к.м.н., доцент кафедры акушерства и гинекологии Клинического института детского здоровья имени Н.Ф. Филатова; врач акушер-гинеколог отделения абдоминальной хирургии и онкологии 2

119991, Москва, ул. Большая Пироговская, д. 2, стр. 4119991, Москва, Абрикосовский пер., д. 2

Ekaterina V. Slukhanchuk – MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health; Obstetrician-Gynecologist, Department of Abdominal Surgery and Oncology 2

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 1199912 Abrikosovskiy Lane, Moscow, 119991

beloborodova@rambler.ruhttps://orcid.org/0000-0001-8404-1042БицадзеВ. О.BitsadzeV. O.

Бицадзе Виктория Омаровна – д.м.н., профессор РАН, профессор кафедры акушерства и гинекологии Клинического института детского здоровья имени Н.Ф. Филатова. Scopus Author ID: 6506003478. Researcher ID: F-8409-2017

119991, Москва, ул. Большая Пироговская, д. 2, стр. 4

Victoria O. Bitsadze – MD, Dr Sci Med, Professor of RAS, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health. Scopus Author ID: 6506003478. Researcher ID: F-8409-2017

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991

https://orcid.org/0000-0002-0725-9686ХизроеваД. Х.KhizroevaJ. Kh.

Хизроева Джамиля Хизриевна – д.м.н., профессор кафедры акушерства и гинекологии Клинического института детского здоровья имени Н.Ф. Филатова. Scopus Author ID: 57194547147. Researcher ID: F-8384-2017

119991, Москва, ул. Большая Пироговская, д. 2, стр. 4

Jamilya Kh. Khizroeva – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health. Scopus Author ID: 57194547147. Researcher ID: F-8384-2017

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991

https://orcid.org/0000-0002-3628-0804ТретьяковаМ. В.TretyakovaM. V.

Третьякова Мария Владимировна – к.м.н., врач акушер-гинеколог, ассистент кафедры акушерства и гинекологии Клинического института детского здоровья имени Н.Ф. Филатова

119991, Москва, ул. Большая Пироговская, д. 2, стр. 4

Maria V. Tretyakova – MD, PhD, Obstetrician-Gynecologist, Assistant, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991

https://orcid.org/0000-0002-9783-1796ШкодаА. С.ShkodaA. S.

Шкода Андрей Сергеевич – д.м.н., профессор, главный врач

123423, Москва, ул. Саляма Адиля, д. 2/44

Andrey S. Shkoda – MD, Dr Sci Med, Professor, Chief Physician

2/44 Salyama Adilya Str., Moscow, 123423

https://orcid.org/0000-0001-7758-4006АртюковО. П.ArtyukovO. P.

Артюков Олег Петрович – к.м.н., доцент кафедры нервных болезней и нейрохирургии

117198, Москва, ул. Миклухо-Маклая, д. 6

Oleg P. Artyukov – MD, PhD, Associate Professor, Department of Nervous Diseases and Neurosurgery

6 Miklukho-Maklaya Str., Moscow, 117198

https://orcid.org/0000-0001-5888-0774ЦибизоваВ. И.TsibizovaV. I.

Цибизова Валентина Ивановна – к.м.н., акушер-гинеколог НИЛ оперативной гинекологии Института перинатологии и педиатрии; врач отделения функциональной и ультразвуковой диагностики

197341, Санкт-Петербург, ул. Аккуратова, д. 2

Valentina I. Tsibizova – MD, PhD, Obstetrician-Gynecologist, Research Laboratory of Operative Gynecology, Institute of Perinatology and Pediatrics; Physician, Department of Functional and Ultrasound Diagnostics

2 Akkuratova Str., Saint Petersburg, 197341

МищенкоА. Л.MishchenkoA. L.

Мищенко Александр Леонидович – д.м.н., профессор кафедры акушерства и гинекологии Клинического института детского здоровья имени Н.Ф. Филатова

119991, Москва, ул. Большая Пироговская, д. 2, стр. 4

Alexander L. Mishchenko – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991

https://orcid.org/0000-0002-7756-8935ГригорьеваК. Н.GrigorievaK. N.

Григорьева Кристина Николаевна – ординатор кафедры акушерства и гинекологии Клинического института детского здоровья имени Н.Ф. Филатова

119991, Москва, ул. Большая Пироговская, д. 2, стр. 4

Kristina N. Grigoreva – MD, Medical Resident, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991

https://orcid.org/0000-0002-9899-9910ГриЖ.-К.GrisJ.-С.

Гри Жан-Кристоф – д.м.н., профессор кафедры акушерства и гинекологии Клинического института детского здоровья имени Н.Ф. Филатова; профессор гематологии, университет Монпелье. Scopus Author ID: 7005114260. Researcher ID: AAA2923-2019

119991, Москва, ул. Большая Пироговская, д. 2, стр. 4Франция, 34090, Монпелье, ул. Огюста Бруссоне, д. 163

Jean-Christophe Gris – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health; Professor of Haematology, Head of the Laboratory of Haematology, Faculty of Biological and Pharmaceutical Sciences. Scopus Author ID: 7005114260. Researcher ID: AAA-2923-2019

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991163 Rue Auguste Broussonnet, Montpellier, 34090, France

https://orcid.org/0000-0002-9576-1368ЭлаламиИ.ElalamyE.

Элалами Исмаил – д.м.н., профессор кафедры акушерства и гинекологии Клинического института детского здоровья имени Н.Ф. Филатова; профессор; директор гематологии Центра Тромбозов. Scopus Author ID: 7003652413. Researcher ID: AAC-9695-2019

119991, Москва, ул. Большая Пироговская, д. 2, стр. 4Франция, 75006, Париж, Улица медицинского факультета, д. 12Франция, 75020, Париж, Китайская улица, д. 4

Ismail Elalamy – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health; Professor; Director of Hematology, Department of Thrombosis Center. Scopus Author ID: 7003652413. Researcher ID: AAC-9695-2019

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 11999112 Rue de l’École de Médecine, 75006, Paris, France4 Rue de la Chine, 75020, Paris, France

https://orcid.org/0000-0001-7415-4633МакацарияА. Д.MakatsariyaA. D.

Макацария Александр Давидович – д.м.н., профессор, академик РАН, зав. кафедрой акушерства и гинекологии Клинического института детского здоровья имени Н.Ф. Филатова. Scopus Author ID: 57222220144. Researcher ID: M-5660-2016

119991, Москва, ул. Большая Пироговская, д. 2, стр. 4

Alexander D. Makatsariya – MD, Dr Sci Med, Academician of RAS, Professor, Head of the Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health. Scopus Author ID: 57222220144. Researcher ID: M-5660-2016

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991

ФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет); ФГБНУ «Российский научный центр хирургии имени академика Б.В. Петровского»РоссияSechenov University; Petrovsky National Research Centre of SurgeryRussian FederationФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияSechenov UniversityRussian FederationГБУЗ «Городская клиническая больница № 67 имени Л.А. Ворохобова Департамента здравоохранения города Москвы»РоссияVorokhobov City Clinical Hospital № 67, Moscow Healthcare DepartmentRussian FederationФГАОУ ВО «Российский университет дружбы народов»РоссияPeoples' Friendship University of RussiaRussian FederationФГБУ «Национальный медицинский исследовательский центр имени В.А. Алмазова» Министерства здравоохранения Российской ФедерацииРоссияAlmazov National Medical Research Centre, Health Ministry of Russian FederationRussian FederationФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет); Университет МонпельеРоссияSechenov University; University of MontpellierRussian FederationФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет); Медицинский Университет Сорбонны; Госпиталь ТенонРоссияSechenov University; Medicine Sorbonne University; Hospital TenonRussian Federation202111112021156639657Copyright © Sluhanchuk E.V., Bitsadze V.O., Khizroeva J.K., Tretyakova M.V., Shkoda A.S., Artyukov O.P., Tsibizova V.I., Mishchenko A.L., Grigorieva K.N., Gris J., Elalamy E., Makatsariya A.D., 20222022Слуханчук Е.В., Бицадзе В.О., Хизроева Д.Х., Третьякова М.В., Шкода А.С., Артюков О.П., Цибизова В.И., Мищенко А.Л., Григорьева К.Н., Гри Ж., Элалами И., Макацария А.Д.Sluhanchuk E.V., Bitsadze V.O., Khizroeva J.K., Tretyakova M.V., Shkoda A.S., Artyukov O.P., Tsibizova V.I., Mishchenko A.L., Grigorieva K.N., Gris J., Elalamy E., Makatsariya A.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gynecology.su/jour/article/view/1138

As shown by numerous studies conducted during the pandemic, the severe course of COVID-19 is accompanied by multiple organ failure. Cytokine storm, hypercoagulation, complement hyperactivation and other arms comprise the overall picture of the pathogenesis of the severe disease course. The frequent diagnosis of multiple microvascular thrombosis in lung, heart, and kidneys, as well as the presence of platelet-fibrin thrombi there and signs of terminal organ damage, suggest a possible involvement of thrombotic microangiopathy (TMA) in the development of multiple organ failure. In this regard, it is especially important to timely diagnose TMA and start pathogenetic therapy. These measures can significantly reduce mortality due to the novel disease. Heparins and direct oral anticoagulants are the mainstay for prevention and treatment of venous thromboembolism in patients with COVID-19, but their effectiveness in the presence of TMA is questionable. It has been proven that anticoagulants use in critically ill patients with COVID-19 for prevention of large vessel thrombosis is effective, but their role in the prevention of microthrombosis is not clear. Here we review the currently available information on thrombotic microangiopathy, as well as a review of literature data describing TMA-like conditions in COVID-19, discuss potential pathophysiology of the condition development and proposed therapeutic approaches.

Как было показано многочисленными исследованиями, проведенными в период пандемии, тяжелое течение COVID-19 сопровождается полиорганной недостаточностью. Цитокиновый шторм, гиперкоагуляция, гиперактивация комплемента и другие звенья гемостаза составляют общую картину патогенеза тяжелого течения заболевания. Частая диагностика множественных тромбозов микрососудистого русла в таких органах как легкие, сердце и почки, а также присутствие тромбоцитарно-фибриновых тромбов в этих органах и признаки их терминального повреждения наводят на мысль о возможном участии тромботической микроангиопатии (ТМА) в развитии полиорганной недостаточности. В этой связи особенно важно своевременно диагностировать ТМА и начинать патогенетическую терапию. Эти мероприятия способны значительно снизить смертность от нового заболевания. Гепарины и прямые пероральные антикоагулянты являются основой профилактики и лечения венозной тромбоэмболии у пациентов с COVID-19, однако их эффективность при наличии ТМА сомнительна. Доказано, что использование антикоагулянтов у тяжелобольных пациентов с COVID-19 для профилактики тромбоза крупных сосудов эффективно, однако их роль в предотвращении микротромбообразования не ясна. В данной статье проводится обзор имеющейся в настоящее время информации о ТМА, а также обзор данных литературы, описывающих ТМА-подобные состояния при COVID-19, обсуждается возможная патофизиология развития состояния и предполагаемые подходы к терапии.

тромботическая микроангиопатияТМАтромботическая тромбоцитопеническая пурпураCOVID-19ADAMTS-13тромбоцитопенияфактор фон Виллебрандаthrombotic microangiopathythrombotic thrombocytopenic purpuraCOVID-19ADAMTS-13thrombocytopeniavon Willebrand factorОбзор выполнен при финансовой поддержке РФФИ в рамках научного проекта РФФИ №20-04-60274.The review was funded by RFBR, project number 20-04-60274.ReferencesZhou F., Yu T., Du R. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–62. https://doi.org/10.1016/S0140-6736(20)30566-3.Zhou F., Yu T., Du R. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–62. https://doi.org/10.1016/S0140-6736(20)30566-3.Ackermann M., Verleden S.E., Kuehnel M. et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120–8. https://doi.org/10.1056/NEJMoa2015432.Ackermann M., Verleden S.E., Kuehnel M. et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120–8. https://doi.org/10.1056/NEJMoa2015432.Cao W., Li T. COVID-19: towards understanding of pathogenesis. Cell Res. 2020;30(5):367–9. https://doi.org/10.1038/s41422-020-0327-4.Cao W., Li T. COVID-19: towards understanding of pathogenesis. Cell Res. 2020;30(5):367–9. https://doi.org/10.1038/s41422-020-0327-4.Zhang Y., Xiao M., Zhang S. et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med. 2020;382(17):e38. https://doi.org/10.1056/NEJMc2007575.Zhang Y., Xiao M., Zhang S. et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med. 2020;382(17):e38. https://doi.org/10.1056/NEJMc2007575.Beyrouti R., Adams M.E., Benjamin L. et al. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry. 2020;91(8):889–91. https://doi.org/10.1136/jnnp2020-323586.Beyrouti R., Adams M.E., Benjamin L. et al. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry. 2020;91(8):889–91. https://doi.org/10.1136/jnnp2020-323586.George J.N., Nester C.M. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014;371(7):654–66. https://doi.org/10.1056/NEJMra1312353.George J.N., Nester C.M. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014;371(7):654–66. https://doi.org/10.1056/NEJMra1312353.Hovinga J.A.K., Vesely S.K., Terrell D.R. et al. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2010;115(8):1500–11; quiz 1662. https://doi.org/10.1182/blood-2009-09-243790.Hovinga J.A.K., Vesely S.K., Terrell D.R. et al. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2010;115(8):1500–11; quiz 1662. https://doi.org/10.1182/blood-2009-09-243790.Ridolfi R.L., Bell W.R. Thrombotic thrombocytopenic purpura: report of 25 cases and review of the literature. Medicine (Baltimore). 1981;60(6):413–28.Ridolfi R.L., Bell W.R. Thrombotic thrombocytopenic purpura: report of 25 cases and review of the literature. Medicine (Baltimore). 1981;60(6):413–28.Moschcowitz E. Hyaline thrombosis of the terminal arterioles and capillaries: a hitherto undescribed disease. Proc NY Pathol Soc. 1924;24:21–24.Moschcowitz E. Hyaline thrombosis of the terminal arterioles and capillaries: a hitherto undescribed disease. Proc NY Pathol Soc. 1924;24:21–24.Singer K., Bornstein F.P., Wile S.A. Thrombotic thrombocytopenic purpura: hemorrhagic diathesis with generalized platelet thromboses. Blood. 1947;2(6):542–54.Singer K., Bornstein F.P., Wile S.A. Thrombotic thrombocytopenic purpura: hemorrhagic diathesis with generalized platelet thromboses. Blood. 1947;2(6):542–54.Amorosi E.L., Ultmann J.E. Thrombotic thrombocytopenic purpura: report of 16 cases and review of the literature. Medicine. 1966;45(2):139–60.Amorosi E.L., Ultmann J.E. Thrombotic thrombocytopenic purpura: report of 16 cases and review of the literature. Medicine. 1966;45(2):139–60.Bukowski R.M., Hewlett J.S., Harris J.W. et al. Exchange transfusions in the treatment of thrombotic thrombocytopenic purpura. Semin Hematol. 1976;13(3):21932.Bukowski R.M., Hewlett J.S., Harris J.W. et al. Exchange transfusions in the treatment of thrombotic thrombocytopenic purpura. Semin Hematol. 1976;13(3):21932.Bukowski R.M., King J.W., Hewlett J.S. Plasmapheresis in the treatment of thrombotic thrombocytopenic purpura. Blood. 1977;50(3):413–7.Bukowski R.M., King J.W., Hewlett J.S. Plasmapheresis in the treatment of thrombotic thrombocytopenic purpura. Blood. 1977;50(3):413–7.Byrnes J.J., Khurana M. Treatment of thrombotic thrombocytopenic purpura with plasma. N Engl J Med. 1977;297(25):1386–9. https://doi.org/10.1056/NEJM197712222972507.Byrnes J.J., Khurana M. Treatment of thrombotic thrombocytopenic purpura with plasma. N Engl J Med. 1977;297(25):1386–9. https://doi.org/10.1056/NEJM197712222972507.Moake J.L., Rudy C.K., Troll J.H. et al. Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med. 1982;307(23):1432–5. https://doi.org/10.1056/NEJM198212023072306.Moake J.L., Rudy C.K., Troll J.H. et al. Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med. 1982;307(23):1432–5. https://doi.org/10.1056/NEJM198212023072306.Furlan M., Robles R., Lämmle B. Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood. 1996;87(10):4223–32.Furlan M., Robles R., Lämmle B. Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood. 1996;87(10):4223–32.Furlan M., Robles R., Solenthaler M. et al. Deficient activity of von Willebrand factor–cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura. Blood. 1997;89(9):3097–103.Furlan M., Robles R., Solenthaler M. et al. Deficient activity of von Willebrand factor–cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura. Blood. 1997;89(9):3097–103.Tsai H.M., Lian E.C. Antibodies to von Willebrand factor–cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. 1998;339(22):1585–94. https://doi.org/10.1056/NEJM199811263392203.Tsai H.M., Lian E.C. Antibodies to von Willebrand factor–cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. 1998;339(22):1585–94. https://doi.org/10.1056/NEJM199811263392203.Zheng X., Chung D., Takayama TK. et al. Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura. J Biol Chem. 2001;276(44):41059–63. https://doi.org/10.1074/jbc.C100515200.Zheng X., Chung D., Takayama TK. et al. Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura. J Biol Chem. 2001;276(44):41059–63. https://doi.org/10.1074/jbc.C100515200.Levy G.G., Nichols W.C., Lian E.C. et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 2001;413(6855):488–94. https://doi.org/10.1038/35097008.Levy G.G., Nichols W.C., Lian E.C. et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 2001;413(6855):488–94. https://doi.org/10.1038/35097008.Scheiflinger F., Knöbl P., Trattner B. et al. Nonneutralizing IgM and IgG antibodies to von Willebrand factor–cleaving protease (ADAMTS-13) in a patient with thrombotic thrombocytopenic purpura. Blood. 2003;102(9):3241–3. https://doi.org/10.1182/blood-2003-05-1616.Scheiflinger F., Knöbl P., Trattner B. et al. Nonneutralizing IgM and IgG antibodies to von Willebrand factor–cleaving protease (ADAMTS-13) in a patient with thrombotic thrombocytopenic purpura. Blood. 2003;102(9):3241–3. https://doi.org/10.1182/blood-2003-05-1616.Bianchi V., Robles R., Alberio L. et al. Von Willebrand factor–cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura. Blood. 2002;100(2):710–3. https://doi.org/10.1182/blood2002-02-0344.Bianchi V., Robles R., Alberio L. et al. Von Willebrand factor–cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura. Blood. 2002;100(2):710–3. https://doi.org/10.1182/blood2002-02-0344.Pereira A., Mazzara R., Monteagudo J. et al. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a multivariate analysis of factors predicting the response to plasma exchange. Ann Hematol. 1995;70(6):319–23. https://doi.org/10.1007/BF01696619.Pereira A., Mazzara R., Monteagudo J. et al. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a multivariate analysis of factors predicting the response to plasma exchange. Ann Hematol. 1995;70(6):319–23. https://doi.org/10.1007/BF01696619.Picod A., Provôt F., Coppo P. Therapeutic plasma exchange in thrombotic thrombocytopenic purpura. Presse Med. 2019;48(11 Pt 2):319–27. https://doi.org/10.1016/j.lpm.2019.08.024.Picod A., Provôt F., Coppo P. Therapeutic plasma exchange in thrombotic thrombocytopenic purpura. Presse Med. 2019;48(11 Pt 2):319–27. https://doi.org/10.1016/j.lpm.2019.08.024.Schulman I., Pierce M., Lukens A., Currimbhoy Z. Studies on thrombopoiesis. I. A factor in normal human plasma required for platelet production; chronic thrombocytopenia due to its deficiency. Blood. 1960;16:943–57.Schulman I., Pierce M., Lukens A., Currimbhoy Z. Studies on thrombopoiesis. I. A factor in normal human plasma required for platelet production; chronic thrombocytopenia due to its deficiency. Blood. 1960;16:943–57.Upshaw J.D. Congenital deficiency of a factor in normal plasma that reverses microangiopathic hemolysis and thrombocytopenia. N Engl J Med. 1978;298(24):1350–2. https://doi.org/10.1056/NEJM197806152982407.Upshaw J.D. Congenital deficiency of a factor in normal plasma that reverses microangiopathic hemolysis and thrombocytopenia. N Engl J Med. 1978;298(24):1350–2. https://doi.org/10.1056/NEJM197806152982407.Zheng X.L., Sadler J.E. Pathogenesis of thrombotic microangiopathies. Annu Rev Pathol. 2008;3:249–77. https://doi.org/10.1146/annurev.pathmechdis.3.121806.154311.Zheng X.L., Sadler J.E. Pathogenesis of thrombotic microangiopathies. Annu Rev Pathol. 2008;3:249–77. https://doi.org/10.1146/annurev.pathmechdis.3.121806.154311.Miyata T., Kokame K., Matsumoto M., Fujimura Y. ADAMTS13 activity and genetic mutations in Japan. Haemostaseologie. 2013;33(2):131–7. https://doi.org/10.5482/HAMO-12-11-0017.Miyata T., Kokame K., Matsumoto M., Fujimura Y. ADAMTS13 activity and genetic mutations in Japan. Haemostaseologie. 2013;33(2):131–7. https://doi.org/10.5482/HAMO-12-11-0017.Furlan M., Lämmle B. Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease. Best Pract Res Clin Haematol. 2001;14(2):437–54. https://doi.org/10.1053/beha.2001.0142.Furlan M., Lämmle B. Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease. Best Pract Res Clin Haematol. 2001;14(2):437–54. https://doi.org/10.1053/beha.2001.0142.Veyradier A., Meyer D., Loirat C. Desmopressin, an unexpected link between nocturnal enuresis and inherited thrombotic thrombocytopenic purpura (Upshaw–Schulman syndrome). J Thromb Haemost. 2006;4(3):700–1. https://doi.org/10.1111/j.1538-7836.2005.01768.x.Veyradier A., Meyer D., Loirat C. Desmopressin, an unexpected link between nocturnal enuresis and inherited thrombotic thrombocytopenic purpura (Upshaw–Schulman syndrome). J Thromb Haemost. 2006;4(3):700–1. https://doi.org/10.1111/j.1538-7836.2005.01768.x.Loirat C., Girma J.-P., Desconclois C. et al. Thrombotic thrombocytopenic purpura related to severe ADAMTS13 deficiency in children. Pediatr Nephrol. 2009;24(1):19–29. https://doi.org/10.1007/s00467-008-0863-5.Loirat C., Girma J.-P., Desconclois C. et al. Thrombotic thrombocytopenic purpura related to severe ADAMTS13 deficiency in children. Pediatr Nephrol. 2009;24(1):19–29. https://doi.org/10.1007/s00467-008-0863-5.Furlan M., Robles R., Morselli B. et al. Recovery and half-life of von Willebrand factorcleaving protease after plasma therapy in patients with thrombotic thrombocytopenic purpura. Thromb Haemost. 1999;81(1):8–13.Furlan M., Robles R., Morselli B. et al. Recovery and half-life of von Willebrand factorcleaving protease after plasma therapy in patients with thrombotic thrombocytopenic purpura. Thromb Haemost. 1999;81(1):8–13.Rock G.A., Shumak K.H., Buskard N.A. et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med. 1991;325(6):393–7. https://doi.org/10.1056/NEJM199108083250604.Rock G.A., Shumak K.H., Buskard N.A. et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med. 1991;325(6):393–7. https://doi.org/10.1056/NEJM199108083250604.Scully M., Hunt B.J., Benjamin S. et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158(3):323–35. https://doi.org/10.1111/j.1365-2141.2012.09167.x.Scully M., Hunt B.J., Benjamin S. et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158(3):323–35. https://doi.org/10.1111/j.1365-2141.2012.09167.x.Scully M., Knöbl P., Kentouche K. et al. Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Blood. 2017;130(19):2055–63. https://doi.org/10.1182/blood-2017-06-788026.Scully M., Knöbl P., Kentouche K. et al. Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Blood. 2017;130(19):2055–63. https://doi.org/10.1182/blood-2017-06-788026.Plaimauer B., Hovinga J.A.K., Juno C. et al. Recombinant ADAMTS13 normalizes von Willebrand factor‐cleaving activity in plasma of acquired TTP patients by overriding inhibitory antibodies. J Thromb Haemost. 2011;9(5):936–44. https://doi.org/10.1111/j.1538-7836.2011.04224.x.Plaimauer B., Hovinga J.A.K., Juno C. et al. Recombinant ADAMTS13 normalizes von Willebrand factor‐cleaving activity in plasma of acquired TTP patients by overriding inhibitory antibodies. J Thromb Haemost. 2011;9(5):936–44. https://doi.org/10.1111/j.1538-7836.2011.04224.x.Gasser C., Gautier E., Steck A. et al. Hemolytic-uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia. Schweiz Med Wochenschr. 1955;85(38–39):905–9. [Article in German].Gasser C., Gautier E., Steck A. et al. Hemolytic-uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia. Schweiz Med Wochenschr. 1955;85(38–39):905–9. [Article in German].Kiibel M., Barnard P. The haemolytic-uraemia syndrome: a survey in Southern Africa. S Afr Med J. 1968;42(27):692–8.Kiibel M., Barnard P. The haemolytic-uraemia syndrome: a survey in Southern Africa. S Afr Med J. 1968;42(27):692–8.Karmali M., Petric M., Steele B., Lim C. Sporadic cases of haemolytic-uraemic syndrome associated with faecal cytotoxin and cytotoxin-producing Escherichia coli in stools. Lancet. 1983;321(8325):619–20. https://doi.org/10.1016/s0140-6736(83)91795-6.Karmali M., Petric M., Steele B., Lim C. Sporadic cases of haemolytic-uraemic syndrome associated with faecal cytotoxin and cytotoxin-producing Escherichia coli in stools. Lancet. 1983;321(8325):619–20. https://doi.org/10.1016/s0140-6736(83)91795-6.O'Brien A., Lively T., Chen M. et al. Escherichia coli 0157:H7 strains associated with haemorrhagic colitis in the United States produce a Shigella dysenteriae 1 (Shiga) like cytotoxin. Lancet. 1983;1(8326 Pt 1):702. https://doi.org/10.1016/s0140-6736(83)91987-6.O'Brien A., Lively T., Chen M. et al. Escherichia coli 0157:H7 strains associated with haemorrhagic colitis in the United States produce a Shigella dysenteriae 1 (Shiga) like cytotoxin. Lancet. 1983;1(8326 Pt 1):702. https://doi.org/10.1016/s0140-6736(83)91987-6.Riley L.W., Remis R.S., Helgerson S.D. et al. Hemorrhagic colitis associated with a rare Escherichia coli serotype. N Engl J Med. 1983;308(12):681–5. https://doi.org/10.1056/NEJM198303243081203.Riley L.W., Remis R.S., Helgerson S.D. et al. Hemorrhagic colitis associated with a rare Escherichia coli serotype. N Engl J Med. 1983;308(12):681–5. https://doi.org/10.1056/NEJM198303243081203.Tarr P.I., Gordon C.A., Chandler W.L. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. 2005;365(9464):1073–86. https://doi.org/10.1016/S0140-6736(05)71144-2.Tarr P.I., Gordon C.A., Chandler W.L. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. 2005;365(9464):1073–86. https://doi.org/10.1016/S0140-6736(05)71144-2.Proesmans W. The role of coagulation and fibrinolysis in the pathogenesis of diarrheaassociated hemolytic uremic syndrome. Semin Thromb Hemost. 2001;27(3):201–5. https://doi.org/10.1055/s-2001-15249.Proesmans W. The role of coagulation and fibrinolysis in the pathogenesis of diarrheaassociated hemolytic uremic syndrome. Semin Thromb Hemost. 2001;27(3):201–5. https://doi.org/10.1055/s-2001-15249.Hosler G.A., Cusumano A.M., Hutchins G.M. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are distinct pathologic entities: a review of 56 autopsy cases. Arch Pathol Lab Med. 2003;127(7):834–9. https://doi.org/10.5858/2003-127-834-TTPAHU.Hosler G.A., Cusumano A.M., Hutchins G.M. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are distinct pathologic entities: a review of 56 autopsy cases. Arch Pathol Lab Med. 2003;127(7):834–9. https://doi.org/10.5858/2003-127-834-TTPAHU.Inward C.D., Howie A.J., Fitzpatrick M.M. et al. Renal histopathology in fatal cases of diarrhoea-associated haemolytic uraemic syndrome. British Association for Paediatric Nephrology. Pediatr Nephrol. 1997;11(5):556–9. https://doi.org/10.1007/s004670050337.Inward C.D., Howie A.J., Fitzpatrick M.M. et al. Renal histopathology in fatal cases of diarrhoea-associated haemolytic uraemic syndrome. British Association for Paediatric Nephrology. Pediatr Nephrol. 1997;11(5):556–9. https://doi.org/10.1007/s004670050337.Menne J., Nitschke M., Stingele R. et al. Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104: H4 induced haemolytic uraemic syndrome: case-control study. BMJ. 2012;345;e4565. https://doi.org/10.1136/bmj.e4565.Menne J., Nitschke M., Stingele R. et al. Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104: H4 induced haemolytic uraemic syndrome: case-control study. BMJ. 2012;345;e4565. https://doi.org/10.1136/bmj.e4565.Barnard P., Kibel M. The haemolytic-uraemic syndrome of infancy and childhood. A report of eleven cases. Cent Afr J Med. 1965;11:4–11.Barnard P., Kibel M. The haemolytic-uraemic syndrome of infancy and childhood. A report of eleven cases. Cent Afr J Med. 1965;11:4–11.Kaplan B.S., Chesney R.W., Drummond K.N. Hemolytic uremic syndrome in families. N Engl J Med. 1975;292(21):1090–3. https://doi.org/10.1056/NEJM197505222922102.Kaplan B.S., Chesney R.W., Drummond K.N. Hemolytic uremic syndrome in families. N Engl J Med. 1975;292(21):1090–3. https://doi.org/10.1056/NEJM197505222922102.Kaplan B.S. Hemolytic uremic syndrome with recurrent episodes: an important subset. Clin Nephrol. 1977;8(6):495–8.Kaplan B.S. Hemolytic uremic syndrome with recurrent episodes: an important subset. Clin Nephrol. 1977;8(6):495–8.Thompson R., Winterborn M. Hypocomplementaemia due to a genetic deficiency of beta 1H globulin. Clin Exp Immunol. 1981;46(1):110. https://doi.org/Thompson R., Winterborn M. Hypocomplementaemia due to a genetic deficiency of beta 1H globulin. Clin Exp Immunol. 1981;46(1):110. https://doi.org/Warwicker P., Goodship T.H., Donne R.L. et al. Genetic studies into inherited and sporadic hemolytic uremic syndrome. Kidney Int. 1998;53(4):836–44. https://doi.org/10.1111/j.1523-1755.1998.00824.x.Warwicker P., Goodship T.H., Donne R.L. et al. Genetic studies into inherited and sporadic hemolytic uremic syndrome. Kidney Int. 1998;53(4):836–44. https://doi.org/10.1111/j.1523-1755.1998.00824.x.Legendre C., Licht C., Muus P. et al. Terminal complement inhibitor eculizumab in atypical hemolytic–uremic syndrome. N Engl J Med. 2013;368(23):2169–81. https://doi.org/10.1056/NEJMoa1208981.Legendre C., Licht C., Muus P. et al. Terminal complement inhibitor eculizumab in atypical hemolytic–uremic syndrome. N Engl J Med. 2013;368(23):2169–81. https://doi.org/10.1056/NEJMoa1208981.Noris M., Caprioli J., Bresin E. et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5(10):1844–59. https://doi.org/10.2215/CJN.02210310.Noris M., Caprioli J., Bresin E. et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5(10):1844–59. https://doi.org/10.2215/CJN.02210310.Lemaire M., Frémeaux-Bacchi V., Schaefer F. et al. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet. 2013;45(5):531–6. https://doi.org/10.1038/ng.2590.Lemaire M., Frémeaux-Bacchi V., Schaefer F. et al. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet. 2013;45(5):531–6. https://doi.org/10.1038/ng.2590.Fremeaux-Bacchi V., Fakhouri F., Garnier A. et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol. 2013;8(4):554–62. https://doi.org/10.2215/CJN.04760512.Fremeaux-Bacchi V., Fakhouri F., Garnier A. et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol. 2013;8(4):554–62. https://doi.org/10.2215/CJN.04760512.Fakhouri F., Roumenina L., Provot F. et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol. 2010;21(5):859–67. https://doi.org/10.1681/ASN.2009070706.Fakhouri F., Roumenina L., Provot F. et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol. 2010;21(5):859–67. https://doi.org/10.1681/ASN.2009070706.Taylor C.M., Machin S., Wigmore S.J., Goodship T.H.; a working party from the Renal Association, the British Committee for Standards in Haematology and the British Transplantation Society. Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom. Br J Haematol. 2010;148(1):37–47. https://doi.org/10.1111/j.1365-2141.2009.07916.x.Taylor C.M., Machin S., Wigmore S.J., Goodship T.H.; a working party from the Renal Association, the British Committee for Standards in Haematology and the British Transplantation Society. Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom. Br J Haematol. 2010;148(1):37–47. https://doi.org/10.1111/j.1365-2141.2009.07916.x.Noris M., Remuzzi G. Managing and preventing atypical hemolytic uremic syndrome recurrence after kidney transplantation. Curr Opin Nephrol Hypertens. 2013;22(6):704–12. https://doi.org/10.1097/MNH.0b013e328365b3fe.Noris M., Remuzzi G. Managing and preventing atypical hemolytic uremic syndrome recurrence after kidney transplantation. Curr Opin Nephrol Hypertens. 2013;22(6):704–12. https://doi.org/10.1097/MNH.0b013e328365b3fe.Sack G.H., Levin J., Bell W.R. Trousseau's syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. Medicine (Baltimore). 1977;56(1):1–37.Sack G.H., Levin J., Bell W.R. Trousseau's syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. Medicine (Baltimore). 1977;56(1):1–37.Elliott M.A., Letendre L., Gastineau D.A. et al. Cancer‐associated microangiopathic hemolytic anemia with thrombocytopenia: an important diagnostic consideration. Eur J Haematol. 2010;85(1):43–50. https://doi.org/10.1111/j.1600-0609.2010.01448.x.Elliott M.A., Letendre L., Gastineau D.A. et al. Cancer‐associated microangiopathic hemolytic anemia with thrombocytopenia: an important diagnostic consideration. Eur J Haematol. 2010;85(1):43–50. https://doi.org/10.1111/j.1600-0609.2010.01448.x.Domingo-Claros A., Larriba I., Rozman M. et al. Acute erythroid neoplastic proliferations. A biological study based on 62 patients. Haematologica. 2002;87(2):148–53.Domingo-Claros A., Larriba I., Rozman M. et al. Acute erythroid neoplastic proliferations. A biological study based on 62 patients. Haematologica. 2002;87(2):148–53.Zheng X.L., Kaufman R.M., Goodnough L.T., Sadler J.E. Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood. 2004;103(11):4043–9. https://doi.org/10.1182/blood-2003-11-4035.Zheng X.L., Kaufman R.M., Goodnough L.T., Sadler J.E. Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood. 2004;103(11):4043–9. https://doi.org/10.1182/blood-2003-11-4035.Hyseni A., Kemperman H., de Lange D.W. et al. Active von Willebrand factor predicts 28-day mortality in patients with systemic inflammatory response syndrome. Blood. 2014;123(14):2153–6. https://doi.org/10.1182/blood-2013-08-508093.Hyseni A., Kemperman H., de Lange D.W. et al. Active von Willebrand factor predicts 28-day mortality in patients with systemic inflammatory response syndrome. Blood. 2014;123(14):2153–6. https://doi.org/10.1182/blood-2013-08-508093.Kerchberger V.E., Ware L.B. The role of circulating cell-free hemoglobin in sepsisassociated acute kidney injury. Semin Nephrol. 2020;40(2):148–59. https://doi.org/10.1016/j.semnephrol.2020.01.006.Kerchberger V.E., Ware L.B. The role of circulating cell-free hemoglobin in sepsisassociated acute kidney injury. Semin Nephrol. 2020;40(2):148–59. https://doi.org/10.1016/j.semnephrol.2020.01.006.Martin K., Borgel D., Lerolle N. et al. Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsisinduced organ failure. Crit Care Med. 2007;35(10):2375–82. https://doi.org/10.1097/01.ccm.0000284508.05247.b3.Martin K., Borgel D., Lerolle N. et al. Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsisinduced organ failure. Crit Care Med. 2007;35(10):2375–82. https://doi.org/10.1097/01.ccm.0000284508.05247.b3.Cao W., Krishnaswamy S., Camire R.M. et al. Factor VIII accelerates proteolytic cleavage of von Willebrand factor by ADAMTS13. Proc Natl Acad Sci U S A. 2008;105(21):7416–21. https://doi.org/10.1073/pnas.0801735105.Cao W., Krishnaswamy S., Camire R.M. et al. Factor VIII accelerates proteolytic cleavage of von Willebrand factor by ADAMTS13. Proc Natl Acad Sci U S A. 2008;105(21):7416–21. https://doi.org/10.1073/pnas.0801735105.Mikes B., Sinkovits G., Farkas P. et al. Elevated plasma neutrophil elastase concentration is associated with disease activity in patients with thrombotic thrombocytopenic purpura. Thromb Res. 2014;133(4):616–21. https://doi.org/10.1016/j.thromres.2014.01.034.Mikes B., Sinkovits G., Farkas P. et al. Elevated plasma neutrophil elastase concentration is associated with disease activity in patients with thrombotic thrombocytopenic purpura. Thromb Res. 2014;133(4):616–21. https://doi.org/10.1016/j.thromres.2014.01.034.Crawley J.T., Lam J.K., Rance J.B. et al. Proteolytic inactivation of ADAMTS13 by thrombin and plasmin. Blood. 2005;105(3):1085–93. https://doi.org/10.1182/blood-2004-03-1101.Crawley J.T., Lam J.K., Rance J.B. et al. Proteolytic inactivation of ADAMTS13 by thrombin and plasmin. Blood. 2005;105(3):1085–93. https://doi.org/10.1182/blood-2004-03-1101.Chen J., Fu X., Wang Y. et al. Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13. Blood. 2010;115(3):706–12. https://doi.org/10.1182/blood-2009-03-213967.Chen J., Fu X., Wang Y. et al. Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13. Blood. 2010;115(3):706–12. https://doi.org/10.1182/blood-2009-03-213967.Lopez-Dee Z., Pidcock K., Gutierrez L.S. Thrombospondin-1: multiple paths to inflammation. Mediators Inflamm. 2011;2011. https://doi.org/10.1155/2011/296069.Lopez-Dee Z., Pidcock K., Gutierrez L.S. Thrombospondin-1: multiple paths to inflammation. Mediators Inflamm. 2011;2011. https://doi.org/10.1155/2011/296069.Studt J.-D., Hovinga J.A.K., Antoine G. et al. Fatal congenital thrombotic thrombocytopenic purpura with apparent ADAMTS13 inhibitor: in vitro inhibition of ADAMTS13 activity by hemoglobin. Blood. 2005;105(2):542–4. https://doi.org/10.1182/blood-2004-06-2096.Studt J.-D., Hovinga J.A.K., Antoine G. et al. Fatal congenital thrombotic thrombocytopenic purpura with apparent ADAMTS13 inhibitor: in vitro inhibition of ADAMTS13 activity by hemoglobin. Blood. 2005;105(2):542–4. https://doi.org/10.1182/blood-2004-06-2096.Tersteeg C., de Maat S., De Meyer S.F. et al. Plasmin cleavage of von Willebrand factor as an emergency bypass for ADAMTS13 deficiency in thrombotic microangiopathy. Circulation. 2014;129(12):1320–31. https://doi.org/10.1161/CIRCULATIONAHA.113.006727.Tersteeg C., de Maat S., De Meyer S.F. et al. Plasmin cleavage of von Willebrand factor as an emergency bypass for ADAMTS13 deficiency in thrombotic microangiopathy. Circulation. 2014;129(12):1320–31. https://doi.org/10.1161/CIRCULATIONAHA.113.006727.Ono T., Mimuro J., Madoiwa S. et al. Severe secondary deficiency of von Willebrand factor–cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure. Blood. 2006;107(2):528–34. https://doi.org/10.1182/blood-2005-03-1087Ono T., Mimuro J., Madoiwa S. et al. Severe secondary deficiency of von Willebrand factor–cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure. Blood. 2006;107(2):528–34. https://doi.org/10.1182/blood-2005-03-1087Kopic A.N., Hollriegl W., Plaimauer B.et al. Subcutaneous administration of ADAMTS13. US Patent App. 16/567,048; 2020.Kopic A.N., Hollriegl W., Plaimauer B.et al. Subcutaneous administration of ADAMTS13. US Patent App. 16/567,048; 2020.Rossio R., Lotta L.A., Pontiggia S. et al. A novel CD46 mutation in a patient with microangiopathy clinically resembling thrombotic thrombocytopenic purpura and normal ADAMTS13 activity. Haematologica. 2015;100(3):e87–9. https://doi.org/10.3324/haematol.2014.111062.Rossio R., Lotta L.A., Pontiggia S. et al. A novel CD46 mutation in a patient with microangiopathy clinically resembling thrombotic thrombocytopenic purpura and normal ADAMTS13 activity. Haematologica. 2015;100(3):e87–9. https://doi.org/10.3324/haematol.2014.111062.Gianviti A., Tozzi A.E., De Petris L. et al. Risk factors for poor renal prognosis in children with hemolytic uremic syndrome. Pediatr Nephrol. 2003;18(12):1229–35. https://doi.org/10.1007/s00467-003-1262-6.Gianviti A., Tozzi A.E., De Petris L. et al. Risk factors for poor renal prognosis in children with hemolytic uremic syndrome. Pediatr Nephrol. 2003;18(12):1229–35. https://doi.org/10.1007/s00467-003-1262-6.Joseph A., Cointe A., Mariani Kurkdjian P. et al. Shiga toxin-associated hemolytic uremic syndrome: a narrative review. Toxins (Basel). 2020;12(2):67. https://doi.org/10.3390/toxins12020067.Joseph A., Cointe A., Mariani Kurkdjian P. et al. Shiga toxin-associated hemolytic uremic syndrome: a narrative review. Toxins (Basel). 2020;12(2):67. https://doi.org/10.3390/toxins12020067.Magro C., Mulvey J.J., Berlin D. et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res. 2020;220:1–13. https://doi.org/10.1016/j.trsl.2020.04.007.Magro C., Mulvey J.J., Berlin D. et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res. 2020;220:1–13. https://doi.org/10.1016/j.trsl.2020.04.007.Bilgin E., Ertenli A.I. Proposal of a new nomenclature for the underlying pathogenetic mechanism of severe coronavirus disease-19: “inflammatory thrombosis with immune endotheliitis – ITIE”. Rheumatol Int. 2021;41(3):679–80. https://doi.org/10.1007/s00296-020-04768-1.Bilgin E., Ertenli A.I. Proposal of a new nomenclature for the underlying pathogenetic mechanism of severe coronavirus disease-19: “inflammatory thrombosis with immune endotheliitis – ITIE”. Rheumatol Int. 2021;41(3):679–80. https://doi.org/10.1007/s00296-020-04768-1.Meizlish M.L., Pine A.B., Goshua G. et al. Circulating markers of angiogenesis and endotheliopathy in COVID-19. medRxiv. 2020;2020.06.29.20140376. https://doi.org/10.1101/2020.06.29.20140376. Preprint.Meizlish M.L., Pine A.B., Goshua G. et al. Circulating markers of angiogenesis and endotheliopathy in COVID-19. medRxiv. 2020;2020.06.29.20140376. https://doi.org/10.1101/2020.06.29.20140376. Preprint.Teuwen L.-A., Geldhof V., Pasut A., Carmeliet P. COVID-19: the vasculature unleashed. Nat Rev Immunol. 2020;20(7):389–91. https://doi.org/10.1038/s41577-020-0343-0.Teuwen L.-A., Geldhof V., Pasut A., Carmeliet P. COVID-19: the vasculature unleashed. Nat Rev Immunol. 2020;20(7):389–91. https://doi.org/10.1038/s41577-020-0343-0.Mohamed M.M., Lukitsch I., Torres-Ortiz A.E. et al. Acute kidney injury associated with coronavirus disease 2019 in urban New Orleans. Kidney360. 2020;1:614–22. https://doi.org/10.34067/KID.0002652020.Mohamed M.M., Lukitsch I., Torres-Ortiz A.E. et al. Acute kidney injury associated with coronavirus disease 2019 in urban New Orleans. Kidney360. 2020;1:614–22. https://doi.org/10.34067/KID.0002652020.Su H., Yang M., Wan C. et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int. 2020;98(1):219–27. https://doi.org/10.1016/j.kint.2020.04.003Su H., Yang M., Wan C. et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int. 2020;98(1):219–27. https://doi.org/10.1016/j.kint.2020.04.003Fox S.E., Akmatbekov A., Harbert J.L. et al. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med. 2020;8(7):681–6. https://doi.org/10.1016/S2213-2600(20)30243-5.Fox S.E., Akmatbekov A., Harbert J.L. et al. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med. 2020;8(7):681–6. https://doi.org/10.1016/S2213-2600(20)30243-5.Carsana L., Sonzogni A., Nasr A. et al. Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study. Lancet Infec Dis. 2020;20(10):1135–40. https://doi.org/10.1016/S1473-3099(20)30434-5.Carsana L., Sonzogni A., Nasr A. et al. Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study. Lancet Infec Dis. 2020;20(10):1135–40. https://doi.org/10.1016/S1473-3099(20)30434-5.Rapkiewicz A.V., Mai X., Carsons S.E. et al. Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: a case series. EClinicalMedicine. 2020;24:100434. https://doi.org/10.1016/j.eclinm.2020.100434.Rapkiewicz A.V., Mai X., Carsons S.E. et al. Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: a case series. EClinicalMedicine. 2020;24:100434. https://doi.org/10.1016/j.eclinm.2020.100434.Menter T., Haslbauer J.D., Nienhold R. et al. Postmortem examination of COVID‐19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology. 2020;77(2):198–209. https://doi.org/10.1111/his.14134.Menter T., Haslbauer J.D., Nienhold R. et al. Postmortem examination of COVID‐19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology. 2020;77(2):198–209. https://doi.org/10.1111/his.14134.Jhaveri K.D., Meir L.R., Chang B.S.F. et al. Thrombotic microangiopathy in a patient with COVID-19. Kidney Int. 2020;98(2):509–12. https://doi.org/10.1016/j.kint.2020.05.025.Jhaveri K.D., Meir L.R., Chang B.S.F. et al. Thrombotic microangiopathy in a patient with COVID-19. Kidney Int. 2020;98(2):509–12. https://doi.org/10.1016/j.kint.2020.05.025.Sharma P., Uppal N.N., Wanchoo R. et al. COVID-19–associated kidney injury: a case series of kidney biopsy findings. J Am Soc Nephrol. 2020;31(9):1948–58. https://doi.org/10.1681/ASN.2020050699.Sharma P., Uppal N.N., Wanchoo R. et al. COVID-19–associated kidney injury: a case series of kidney biopsy findings. J Am Soc Nephrol. 2020;31(9):1948–58. https://doi.org/10.1681/ASN.2020050699.da Silva R.L. Viral-associated thrombotic microangiopathies. Hematol Oncol Stem Cell Ther. 2011;4(2):51–9. https://doi.org/10.5144/1658-3876.2011.51.da Silva R.L. Viral-associated thrombotic microangiopathies. Hematol Oncol Stem Cell Ther. 2011;4(2):51–9. https://doi.org/10.5144/1658-3876.2011.51.Hindilerden F., Yonal-Hindilerden I., Akar E., Kart-Yasar K. Covid-19 associated autoimmune thrombotic thrombocytopenic purpura: report of a case. Thromb Res. 2020;195:136–8. https://doi.org/10.1016/j.thromres.2020.07.005.Hindilerden F., Yonal-Hindilerden I., Akar E., Kart-Yasar K. Covid-19 associated autoimmune thrombotic thrombocytopenic purpura: report of a case. Thromb Res. 2020;195:136–8. https://doi.org/10.1016/j.thromres.2020.07.005.Capecchi M., Mocellin C., Abbruzzese C. et al. Dramatic presentation of acquired thombotic thrombocytopenic purpura associated with COVID-19. Haematologica. 2020;105(10):e540. https://doi.org/10.3324/haematol.2020.262345.Capecchi M., Mocellin C., Abbruzzese C. et al. Dramatic presentation of acquired thombotic thrombocytopenic purpura associated with COVID-19. Haematologica. 2020;105(10):e540. https://doi.org/10.3324/haematol.2020.262345.Varga Z., Flammer A.J., Steiger P. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417–18. https://doi.org/10.1016/S0140-6736(20)30937-5.Varga Z., Flammer A.J., Steiger P. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417–18. https://doi.org/10.1016/S0140-6736(20)30937-5.Nicholson P., Alshafai L., Krings T. Neuroimaging findings in patients with COVID-19. AJNR Am J Neuroradiol. 2020;41(8):1380–3. https://doi.org/10.3174/ajnr.A6630.Nicholson P., Alshafai L., Krings T. Neuroimaging findings in patients with COVID-19. AJNR Am J Neuroradiol. 2020;41(8):1380–3. https://doi.org/10.3174/ajnr.A6630.Bentley M.J., Lehman C.M., Blaylock R.C. et al. The utility of patient characteristics in predicting severe ADAMTS13 deficiency and response to plasma exchange. Transfusion. 2010;50(8):1654–64. https://doi.org/10.1111/j.1537-2995.2010.02653.x.Bentley M.J., Lehman C.M., Blaylock R.C. et al. The utility of patient characteristics in predicting severe ADAMTS13 deficiency and response to plasma exchange. Transfusion. 2010;50(8):1654–64. https://doi.org/10.1111/j.1537-2995.2010.02653.x.Coppo P., Schwarzinger M., Buffet M. et al. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PLoS One. 2010;5(4):e10208. https://doi.org/10.1371/journal.pone.0010208.Coppo P., Schwarzinger M., Buffet M. et al. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PLoS One. 2010;5(4):e10208. https://doi.org/10.1371/journal.pone.0010208.Bendapudi P.K., Hurwitz S., Fry A. et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol. 2017;4(4):e157–e164. https://doi.org/10.1016/S2352-3026(17)30026-1.Bendapudi P.K., Hurwitz S., Fry A. et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol. 2017;4(4):e157–e164. https://doi.org/10.1016/S2352-3026(17)30026-1.Brocklebank V., Wood K.M., Kavanagh D. Thrombotic microangiopathy and the kidney. Clin J Am Soc Nephrol. 2018;13(2):300–17. https://doi.org/10.2215/CJN.00620117.Brocklebank V., Wood K.M., Kavanagh D. Thrombotic microangiopathy and the kidney. Clin J Am Soc Nephrol. 2018;13(2):300–17. https://doi.org/10.2215/CJN.00620117.Sciascia S., Yazdany J., Dall'Era M. et al. Anticoagulation in patients with concomitant lupus nephritis and thrombotic microangiopathy: a multicentre cohort study. Ann Rheum Dis. 2018;78(7):1014–6. https://doi.org/10.1136/annrheumdis-2018-214559.Sciascia S., Yazdany J., Dall'Era M. et al. Anticoagulation in patients with concomitant lupus nephritis and thrombotic microangiopathy: a multicentre cohort study. Ann Rheum Dis. 2018;78(7):1014–6. https://doi.org/10.1136/annrheumdis-2018-214559.Go R.S., Winters J.L., Leung N. et al. Thrombotic microangiopathy care pathway: a consensus statement for the Mayo clinic complement alternative Pathway-Thrombotic microangiopathy (CAP-TMA) Disease-Oriented group. Mayo Clin Proc. 2016;91(9):1189–211. https://doi.org/10.1016/j.mayocp.2016.05.015.Go R.S., Winters J.L., Leung N. et al. Thrombotic microangiopathy care pathway: a consensus statement for the Mayo clinic complement alternative Pathway-Thrombotic microangiopathy (CAP-TMA) Disease-Oriented group. Mayo Clin Proc. 2016;91(9):1189–211. https://doi.org/10.1016/j.mayocp.2016.05.015.Rico-Mesa J.S., Rosas D., Ahmadian-Tehrani A. et al. The role of anticoagulation in COVID-19-induced hypercoagulability. Curr Cardiol Rep. 2020;22(7):53. https://doi.org/10.1007/s11886-020-01328-8.Rico-Mesa J.S., Rosas D., Ahmadian-Tehrani A. et al. The role of anticoagulation in COVID-19-induced hypercoagulability. Curr Cardiol Rep. 2020;22(7):53. https://doi.org/10.1007/s11886-020-01328-8.Bell W.R., Braine H.G., Ness P.M., Kickler T.S. Improved survival in thrombotic thrombocytopenic purpura–hemolytic uremic syndrome: clinical experience in 108 patients. N Engl J Med. 1991;325(6):398–403. https://doi.org/10.1056/NEJM199108083250605.Bell W.R., Braine H.G., Ness P.M., Kickler T.S. Improved survival in thrombotic thrombocytopenic purpura–hemolytic uremic syndrome: clinical experience in 108 patients. N Engl J Med. 1991;325(6):398–403. https://doi.org/10.1056/NEJM199108083250605.Dane K., Chaturvedi S. Beyond plasma exchange: novel therapies for thrombotic thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program. 2018;2018(1):539–47. https://doi.org/10.1182/asheducation-2018.1.539.Dane K., Chaturvedi S. Beyond plasma exchange: novel therapies for thrombotic thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program. 2018;2018(1):539–47. https://doi.org/10.1182/asheducation-2018.1.539.Zielińska K.A., Van Moortel L., Opdenakker G. et al. Endothelial response to glucocorticoids in inflammatory diseases. Front Immunol. 2016;7:592. https://doi.org/10.3389/fimmu.2016.00592.Zielińska K.A., Van Moortel L., Opdenakker G. et al. Endothelial response to glucocorticoids in inflammatory diseases. Front Immunol. 2016;7:592. https://doi.org/10.3389/fimmu.2016.00592.Weiler J., Packard B. Methylprednisolone inhibits the alternative and amplification pathways of complement. Infect Immun. 1982;38(1):122–6. https://doi.org/10.1128/iai.38.1.122-126.1982.Weiler J., Packard B. Methylprednisolone inhibits the alternative and amplification pathways of complement. Infect Immun. 1982;38(1):122–6. https://doi.org/10.1128/iai.38.1.122-126.1982.Limbourg F.P., Huang Z., Plumier J.-C. et al. Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids. J Clin Invest. 2002;110(11):1729–38. https://doi.org/10.1172/JCI15481.Limbourg F.P., Huang Z., Plumier J.-C. et al. Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids. J Clin Invest. 2002;110(11):1729–38. https://doi.org/10.1172/JCI15481.Ruan Q., Yang K., Wang W. et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846–8. https://doi.org/10.1007/s00134-020-05991-x.Ruan Q., Yang K., Wang W. et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846–8. https://doi.org/10.1007/s00134-020-05991-x.RECOVERY Collaborative Group; Horby P., Lim W.S., Emberson J.R. et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693–704. https://doi.org/10.1056/NEJMoa2021436.RECOVERY Collaborative Group; Horby P., Lim W.S., Emberson J.R. et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693–704. https://doi.org/10.1056/NEJMoa2021436.Corral-Gudino L., Bahamonde A., Arnaiz-Revillas F. et al. GLUCOCOVID: a controlled trial of methylprednisolone in adults hospitalized with COVID-19 pneumonia. medRxiv. June 18, 2020. Preprint. https://doi.org/10.1101/2020.06.17.20133579.Corral-Gudino L., Bahamonde A., Arnaiz-Revillas F. et al. GLUCOCOVID: a controlled trial of methylprednisolone in adults hospitalized with COVID-19 pneumonia. medRxiv. June 18, 2020. Preprint. https://doi.org/10.1101/2020.06.17.20133579.Zaki A.M., van Boheemen S., Bestebroer T.M. et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367(19):1814–20. https://doi.org/10.1056/NEJMoa1211721.Zaki A.M., van Boheemen S., Bestebroer T.M. et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367(19):1814–20. https://doi.org/10.1056/NEJMoa1211721.Ohta R., Torii Y., Imai M. et al. Serum concentrations of complement anaphylatoxins and proinflammatory mediators in patients with 2009 H1N1 influenza. Microbiol Immunol. 2011;55(3):191–8. https://doi.org/10.1111/j.1348-0421.2011.00309.x.Ohta R., Torii Y., Imai M. et al. Serum concentrations of complement anaphylatoxins and proinflammatory mediators in patients with 2009 H1N1 influenza. Microbiol Immunol. 2011;55(3):191–8. https://doi.org/10.1111/j.1348-0421.2011.00309.x.Jiang Y., Zhao G., Song N. et al. Blockade of the C5a–C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV. Emerg Microbes Infect. 2018;7(1):1–12. https://doi.org/10.1038/s41426-018-0063-8.Jiang Y., Zhao G., Song N. et al. Blockade of the C5a–C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV. Emerg Microbes Infect. 2018;7(1):1–12. https://doi.org/10.1038/s41426-018-0063-8.O'Brien K.B., Morrison T.E., Dundore D.Y. et al. A protective role for complement C3 protein during pandemic 2009 H1N1 and H5N1 influenza A virus infection. PLoS One. 2011;6(3):e17377. https://doi.org/10.1371/journal.pone.0017377.O'Brien K.B., Morrison T.E., Dundore D.Y. et al. A protective role for complement C3 protein during pandemic 2009 H1N1 and H5N1 influenza A virus infection. PLoS One. 2011;6(3):e17377. https://doi.org/10.1371/journal.pone.0017377.Sun S., Zhao G., Liu C. et al. Inhibition of complement activation alleviates acute lung injury induced by highly pathogenic avian influenza H5N1 virus infection. Am J Respir Cell Mol Biol. 2013;49(2):221–30. https://doi.org/10.1165/rcmb.2012-0428OC.Sun S., Zhao G., Liu C. et al. Inhibition of complement activation alleviates acute lung injury induced by highly pathogenic avian influenza H5N1 virus infection. Am J Respir Cell Mol Biol. 2013;49(2):221–30. https://doi.org/10.1165/rcmb.2012-0428OC.Gralinski L.E., Sheahan T.P., Morrison T.E. et al. Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. mBio. 2018;9(5):e01753–18. https://doi.org/10.1128/mBio.01753-18.Gralinski L.E., Sheahan T.P., Morrison T.E. et al. Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. mBio. 2018;9(5):e01753–18. https://doi.org/10.1128/mBio.01753-18.Stoermer K.A., Morrison T.E. Complement and viral pathogenesis. Virology. 2011;411(2):362–73. https://doi.org/10.1016/j.virol.2010.12.045.Stoermer K.A., Morrison T.E. Complement and viral pathogenesis. Virology. 2011;411(2):362–73. https://doi.org/10.1016/j.virol.2010.12.045.Diurno F., Numis F., Porta G. et al. Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience. Eur Rev Med Pharmacol Sci. 2020;24(7):4040–7. https://doi.org/10.26355/eurrev_202004_20875.Diurno F., Numis F., Porta G. et al. Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience. Eur Rev Med Pharmacol Sci. 2020;24(7):4040–7. https://doi.org/10.26355/eurrev_202004_20875.Home. ClinicalTrials.gov. Available at: https://clinicaltrials.gov.Home. ClinicalTrials.gov. Available at: https://clinicaltrials.gov.Mastaglio S., Ruggeri A., Risitano A.M. et al. The first case of COVID-19 treated with the complement C3 inhibitor AMY-101. Clin Immunol. 2020;215:108450. https://doi.org/10.1016/j.clim.2020.108450.Mastaglio S., Ruggeri A., Risitano A.M. et al. The first case of COVID-19 treated with the complement C3 inhibitor AMY-101. Clin Immunol. 2020;215:108450. https://doi.org/10.1016/j.clim.2020.108450.Winters J.L. Plasma exchange in thrombotic microangiopathies (TMAs) other than thrombotic thrombocytopenic purpura (TTP). Hematology Am Soc Hematol Educ Program. 2017;2017(1):632–8. https://doi.org/10.1182/asheducation-2017.1.632.Winters J.L. Plasma exchange in thrombotic microangiopathies (TMAs) other than thrombotic thrombocytopenic purpura (TTP). Hematology Am Soc Hematol Educ Program. 2017;2017(1):632–8. https://doi.org/10.1182/asheducation-2017.1.632.Albiol N., Awol R., Martino R. Autoimmune thrombotic thrombocytopenic purpura (TTP) associated with COVID-19. Ann Hematol. 2020;99(7):1673–4. https://doi.org/10.1007/s00277-020-04097-0.Albiol N., Awol R., Martino R. Autoimmune thrombotic thrombocytopenic purpura (TTP) associated with COVID-19. Ann Hematol. 2020;99(7):1673–4. https://doi.org/10.1007/s00277-020-04097-0.Khamis F., Al-Zakwani I., Al Hashmi S. et al. Therapeutic plasma exchange in adults with severe COVID-19 infection. Int J Infect Dis. 2020;99:214–8. https://doi.org/10.1016/j.ijid.2020.06.064.Khamis F., Al-Zakwani I., Al Hashmi S. et al. Therapeutic plasma exchange in adults with severe COVID-19 infection. Int J Infect Dis. 2020;99:214–8. https://doi.org/10.1016/j.ijid.2020.06.064.Gucyetmez B., Atalan H.K., Sertdemir I. et al. Therapeutic plasma exchange in patients with COVID-19 pneumonia in intensive care unit: a retrospective study. Crit Care. 2020;24(1):492. https://doi.org/10.1186/s13054-020-03215-8.Gucyetmez B., Atalan H.K., Sertdemir I. et al. Therapeutic plasma exchange in patients with COVID-19 pneumonia in intensive care unit: a retrospective study. Crit Care. 2020;24(1):492. https://doi.org/10.1186/s13054-020-03215-8.Wang Y., Huo P., Dai R. et al. Convalescent plasma may be a possible treatment for COVID-19: a systematic review. Int Immunopharmacol. 2021;91:107262. https://doi.org/10.1016/j.intimp.2020.107262.Wang Y., Huo P., Dai R. et al. Convalescent plasma may be a possible treatment for COVID-19: a systematic review. Int Immunopharmacol. 2021;91:107262. https://doi.org/10.1016/j.intimp.2020.107262.Casadevall A., Joyner M.J., Pirofski L.-A. A randomized trial of convalescent plasma for COVID-19 – potentially hopeful signals. JAMA. 2020;324(5):455–7. https://doi.org/10.1001/jama.2020.10218.Casadevall A., Joyner M.J., Pirofski L.-A. A randomized trial of convalescent plasma for COVID-19 – potentially hopeful signals. JAMA. 2020;324(5):455–7. https://doi.org/10.1001/jama.2020.10218.Rojas M., Rodríguez Y., Monsalve D.M. et al. Convalescent plasma in Covid-19: Possible mechanisms of action. Autoimmun Rev. 2020;19(7):102554. https://doi.org/10.1016/j.autrev.2020.102554.Rojas M., Rodríguez Y., Monsalve D.M. et al. Convalescent plasma in Covid-19: Possible mechanisms of action. Autoimmun Rev. 2020;19(7):102554. https://doi.org/10.1016/j.autrev.2020.102554.Guilpain P., Le Bihan C., Foulongne V. et al. Rituximab for granulomatosis with polyangiitis in the pandemic of covid-19: lessons from a case with severe pneumonia. Ann Rheum Dis. 2021;80(1):e10. https://doi.org/10.1136/annrheumdis-2020-217549.Guilpain P., Le Bihan C., Foulongne V. et al. Rituximab for granulomatosis with polyangiitis in the pandemic of covid-19: lessons from a case with severe pneumonia. Ann Rheum Dis. 2021;80(1):e10. https://doi.org/10.1136/annrheumdis-2020-217549.Callewaert F., Roodt J., Ulrichts H. et al. Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura. Blood. 2012;120(17):3603–10. https://doi.org/10.1182/blood-2012-04-420943.Callewaert F., Roodt J., Ulrichts H. et al. Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura. Blood. 2012;120(17):3603–10. https://doi.org/10.1182/blood-2012-04-420943.Scully M., Cataland S.R., Peyvandi F. et al. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335–46. https://doi.org/10.1056/NEJMoa1806311.Scully M., Cataland S.R., Peyvandi F. et al. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335–46. https://doi.org/10.1056/NEJMoa1806311.

The authors declare that there are no conflicts of interest present.