ABC | Volume 114, Nº5, May 2020

Viewpoint The novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the outbreak of the viral pneumonia identified for the first time in the Chinese city of Wuhan at the end of 2019. The outbreak has expanded rapidly, affecting 184 countries. The experience acquired in past months identified different clinical presentations with varied severity, ranging from asymptomatic infection to death due to multiple organic dysfunction. The World Health Organization (WHO) has recently defined the complex process of the SARS-CoV-2 infection as novel coronavirus disease 2019 (COVID-19). COVID-19, whose notification grows fast in different countries, currently affects more than one million people worldwide according to the WHO, which has characterized the infection as a pandemic. 1 As of April 29, 2020, Brazil had registered 73,235 confirmed cases of COVID-19 and 5,083 deaths, with a case-fatality rate of 6,9%. 2 Hospitalization is necessary in up to 20% of the patients infected by SARS- CoV-2, and 5% to 10% of them require admission to the intensive care unit because of the need for hemodynamic and/or ventilatory support. 3-7 The mortality rate ranges from 0.8% to 12% depending on the country, and this difference might result from multiple factors, of which the healthcare system structure stands out. 8-11 Patients with the moderate and severe forms of the disease had manifestations mainly of the respiratory system involvement, with clinical findings ranging from mild pneumonia to acute respiratory distress syndrome (ARDS). 7,11-13 Complications usually occur between the 7th and 12th day of disease. 3,14 The most severe clinical manifestation, ARDS, is characterized by hypoxemia, bilateral pulmonary infiltrate, and variable phenotypic presentations, such as ‘normal lung compliance and low potential for lung recruitment’ and ‘low lung compliance and high potential for lung recruitment’. From 20% to 30% of the patients have cardiovascular complications, such as myocardial ischemia, acute coronary syndrome, myocarditis, arrhythmias, heart failure and shock. Kidney failure occurs in 30-50% of critically ill patients infected by SARS-CoV-2, 30% of whom require renal replacement therapy. 14-17 The SARS-CoV-2 enters the cell via the angiotensin- converting enzyme 2 (ACE2) receptor present in the alveoli. The severe form of the infection is characterized by an intense immune-inflammatory response, evidenced by the presence of neutrophils, lymphocytes, monocytes and macrophages.18 Minimally invasive autopsies have revealed diffuse alveolar damage, hyaline membrane formation and interstitial mononuclear inflammatory infiltrate, with microcirculatory thrombosis. 17 High serum levels of pro- inflammatory cytokines (interleukins 1 and 6, tumor necrosis factor and interferon- g ), known as “cytokine storm”, have been reported in those patients. Thrombosis and damage to extrapulmonary organs have been observed without the confirmed presence of the virus in those sites, which led to the assumption that SARS- CoV-2 infection involves intense inflammatory response with a hypercoagulable state and ischemia, aggravated by hypoxemia. 17,19,20 In Brazil, preliminary findings of minimally invasive autopsies performed at the São Paulo Medical School have shown similar results to those from China. 21 When elevated, D-dimer, a product of fibrin degradation, has been associated with a higher mortality rate. 22 Expert opinion, based on clinical experience and analysis of a few descriptive studies, highlights the role of the hypercoagulable state on the pathophysiology of COVID-19, supported by the progressive increase in D-dimer levels as the disease worsens. The phase in which ARDS develops and the radiographic pattern worsens is marked by the significant elevation of D-dimer. The most severe cases develop myocardial injury and disseminated intravascular coagulation (DIC). 23,24 Mailing Address: Gláucia Maria Moraes de Oliveira • Universidade Federal do Rio de Janeiro – Cardiologia - Universidade Federal do Rio de Janeiro Rua Visconde de Pirajá, 330 Sala 1114. Postal Code 21941-901, Rio de Janeiro, RJ – Brazil E-mail: glauciamoraesoliveira@gmail.com Manuscript received April 10, 2020, revised mansucript April 15, 2020, accepted April 15, 2020 Keywords COVID-2019; Betacoronavirus; Catastrophic Illness; Viral, Pneumonia; Pandemics; Coronavirus Infections; Complications, Cardiovasculares; Thrombophilia; Anticoagulants/therapeutic use. DOI: https://doi.org/10.36660/abc.20200308 COVID-19 and Hypercoagulable State: A New Therapeutic Perspective Jorge Henrique Paiter Nascimento, 1 Bruno Ferraz de Oliveira Gomes, 1, 2 Plínio Resende do Carmo Júnior, 1 João Luiz Fernandes Petriz, 2,3 Stephanie Itala Rizk, 4,5 Isabela Bispo Santos da Silva Costa, 6 Marcus Vinicius Guimarães Lacerda, 7 Fernando Bacal, 8 Ludhmila Abrahão Hajjar, 9 Gláucia Maria Moraes de Oliveira 1 Universidade Federal do Rio de Janeiro – Cardiologia, 1 Rio de Janeiro, RJ - Brazil Rede D’Or São Luiz – Cardiologia ,2 Rio de Janeiro, RJ - Brazil Hospital Barra D’Or – Cardiologia, 3 Rio de Janeiro, RJ - Brazil Universidade de São Paulo Instituto do Câncer do Estado de São Paulo, 4 São Paulo, SP - Brazil Universidade de São Paulo Instituto do Coração, 5 São Paulo, SP - Brazil Hospital Sírio-Libanês - Instituto Sírio Libanês de Ensino e Pesquisa, 6 São Paulo, SP - Brazil Fundação de Medicina Tropical Dr Heitor Vieira Dourado, 7 Manaus, AM - Brazil Universidade de São Paulo Faculdade de Medicina Hospital das Clínicas Instituto do Coração, 8 São Paulo, SP - Brazil Intituto de Coração – Cardiopneumologia, 9 São Paulo, SP – Brasil 829