key: cord-1001892-hpndf3l9
authors: Rossi, Fabio Henrique
title: Venous thromboembolism in COVID-19 patients
date: 2020-10-16
journal: Jornal vascular brasileiro
DOI: 10.1590/1677-5449.200107
sha: 78e7db8bda163a43137cefb2f9d7d96a268ac4dd
doc_id: 1001892
cord_uid: hpndf3l9

COVID-19 is a potentially serious respiratory disease caused by the SARS-CoV-2 virus that involves an increased risk of venous thromboembolism (VTE). Its pathophysiology is apparently related to an exacerbated inflammatory process and coagulopathy, verified by an increase in D-dimer, fibrinogen, and fibrin degradation products. Occurrence must be monitored, prevented, and treated according to existing recommendations and guidelines. The increased risk of thrombosis, and the association between this phenomenon and the most severe forms of the disease and death have prompted some groups to propose a more aggressive prophylactic and therapeutic approach. However, the risk-benefit profile of this type of conduct has not been defined and cases must be assessed individually, with a multidisciplinary approach. In this study, we review the main studies and evidence available to date on diagnosis, prophylaxis, and treatment of venous thromboembolism in COVID-19 patients.

In addition to alveolar lung injuries and acute respiratory failure, the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has also caused a high prevalence of cardiovascular diseases, in particular venous thromboembolism (VTE). [1] [2] [3] The increased risk appears to be particularly associated with an exacerbated inflammatory reaction and exaggerated production of cytokines, in particular interleukin 6. 4, 5 Coagulopathy is detected in the form of high levels of fibrinogen, D-dimer (DD), and factor VIII, and prolongation of the prothrombin time (PT) and the activated partial thromboplastin time (aPTT), factors which are associated with poor clinical prognosis and death. [6] [7] [8] These disorders predominantly occur in patients with risk factors, such as advanced age, obesity, systemic arterial hypertension, diabetes mellitus, heart diseases, lung diseases, cancer, thrombophilias, prior history of VTE, and other comorbidities, but they can also occur in children and younger people, which suggests that there is a genetic component involved. It should also be remembered that immobilization, dehydration, and the need for mechanical ventilation are factors that can contribute to the high prevalence. Prevalence rates during the different phases of the disease have not yet been fully defined; however, it has been observed that in the more severe forms, particularly in patients admitted to intensive care units (ICU), there is an elevated risk of thrombopulmonary embolism (TPE). [1] [2] [3] [6] [7] [8] The recommendations presented here are based on international consensuses on prophylaxis and treatment of VTE in patients without COVID-19, 9,10 on editorials, on retrospective studies of cases series, and on expert recommendations and opinions on clinical practice with COVID-19 patients published recently on a fasttrack basis, the majority without peer review. [11] [12] [13] [14] They should therefore be applied on a case-by-case basis by an experienced multidisciplinary team trained in use of these medications and procedures.

Anticoagulant therapy is associated with substantial benefits (reduction of risk of growth of the thrombus and fatal TPE during the acute disease and of recurrent VTE) and complications. Our objective is to provide an objective and practical presentation of recommendations based on current evidence on diagnosis, prophylaxis, and treatment of VTE in COVID-19 patients.

Patients with clinical suspicion of COVID-19, even when treated at home, and especially those who have fever, anorexia, and diarrhea, should be instructed about the importance of hydration, healthy nutrition, and exercising the limbs. If a clinical suspicion of VTE emerges (pain and swelling of lower limbs, chest pain, sudden exacerbation of dyspnea, etc.), the patient should be instructed to use telemedicine to consult an angiologist or vascular surgeon and, if necessary, attend a consultation in person. Nowadays, the majority of clinics are equipped with equipment for vascular Doppler ultrasonography (VDUS), which can help with diagnosis. In patients treated at home, there are no indications for requesting routine laboratory tests with the objective of identifying coagulopathy or elevated DD. For inpatients, the majority of authors recommend that these data should be verified periodically, although there are no studies that have investigated the cost-effectiveness of this practice. 3, 4 Diagnosis of VTE using imaging methods can be problematic in these patients while the pandemic is ongoing, because of exhaustion of hospital resources and the risk of contamination of people who are not Covid-positive, particularly ICU patients and the care team. 13, 14 For patients with elevated DD or a high degree of clinical suspicion of TPE and when there is no access to tomography, it has been recommended that bedside tests can be employed. Transthoracic echocardiogram can identify signs of right ventricle overload, which may suggest presence of TPE. Point-of-care VDUS can detect deep venous thrombosis present in the femoropopliteal axis. 13, 14 

Patients who take antithrombotics should be instructed to continue taking them, but should be warned about the risk of drug interactions between the antithrombotics and medications prescribed for COVID-19, in particular antivirals and steroidal and non-steroidal anti-inflammatories. In general, pharmacological VTE prophylaxis is not indicated; however, prophylaxis with low molecular weight heparin (LMWH) can be considered, particularly among patients at increased risk of VTE (Caprini score > 8), [11] [12] [13] [14] as long as they are not at increased risk of bleeding. The preference for LMWH is because of its shorter half-life and fewer drug interactions than direct oral anticoagulants (DOACs). Vitamin K antagonists (VKA) should be avoided because of the difficulty of controlling international normalized ratios (INR), and DOACs should be administered instead whenever possible. However, patients with mechanical heart valves, valvular atrial fibrillation, or antiphospholipid antibody syndrome and also breastfeeding patients should be kept on VKA. 13, 14 The possibility of drug interactions between the different anticoagulants and continuous-use medications and those recommended for treatment of COVID-19 should be considered. Liverpool University maintains an extensive list of possible interactions between medications frequently used for COVID-19 on its website.

There is an elevated risk of VTE in all patients admitted with a confirmed diagnosis or clinical suspicion of COVID-19. All of them should be given pharmacological VTE prophylaxis unless there is an absolute contraindication. 9, 10, 13, 14 For patients who are at increased risk (Caprini score > 8), it is recommended that prophylaxis doses should be increased or doubled and, at hospital discharge, parenteral or oral pharmacological VTE prophylaxis should be maintained for a further 30 days. 13, 14 However, we should emphasize that this practice is not supported by the results of clinical studies and should be adopted on a case-by-case basis, considering the risks and benefits for each patient.

The regular subcutaneous (SC) dose of LMWH is 30 mg 2x/day or 40 mg/day. For obese patients (body mass index [BMI] > 30 kg/m 2 ), Caprini score > 8, and elevated DD (200-3500 ng/ml), consider 60 mg, SC, 2x/day; for patients with renal failure (creatinine clearance < 30 mL/min), consider 5000 UI of unfractionated heparin (UFH), SC, 3x/ day; for patients with a history of heparin-induced thrombocytopenia, consider Fondaparinux, 2.5 to 5 mg, SC, 1x/day. For those with platelet counts < 30,000 or an absolute contraindication against anticoagulation, use intermittent pneumatic compression devices. For patients in a critical state, UFH can be prescribed in cases in which it is considered that there is an increased risk of bleeding and an invasive procedure is necessary. When using UFH, bear in mind the risk of contamination associated with the need to take serial blood samples. LMWH can be used at a dosage of 1 mg/kg 2x/day to protect the care team from the risk of contamination associated with using UFH. Patients in hospital in a serious or critical condition should have prothrombin activity time (PAT), APTT, DD, fibrinogen, and fibrin degradation products measured routinely, since elevation of these markers is associated with worse prognosis and a high prevalence of VTE and death. 3,6,11, [13] [14] [15] [16] [17] [18] [19] [20] [21] Indications for VDUS should be the same as those for patients without COVID-19 and this examination should only be performed if the result will be decisive for choice of therapeutic management. Elevated DD levels should not be the only factor in deciding to use VDUS. [11] [12] [13] [14] Preference should be given to use of portable and wireless ultrasound and the point-of-care technique to reduce the risk of contamination. [11] [12] [13] [14] Postmortem studies have demonstrated a high prevalence of pulmonary microthrombosis in COVID-19-positive patients who die. 15, 16 Apparently, all types of heparin are able to reduce DD levels and mortality. 1, 3, 6, [13] [14] [15] [16] [17] [18] [19] [20] [21] Full-dose anticoagulation can be considered for patients with clinical suspicion of VTE and elevated DD (> 3000 mg/dL) and for those who exhibit accentuated increases in levels, as long as there is no absolute contraindication. 13, 14 Risks and benefits should be considered on a case-by-case basis. This conduct apparently offers benefits in terms of reduced length of stay in the ICU and reduced mortality. Published studies have not reported an increased risk of hemorrhage associated with this approach; however, it should be remembered that published studies are scarce and the quality of the scientific evidence available is low. 1,3,6,13-21 Any significant clinical change in the progress of COVID-19 patients should be monitored and the hypothesis of VTE and TPE should be considered. 1,3,6,10,13-18,21-24 The availability of hospital resources and the potential for contamination should be evaluated when choosing tests and treatment tactics. Empirical anticoagulation can be considered in the following situations, if supplementary test results are not available: increased DD (> 500 ng/ mL or constant increase on 2 consecutive days); O 2 saturation < 88% at admission and progressive demand for ventilatory support. In these situations, it is considered that the risk of TPE is high. 1, 3, 6, 10, [13] [14] [15] [16] 18, [21] [22] [23] [24] In critical patients, if there are signs suggestive of massive or submassive TPE, sudden exacerbation of hemodynamic parameters or ventilation, a bedside echocardiogram should be assessed and, if signs of right ventricle overload are found, systemic fibrinolysis or pharmacomechanical thrombectomy should be considered, taking into account the risk of bleeding. 1,3,6,10,13-21 For hospitalized patients, in the case of hemodynamic collapse, cardiac shock, or extracorporeal circulatory support (oxygenation by membrane), pharmacomechanical or surgical thrombectomy should be considered. 1,3,6,10,13-21 If there is a clinical or radiological diagnosis of VTE while in hospital, full anticoagulation should be maintained for at least 3 months. 13, 14 At hospital discharge, for patients at high risk of VTE (age ≥75 years; > 60 years and DD > twice the reference value; 40-60 years and DD > twice the reference value and a history of VTE or cancer), with a Caprini score > 8 or an International Medical Prevention Registry on Venous Thromboembolism (IMPROVE-VTE)score > 4, it is recommended that pharmacological VTE prophylaxis be maintained for at least 6 weeks. 9, 10, 13, 14, 22, 23 

After hospital discharge, LMWH or DOAC can be used; DOAC may be preferred because it offers greater therapeutic convenience. The rivaroxaban dose to be given via the oral route (OR) should be 10 mg/day, OR, for 31 to 39 days (dose and indication approved by the Food and Drug Administration [FDA]). 23, 24 VTE occurs frequently in hospitalized patients, particularly among those in a serious condition being treated in an ICU. Studies indicate that SARS-CoV-2 is associated with an exacerbated inflammatory process, coagulopathy, and higher risk of cardiovascular mortality. The high risk of contagion and hemodynamic instability make it difficult to diagnosis and define the true prevalence of VTE in COVID-19. Therefore, definition of specific models for risk stratification, prophylaxis, and treatment of VTE during the pandemic is a real challenge. There is an urgent need for multicenter randomized clinical trials that can provide reliable data to guide conduct and protocols. However, we must not forget that COVID-19 is an emerging, severe, infectious pandemic for which there is not yet a specific treatment. 25 Apparently, VTE is a common complication and is related to the most severe cases and to mortality. Use of LMWH in prophylactic and therapeutic doses has been demonstrating clinical benefits and low risk of hemorrhagic complications. It can therefore be concluded that there is an elevated risk of VTE during the COVID-19 pandemic and that prophylaxis and treatment with heparin in its several different presentations and dosages should be provided aggressively for patients who are not at high risk of hemorrhagic complications. 

A pandemia Covid-19, causada pelo coronavírus SARS-CoV-2, além de poder provocar lesão pulmonar alveolar e falência respiratória aguda, apresenta uma elevada prevalência de doenças cardiovasculares, sobretudo tromboembolismo venoso (TEV) 1-3 . Esse aumento do risco parece estar particularmente associado a reação inflamatória exacerbada e liberação exagerada de citocinas, sobretudo interleucina 6 4,5 . A coagulopatia é verificada pelo aumento dos índices de fibrinogênio, D-dímero (DD), fator VIII e prolongamento do tempo de protrombina (TP) e do tempo de tromboplastina parcial ativada (TTPa), fatores associados a má evolução clínica e óbito [6] [7] [8] .

Esses distúrbios ocorrem sobretudo em pacientes portadores de fatores de risco, como idade avançada, obesidade, hipertensão arterial sistêmica, diabetes mellitus, cardiopatias, pneumopatias, câncer, trombofilias, história prévia de TEV e outras comorbidades, mas também em crianças e indivíduos mais jovens, sugerindo haver um componente genético envolvido. Além disso, a imobilização, desidratação e necessidade de ventilação mecânica são fatores que podem contribuir para a alta prevalência de TEV na COVID-19. Apesar de essa prevalência não estar definida nas diversas fases da doença, tem-se observado que, nas formas mais graves e principalmente nos pacientes internados em unidade de terapia intensiva (UTI), existe elevado risco de tromboembolia pulmonar (TEP) 1-3,6-8 .

As recomendações aqui apresentadas são baseadas em consensos internacionais para a profilaxia e o tratamento de TEV em pacientes não COVID-19 9,10 , em editoriais, estudos retrospectivos de séries de casos e recomendações e opiniões de especialistas publicadas recentemente em regime de urgência, a maioria sem revisão por pares, sobre a prática clínica em pacientes COVID-19 [11] [12] [13] [14] . Dessa forma, devem ser aplicadas de forma individualizada e por equipe multidisciplinar experiente e treinada no manuseio dessas medicações e procedimentos.

A terapia anticoagulante está associada a benefícios substanciais (redução de risco de extensão de trombo e TEP fatal na doença aguda e recorrência de TEV). Nosso objetivo é apresentar, de forma objetiva e prática, recomendações baseadas nas evidências atuais sobre o diagnóstico, profilaxia e tratamento do TEV em pacientes COVID-19.

Pacientes com suspeita clínica de COVID-19, mesmo tratados em regime domiciliar e especialmente aqueles que apresentem febre, anorexia e diarreia, devem ser orientados sobre a importância da hidratação, alimentação saudável e exercício dos membros. Na ocorrência de suspeita clínica de TEV (dor e edema de membros inferiores, dor torácica, piora súbita da dispneia etc.), o paciente deve ser orientado a procurar, via telemedicina, um angiologista ou cirurgião vascular e, caso necessário, realizar consulta presencial. Hoje, a maioria das clínicas é equipada com equipamentos de eco-Doppler vascular (EDV), que pode auxiliar no diagnóstico. Em pacientes tratados em regime domiciliar, não existe indicação para a solicitação de exames laboratoriais de rotina com o objetivo de identificar a presença de coagulopatia ou aumento de DD. Nos pacientes internados, a maioria dos autores recomenda que esses dados sejam checados periodicamente, apesar de não haver estudos que tenham verificado a custo-efetividade de tal prática 3, 4 . Nesses pacientes, o diagnóstico do TEV por métodos de imagem complementares pode ser problemático durante o curso de uma pandemia devido à exaustão dos recursos hospitalares, além do risco de contaminação daqueles não COVID positivo, sobretudo daqueles internados em UTI, e da equipe envolvida no tratamento 13, 14 .

Nos pacientes que apresentam DD elevado ou suspeita clínica elevada de TEP e quando houver dificuldade de acesso a tomografia, tem sido recomendada a realização de exames complementares à beira do leito. O ecocardiograma transtorácico é capaz de identificar sinais de sobrecarga de ventrículo direito, que podem sugerir a presença de TEP. O EDV, realizado pela técnica point-of-care, pode verificar a presença de trombose venosa profunda no eixo fêmoro-poplíteo 13,14 .

Os pacientes que fazem uso de antitrombóticos devem ser orientados a continuar o uso desse medicamento, mas devem ser alertados sobre o risco de interação medicamentosa entre esses e medicamentos prescritos para a COVID-19, sobretudo os antivirais e antiinflamatórios hormonais e não hormonais. De uma forma geral, não existe indicação para a farmacoprofilaxia do TEV; entretanto, a profilaxia com heparina de baixo peso molecular (HBPM) pode ser considerada, sobretudo nos portadores de risco aumentado para TEV (escore de Caprini > 8) [11] [12] [13] [14] , desde que não haja risco aumentado para sangramento. A HBMP deve ser priorizada por apresentar meia vida mais curta e menor interação medicamentosa que os anticoagulantes orais diretos (DOACs). O uso de antagonistas da vitamina K (AVK) deve ser evitado pela dificuldade de controle dos níveis do índice internacional normalizado (INR), devendo-se administrar DOACs em seu lugar sempre que possível. Entretanto, pacientes portadores de válvulas mecânicas cardíacas, fibrilação atrial valvar síndrome do anticorpo antifosfolípide ou pacientes que estejam amamentando devem continuar usando AVK 13, 14 . Deve ser considerada a existência de interação medicamentosa entre os diversos agentes anticoagulantes com os medicamentos de uso contínuo e os recomendados para o tratamento da COVID-19. A universidade de Liverpool disponibiliza em seu site uma extensa lista de possíveis interações entre os medicamentos frequentemente utilizados na COVID-19.

Em todos os pacientes internados com diagnóstico confirmado ou suspeita clínica de COVID-19, existe risco elevado de TEV. Todos devem receber farmacoprofilaxia, caso não haja contraindicação absoluta 9, 10, 13, 14 . Nos pacientes que apresentam risco aumentado (escore de Caprini > 8), recomenda-se o uso de dose aumentada ou dobrada de profilaxia e, na ocasião da alta hospitalar, a extensão da farmacoprofilaxia parenteral ou oral por até 30 dias 13, 14 . Entretanto, devemos enfatizar que essa prática não é fundamentada em estudos clínicos e deve ser aplicada de forma individualizada, considerando os riscos e benefícios em cada caso específico.

A dose regular de HBPM, subcutânea (SC), é de 30 mg 2x/dia ou 40 mg/dia. Para pacientes com obesidade [índice de massa corporal (IMC) > 30 kg/m 2 ), escore de Caprini > 8 e DD elevado (200-3500 ng/mL), considerar 60 mg, SC, 2x/dia; para pacientes com insuficiência renal (Clearence de creatinina < 30 mL/min), considerar heparina não fracionada (HNF) 5000 UI, SC 3x/dia; para paciente com história de trombocitopenia induzida por heparina, considerar Fondaparinux, 2,5 a 5 mg, SC, 1x/dia. Para aqueles com contagem de plaquetas < 30.000 ou contraindicação absoluta para anticoagulação, usar dispositivos de compressão pneumática intermitente. Para pacientes em estado crítico, a HNF pode ser indicada nos casos em que se considera haver risco aumentado de sangramento e necessidade de procedimento invasivo. No uso da HNF, considerar o risco de contaminação associado à necessidade de coleta de amostra sanguínea seriada. A HBPM pode ser usada na dosagem de 1 mg/kg 2x/dia para proteger a equipe do risco de contaminação, associada ao uso de HNF. Pacientes internados em estado grave ou crítico devem ter os níveis de tempo de atividade da protrombina (TAP), TTPa, DD, fibrinogênio e produto de degradação de fibrina mensurados, rotineiramente, uma vez que a elevação desses marcadores está associada a pior prognóstico e a alta prevalência de TEV e óbito 3, 6, 11, [13] [14] [15] [16] [17] [18] [19] [20] [21] .

As indicações para a realização de EDV devem ser as mesmas daquelas para pacientes não COVID-19, e esse exame só deve ser realizado se seu resultado for decisivo para a determinação da conduta terapêutica. O nível aumentado do DD não deve ser o único fator para a realização do EDV [11] [12] [13] [14] . Deve ser dada preferência a equipamento de ultrassom portátil e sem fio e a técnica point-of-care para diminuir os riscos de contaminação [11] [12] [13] [14] . Estudos necroscópicos vêm demonstrando alta prevalência de microtrombose pulmonar em pacientes COVID-19 positivo que evoluíram a óbito 15, 16 . Aparentemente, todas as heparinas são capazes de diminuir os níveis de DD e a mortalidade 1,3,6,13-21 .

Pode-se considerar a anticoagulação em dose plena para os pacientes com suspeita clínica de TEV e dosagem elevada de DD (> 3000 mg/dL) e para aqueles que evoluam com aumento acentuado dos valores, desde que não haja contraindicação absoluta para tal 13, 14 . Os riscos e benefícios devem ser considerados individualmente. Essa conduta aparentemente é benéfica ao reduzir o tempo de UTI e mortalidade. Os estudos publicados não verificaram aumento do risco de hemorragia com esse tipo de conduta; entretanto, deve-se levar em conta a escassez de estudos publicados e a baixa qualidade da evidência científica 1,3,6,13-21 . Qualquer alteração clínica significativa na evolução do paciente COVID-19 deve ser monitorada e considerada a hipótese de ocorrência de TEV e TEP 1,3,6,10,13-21 . Deve-se avaliar a disponibilidade de recursos hospitalares e o potencial de contaminação na escolha dos exames complementares e da tática terapêutica. A anticoagulação empírica pode ser considerada nas seguintes situações, caso não haja acesso a exames complementares: aumento de DD (> 500 ng/mL ou aumento constante em dois dias consecutivos); saturação de O2 < 88% na admissão e necessidade progressiva de suporte ventilatório. Nessas situações, considera-se que o risco de TEP é alto 1,3,6,10,13-21 . Nos pacientes críticos, se houver sinais sugestivos de TEP maciço ou submaciço, piora súbita dos parâmetros hemodinâmicos ou do padrão ventilatório, deve-se avaliar a indicação de ecocardiograma à beira do leito e, se forem identificados sinais de sobrecarga no ventrículo direito, deve-se considerar a fibrinólise sistêmica ou trombectomia farmacomecânica, considerando-se o risco de sangramento 1,3,6,10,13-21 . Nos pacientes internados, caso haja colapso hemodinâmico, choque cardíaco ou suporte circulatório extracorpóreo (oxigenação por membrana), deve ser considerada a trombectomia farmacomecânica ou cirúrgica 1,3,6,10,13-21 . Se, durante a internação, houver diagnóstico clínico ou radiológico de TEV, deve ser mantida anticoagulação plena por pelo menos 3 meses 13, 14 . Na alta hospitalar, nos pacientes em que for identificado risco alto para TEV (idade ≥75 anos; > 60 anos e DD > duas vezes o valor de referência; 40-60 anos e DD > duas vezes o valor de referência e história de TEV ou câncer), escore de Caprini > 8 ou International Medical Prevention Registry on Venous Thromboembolism (IMPROVE-VTE) > 4, recomenda-se farmacoprofilaxia por pelo menos 6 semanas 9,10,13,14,22,23 .

Após a alta hospitalar, podem ser usados HBPM ou DOAC, e DOACs podem ser preferidos por apresentarem melhor comodidade terapêutica. A dose de rivaroxabana a ser utilizada via oral (VO) deve ser de 10 mg/dia, VO, por 31 a 39 dias [dose e indicação aprovada pela Food and Drug Administration (FDA)] 23, 24 .

O TEV ocorre frequentemente em pacientes hospitalizados, sobretudo naqueles em estado grave e tratados em UTI. Estudos apontam que o SARS-CoV-2 é associado a processo inflamatório exacerbado, coagulopatia e maior risco de mortalidade cardiovascular. O alto risco de contágio e a instabilidade hemodinâmica dificultam o diagnóstico e a definição da real prevalência do TEV na COVID-19. Dessa forma, o estabelecimento de modelos específicos para a estratificação dos riscos, de profilaxia e de tratamento do TEV durante a pandemia representa um verdadeiro desafio. Existe uma necessidade urgente de estudos clínicos, multicêntricos e randomizados, que possam trazer dados confiáveis para nortear condutas e protocolos. Entretanto, devemos considerar que a COVID-19 é uma pandemia infecciosa grave, recente e para a qual não existe, até o momento, um tratamento específico 25 . Aparentemente, o TEV representa uma complicação frequente e relacionada a casos mais graves e óbito. O uso de HBPM em doses profiláticas e terapêuticas vem demonstrando benefício clínico e baixo risco de complicações hemorrágicas. Dessa forma, concluo que existe elevado risco de TEV na pandemia COVID-19 e que a profilaxia e o tratamento com o uso de heparina em suas diversas formas posológicas devem ser realizados de forma agressiva nos pacientes que não apresentem risco elevado de complicações hemorrágicas.

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

Thromboinflammation and the hypercoagulability of COVID-19

Interleukin-6 as a potential biomarker of COVID-19 progression

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

COVID-19 complicated by acute pulmonary embolism

Incidence of thrombotic complications in critically ill ICU patients with COVID-19

American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients

The 40th International Symposium on Intensive Care & Emergency Medicine: Brussels, Belgium

Completion of the Updated Caprini Risk Assessment Model

The versatile heparin in COVID-19

Scientific and Standardization Committee Comunication: clinical guidance on the diagnosis, prevention and treatment of venous thromboembolism in hospitalized patients with COVID-19

Considerations in prophylaxis and treatment of VTE in COVID-19 patients. Illinois: American Venous Forum

Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19

Pulmonary post mortem findings in a large series of COVID-19 cases from Northern

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan

D-dimer is associated with severity of coronavirus disease 2019: a pooled analysis

Anticoagulant treatment is associated with decreased mortality in severe

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

Thromboinflammation and the hypercoagulability of COVID-19

Interleukin-6 as a potential biomarker of COVID-19 progression

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

COVID-19 complicated by acute pulmonary embolism

Incidence of thrombotic complications in critically ill ICU patients with COVID-19

American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients

The 40th International Symposium on Intensive Care & Emergency Medicine: Brussels, Belgium

Completion of the Updated Caprini Risk Assessment Model

The versatile heparin in COVID-19

Scientific and Standardization Committee Comunication: clinical guidance on the diagnosis, prevention and treatment of venous thromboembolism in hospitalized patients with COVID-19

Considerations in prophylaxis and treatment of VTE in COVID-19 patients. Illinois: American Venous Forum

Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19

Pulmonary post mortem findings in a large series of COVID-19 cases from Northern

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in

D-dimer is associated with severity of coronavirus disease 2019: a pooled analysis

Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

Findings of acute pulmonary embolism in COVID-19 patients

Acute Pulmonary Embolism Associated with COVID-19 pneumonia detected by pulmonary CT angiography

Modified IMPROVE VTE Risk score and elevated D-dimer identify a high venous thromboembolism risk in acutely ill medical population for extended thromboprophylaxis

Rivaroxaban for thromboprophylaxis in acutely ill medical patients

Improved benefit risk profile of rivaroxaban in a subpopulation of the MAGELLAN study

A panaceia dos anticoagulantes na infecção pela COVID-19

vascular369@hotmail.com Informações sobre o autor FHR -Doutor e Pós-doutor

Precepetor de Cirurgia Vascular e Endovascular, IDPC; Coordenador, Disciplina de Pós-graduação Tecnologia em Cirurgia Cardiovascular e Endovascular Extracardíaca (IDPC/FMUSP)