Caracterização da Coagulopatia Associada ao COVID-19 usando Tromboelastometria Rotacional num Estudo Observacional de Coorte Prospetivo: Estudo HemoCov
DOI:
https://doi.org/10.20344/amp.19475Palavras-chave:
COVID-19, Fibrinólise, Perturbações da Coagulação Sanguínea, Tromboelastometria, TromboseResumo
Introdução: A coagulopatia associada à COVID-19 inclui inflamação sistémica e endotelial com desregulação da coagulação relacionada com imunotrombose. O objetivo deste estudo foi caracterizar esta complicação da infecção por SARS-CoV-2 em doentes com infeção COVID-19 moderada a grave.
Métodos: Estudo prospetivo observacional open-label conduzido em doentes com insuficiência respiratória aguda COVID-19 moderada a grave admitidos numa unidade de cuidados intensivos (UCI). Testes da coagulação, incluindo tromboelastometria, testes de bioquímica e variáveis clínicas foram colhidos em pontos de análise predefinidos durante 30 dias de internamento na UCI.
Resultados: Foram incluídos 145 doentes, 73,8% homens, com uma mediana de idade de 68 anos (intervalo interquartílico – IIQ 55 - 74). As comorbilidades mais prevalentes foram hipertensão arterial (63,4%), obesidade (44,1%) e diabetes (22,1%). Na admissão, o simplified acute physiology score II (SAPS II) apresentou uma mediana de 43,5 (11 - 105) e o sequential organ failure assessment (SOFA) de 7,5 (0 - 14). Durante a estadia na UCI, 66,9% dos doentes foram submetidos a ventilação mecânica invasiva e 18,4% a suporte com extracorporeal membrane oxygenation; Eventos trombóticos e hemorrágicos ocorreram em 22,1% e 15,1% dos doentes respetivamente; anticoagulação com heparina esteve presente em 99,2% dos doentes desde precocemente durante a estadia na UCI. A morte ocorreu em 35% dos doentes. Estudos longitudinais revelaram alterações em quase todos os testes da coagulação durante a hospitalização na UCI. O SOFA score, a contagem de linfócitos, alguns parâmetros bioquímicos, inflamatórios e da coagulação, incluindo hipercoagulabilidade e hipofibrinólise observados na tromboelastometria, diferiram significativamente (p < 0,05), entre a admissão e a alta da UCI. A hipercoagulabilidade e a hipofibrinólise persistiram ao longo da hospitalização na ICU, mostrando maior incidência e gravidade nos doentes não sobreviventes.
Conclusão: A coagulopatia associada à COVID-19 é caracterizada por hipercoagulabilidade e hipofibrinólise desde a admissão na UCI, as quais persistiram durante o curso clínico na infeção COVID-19 grave. Estas alterações foram mais pronunciadas nos doentes com maior gravidade e nos não sobreviventes.
Downloads
Referências
Connors JA, Iba T, Gandhi RT. Thrombosis and COVID-19: controversies and (tentative) conclusions. Clin Infect Dis. 2021;73:2294-7.
Magnani HN. Rational for the role of heparin and related gag antithrombotics in COVID-19 infection. Clin Appl Thromb Hemost. 2021;27:1-26.
Thachil J, Juffermans NP, Ranucci M, Connors JM, Warkentin TE, Ortel TL, et al. ISTH DIC subcommittee communication on anticoagulation in COVID-19. J Thromb Haemost. 2020;18:2138-44.
Ramacciotti E, Macedo AS, Biagioni RB, Caffaro RA, Lopes RD, Guerra JC, et al. Evidence-based guidance for the antithrombotic management in patients with coronavirus disease (COVID-19) in 2020. Clin Appl Thromb Hemost. 2020;26:1-8.
Flaczyk A, Rosovsky RP, Reed CT, Bankhead-Kebdall BK, Bittner E, Chang MG. Comparison of published Guidelines for Management of Coagulopathy and Thrombosis in Critically Ill Patients with COVID-19: implications for clinical practice and future investigations. Critical Care. 2020;24:559.
Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfust I, Driggin E, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. JACC state-of-theart-review. J Am Coll Cardiol. 2020;75:2950-73.
Riva G, Nasillo V, Tagliafico E, Trenti T, Comoli P, Luppi M. COVID-19: more than a cytokine strom. Critical Care. 2020;24:549-51.
Zanza C, Racca F, Longhitano Y, Piccioni A, Franceschi F, Artico M, et al. Risk management and treatment of coagulation disorders related to COVID-19 infection. Int J Environ Res Public Health. 2021;18:1268.
Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844-7.
Han H, Yang L, Liu R, Liu F, Wu KL, Li J, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020;58:1116-20.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054-62.
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180:934-43.
Gao Y, Li T, Han M, Li X, Wu D, Xu Y, et al. diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J Med Virol. 2020;92:791-6.
Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021;93:250-6.
Zanza C, RomensKaya T, Manetti C, Franceschi F, La Russa R, Bertozzi G, et al. Cytokine storm in COVID-19 immunopathogenesis and therapy. Medicina. 2022;58:144.
Schulman S, Sholzberg M, Spyropoulos AC, Zarychanski R, Resnick HE, Bradbury CA, et al, on behalf of the International Society on Thrombosis and Haemostasis. ISTH guidelines for antithrombotic treatment in COVID-19. J Thromb Haemost. 2022;20:2214-25.
COVID-19 Treatment Guidelines Panel. Coronavirus disease 2019 (COVID-19) treatment guidelines. National Institutes of Health (NIH). [cited 2023 Mar 11]. Available at: https://www.covid19treatmentguidelines.nih.gov.
Cuker A, Tseng EK, Nieuwlaat R, Angchaisuksiri P, Blair C, Dane K, et al. American Society of Hematology 2021 Guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19. Blood Advances. 2021;5:872-88.
Cuker A, Tseng EK, Nieuwlaat R, Angchaisuksiri P, Blair C, Dane K, et al. American Society of Hematology living Guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: january 22 update on the use of therapeutic-intensity anticoagulation in acutely ill patients. Blood Advances. 2022;6:4915-23.
Kreuziger LB, Sholzberg M, Cushman M. Anticoagulation in hospitalized patients with COVID-19. Blood. 2022;140:809-14.
Barnes GD, Burnett A, Allen A, Ansell J, Blumenstein M, Clark NP, et al. Thromboembolic prevention and anticoagulation therapy during the COVID-19 pandemic: update clinical guidelines from the anticoagulation forum. J Thromb Thrombolysis. 2022;54:197-210.
Von Elm E, Altman DG, Egger M, Pocok SJ, Gotzsche PC, Vandenbroucke JP, for the STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. PLOS Med. 2007;4:e296.
Marshall JC, Murthy S, Diaz SJ and collaborators of WHO Working Group on the Clinical Characterization and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. WHO Working Group on the Clinical Characterization and Management of COVID-19 infection. Lancet Infect Dis. 2020;20:e192-7.
Estcourt L, Birchall J, Allard S, Bassey SJ, Hersey P, Kerr JP, et al, on behalf of British Committee for Standards in Haematology. Guidelines for the use of platelet transfusions. Br J Haematol. 2017;176:365-94.
U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 2017. [cited 2017 Nov 27]. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf.
Schwartz GJ, Furth SL. Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatr Nephrol. 2007;22:1839-48.
O’Callaghan CA, Shine B, Lasserson DS. Chronic kidney disease: a large-scale population-based study of the effects of introducing the CKD-EPI formula for eGFR reporting. BMJ Open. 2011;1:e000308.
Gorlinger K, Pérez-Ferrer A, Dirkmann D, Saner F, Maegele M, Calatayud AA, et al. The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management. Korean J Anesthesiol. 2019;72:297-322.
Gorlinger K, Pérez-Ferrer A. Algoritmo basado en test POC para el manejo de la hemorragia aguda. In: Pérez-Ferrer A, Garcia-Erce JA, editors. Medicina transfusional. Patient blood management. 2nd ed. Madrid: Editorial Medica Panamericana; 2019. p.75-110.
International Society on Thrombosis and Haemostasis. Sepsis-induced coagulopathy [SIC] algorithm. A practical guide to haemostasis. [cited 2022 Sep 27]. Available from: https://practical-haemostasis.com/Clinical%20Prediction%20Scores/Formulae%20code%20and%20formulae/Formulae/DIC/isth_sic_score.html.
International Society of Blood Transfusion. Criteria for disseminated intravascular coagulation [DIC]. [cited 2023 Mar 11]. Available from: https://www.mdcalc.com/isth-criteria-disseminated-intravascularcoagulation-dic.
Mc Michael AB, Ryerson LM, Ratano D, Fan E, Faraoni D, Annich GM. 2021 ELSO Adult and pediatric anticoagulation guidelines. ASAIO J. 2022;68:303-10.
Almskog LM, Wikman A, Svensson J, Wanecek M, Bottaí M, van der Linden J, et al. Rotational thromboelastometry results are associated with care level in COVID-19. J Thromb Thrombolysis. 2021;51:437-45.
Gonenli MG, Komesti Z, Incir S, Yalçin O, Akay OM. Rotational thromboelastometry reveals distinct coagulation profiles for patients with COVID-19 depending on disease severity. Clin App Thromb Hemost. 2021;27:1-7.
Aires RB, Soares AS, Gomides AP, Nicola AM, Teixeira-Carvalho A, Silva DL, et al. Thromboelastometry demonstrates endogenous coagulation activation in nonsevere and severe COVID-19 patients and has applicability as a decision algorithm for intervention. PLoS One. 2022;14;17:e0262600.
Rodrigues A, Seara Sevivas T, Leal Pereira C, Caiado A, Robalo Nunes A. Viscoelastic tests in the evaluation of haemostatic disorders in SARSCoV-2 infection. Acta Med Port. 2020;33:1-13.
Spieza L, Boscolo A, Poletto F, Cerruti L, Tiberio I, Campeloo E, et al. COVID-19-related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure. Thromb Haemost. 2020;120:998-1000.
Wright FL, Vogler TO, Moore EE, Moore MB, Wohlauer MV, Urbans S, et al. Fibrinolysis shutdown. Correlation with thromboembolic events in severe COVID-19 infection. J Am Coll Surg. 2020;231:193-203e1.
Heinz C, Miesbach W, Hermann E, Sonnatagbauer M, Raimann FJ, Zacharowski K, et al. Greater fibrinolysis resistance but no greater platelet aggregation in critically ill COVID-19 patients. Anesthesiol. 2021;134:457-67.
Creel-Bulos C, Auld SC, Caridi-Scheible M, Barker NA, Friend S, Gaddh M, et al. Fibrinolysis shutdown and thrombosis in a COVID-19 ICU. Shock. 2021;55:316-20.
Zhan H, Chen H, Liu C, Cheng L, Yan S, Li H, et al. Diagnostic value of D-dimer in COVID-19. A meta-analysis and meta-regression. Clin App Thromb Hemost. 2021;27:1-10.
Jaim S, Subhashimi H, Kumari G, Narayan A, Kumar A, Ranjan P, et al. Fibrinogen in COVID-19: interpreting from current evidence. JAM. 2020;9:5-10.
Zou Y, Guo H, Zhang Y, Zhang Z, Liu Y, Wang J, et al. Analysis of coagulation parameters in patients with COVID-19 in Shangai, China. Biosci Trends. 2020;14:285-9.
Henry BM, de Oliveira MH, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020;58:1021-8.
Publicado
Como Citar
Edição
Secção
Licença
Direitos de Autor (c) 2023 Acta Médica Portuguesa
Este trabalho encontra-se publicado com a Creative Commons Atribuição-NãoComercial 4.0.
Todos os artigos publicados na AMP são de acesso aberto e cumprem os requisitos das agências de financiamento ou instituições académicas. Relativamente à utilização por terceiros a AMP rege-se pelos termos da licença Creative Commons ‘Atribuição – Uso Não-Comercial – (CC-BY-NC)’.
É da responsabilidade do autor obter permissão para reproduzir figuras, tabelas, etc., de outras publicações. Após a aceitação de um artigo, os autores serão convidados a preencher uma “Declaração de Responsabilidade Autoral e Partilha de Direitos de Autor “(http://www.actamedicaportuguesa.com/info/AMP-NormasPublicacao.pdf) e a “Declaração de Potenciais Conflitos de Interesse” (http://www.icmje.org/conflicts-of-interest) do ICMJE. Será enviado um e-mail ao autor correspondente, confirmando a receção do manuscrito.
Após a publicação, os autores ficam autorizados a disponibilizar os seus artigos em repositórios das suas instituições de origem, desde que mencionem sempre onde foram publicados e de acordo com a licença Creative Commons
