Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomized clinical trial.

Anticoagulant COVID-19 Haemorrhage Thromboembolism

Journal

Journal of thrombosis and thrombolysis
ISSN: 1573-742X
Titre abrégé: J Thromb Thrombolysis
Pays: Netherlands
ID NLM: 9502018

Informations de publication

Date de publication:
18 May 2024
Historique:
accepted: 26 04 2024
medline: 19 5 2024
pubmed: 19 5 2024
entrez: 18 5 2024
Statut: aheadofprint

Résumé

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.

Identifiants

pubmed: 38762708
doi: 10.1007/s11239-024-02995-y
pii: 10.1007/s11239-024-02995-y
doi:

Banques de données

ClinicalTrials.gov
['NCT04394377']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Références

Ackermann M, Verleden SE, Kuehnel M et al (2020) Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med 383:120–128
doi: 10.1056/NEJMoa2015432 pubmed: 32437596 pmcid: 7412750
Zhou F, Yu T, Du R et al (2020) Clinical course and risk factors for mortality of adult in patients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395:1054–1062
doi: 10.1016/S0140-6736(20)30566-3 pubmed: 32171076 pmcid: 7270627
Gungor B, Atici A, Baycan OF et al (2021) Elevated D-dimer levels on admission are associated with severity and increased risk of mortality in COVID-19: a systematic review and meta-analysis. Am J Emerg Med 39:173–179
doi: 10.1016/j.ajem.2020.09.018 pubmed: 33069541
Jiménez D, García-Sanchez A, Rali P et al (2021) Incidence of VTE and bleeding among hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis. Chest 159:1182–1196
doi: 10.1016/j.chest.2020.11.005 pubmed: 33217420
Shi S, Qin M, Shen B et al (2020) Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 5:802–810
doi: 10.1001/jamacardio.2020.0950 pubmed: 32211816 pmcid: 7097841
Lopes RD, de Barros E, Silva PGM, Furtado RHM et al (2021) Randomized clinical trial to evaluate a routine full anticoagulation Strategy in Patients with Coronavirus Infection (SARS-CoV2) admitted to hospital: Rationale and design of the ACTION (AntiCoagulaTlon cOroNavirus)-Coalition IV trial. Am Heart J 238:1–11
doi: 10.1016/j.ahj.2021.04.005 pubmed: 33891907 pmcid: 8057688
Lopes RD, de Barros e Silva PGM, Furtado RHM et al (2021) Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet 397:2253–2263
doi: 10.1016/S0140-6736(21)01203-4 pubmed: 34097856 pmcid: 8177770
The REMAP-CAP, ACTIV-4a, and ATTACC Investigators (2021) Therapeutic anticoagulation with heparin in critically ill patients with COVID-19. N Engl J Med published online Aug 4. https://doi.org/10.1056/NEJMoa2103417
The ATTACC, ACTIV-4a, and REMAP-CAP Investigators (2021) Therapeutic anticoagulation with heparin in noncritically ill patients with COVID-19. N Engl J Med published online Aug 4. https://doi.org/10.1056/NEJMoa2105911
Bikdeli B, Talasaz AH, Rashidi F et al (2022) Intermediate-dose versus standard-dose prophylactic anticoagulation in patients with COVID-19 admitted to the intensive care unit: 90-day results from the INSPIRATION randomized trial. Thromb Haemost 122(1):131–141
doi: 10.1055/a-1485-2372 pubmed: 33865239
Spyropoulos AC, Goldin M, Giannis D et al (2021) Efficacy and safety of therapeutic-dose heparin vs standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients With COVID-19: the HEP-COVID randomized clinical trial. JAMA Intern Med 181(12):1612–1620
doi: 10.1001/jamainternmed.2021.6203 pubmed: 34617959 pmcid: 8498934
Sholzberg M, Tang GH, Rahhal H et al (2021) Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial. BMJ 375:n2400
doi: 10.1136/bmj.n2400 pubmed: 34649864
Bohula EA, Berg DD, Lopes MS et al (2022) Anticoagulation and antiplatelet therapy for prevention of venous and arterial thrombotic events in critically Ill patients with COVID-19: COVID-PACT. Circulation 146(18):1344–1356
doi: 10.1161/CIRCULATIONAHA.122.061533 pubmed: 36036760 pmcid: 9624238
Stone GW, Farkouh ME, Lala A et al (2023) Randomized trial of anticoagulation strategies for noncritically ill patients hospitalized with COVID-19. J Am Coll Cardiol 81(18):1747–1762. https://doi.org/10.1016/j.jacc.2023.02.041
Kaatz S, Ahmad D, Spyropoulos AC et al (2015) Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 13:2119–2126
doi: 10.1111/jth.13140 pubmed: 26764429
Wattanakit K, Cushman M, Stehman-Breen C et al (2008) Chronic kidney disease increases risk for venous thromboembolism. J Am Soc Nephrol 19(1):135–140
doi: 10.1681/ASN.2007030308 pubmed: 18032796 pmcid: 2391038
Helms J, Tacquard C, Severac F et al (2020) High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 46(6):1089–1098
doi: 10.1007/s00134-020-06062-x pubmed: 32367170 pmcid: 7197634

Auteurs

Pedro Gabriel Melo de Barros E Silva (PGM)

Brazilian Clinical Research Institute, São Paulo, Brazil.
Hcor Research Institute, São Paulo, Brazil.
Hospital Samaritano Paulista, São Paulo, Brazil.
Centro Universitario São Camilo, São Paulo, Brazil.

Remo H M Furtado (RHM)

Brazilian Clinical Research Institute, São Paulo, Brazil.
Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil.
Instituto Do Coração (InCor), Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Mariana Silveira de Alcântara Chaud (MS)

Hospital Samaritano Paulista, São Paulo, Brazil.

Ariane Vieira Scarlatelli Macedo (AVS)

Brazilian Clinical Research Institute, São Paulo, Brazil.

Bruna Bronhara (B)

Brazilian Clinical Research Institute, São Paulo, Brazil.

Lucas Petri Damiani (LP)

Brazilian Clinical Research Institute, São Paulo, Brazil.

Lilian Mazza Barbosa (LM)

Brazilian Clinical Research Institute, São Paulo, Brazil.

Mayra Akimi Suiama (MA)

Brazilian Clinical Research Institute, São Paulo, Brazil.

Eduardo Ramacciotti (E)

Brazilian Clinical Research Institute, São Paulo, Brazil.

Priscilla de Aquino Martins (P)

Hospital Estadual Dr Jayme Santos Neves, Serra, Brazil.

Aryadne Lyrio de Oliveira (AL)

Hospital Estadual Dr Jayme Santos Neves, Serra, Brazil.

Vinicius Santana Nunes (VS)

Hospital Estadual Dr Jayme Santos Neves, Serra, Brazil.

Luiz Eduardo Fonteles Ritt (LEF)

Instituto D'Or de Pesquisa E Ensino, Hospital Cárdio Pulmonar, Salvador, Brazil.
Escola Bahiana de Medicina, Salvador, Brazil.

Ana Thereza Rocha (AT)

Instituto D'Or de Pesquisa E Ensino, Hospital Cárdio Pulmonar, Salvador, Brazil.
Escola Bahiana de Medicina, Salvador, Brazil.
Universidade Federal da Bahia, Salvador, Brazil.

Lucas Tramujas (L)

Hcor Research Institute, São Paulo, Brazil.

Sueli V Santos (SV)

Hcor Research Institute, São Paulo, Brazil.

Dario Rafael Abregu Diaz (DRA)

Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil.

Lorena Souza Viana (LS)

Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil.

Lívia Maria Garcia Melro (LMG)

Hospital Samaritano Paulista, São Paulo, Brazil.

Estêvão Lanna Figueiredo (EL)

Hospital Vera Cruz, Belo Horizonte, Brazil.
NUPEC, Belo Horizonte, Brazil.

Fernando Carvalho Neuenschwander (FC)

Hospital Vera Cruz, Belo Horizonte, Brazil.
NUPEC, Belo Horizonte, Brazil.

Marianna Deway Andrade Dracoulakis (MDA)

Hospital Naval Marcílio Dias, Rio de Janeiro, Brazil.

Rodolfo Godinho Souza Dourado Lima (RGSD)

Hospital Naval Marcílio Dias, Rio de Janeiro, Brazil.

Vicente Cés de Souza Dantas (VC)

Hospital Santa Paula, São Paulo, Brazil.

Anne Cristine Silva Fernandes (ACS)

Hospital Santa Paula, São Paulo, Brazil.

Otávio Celso Eluf Gebara (OCE)

Santa Casa de Misericórdia de Votuporanga, Votuporanga, Brazil.

Mauro Esteves Hernandes (ME)

Hospital das Clínicas da Faculdade de Medicina de Botucatu, Botucatu, Brazil.

Diego Aparecido Rios Queiroz (DAR)

Brazilian Research in Intensive Care Network-BRICNet, São Paulo, Brazil.

Viviane C Veiga (VC)

BP-A Beneficência Portuguesa de São Paulo, São Paulo, Brazil.
Hospital Universitário da Universidade Estadual de Londrina, Londrina, Brazil.

Manoel Fernandes Canesin (MF)

Hospital Felício Rocho, Belo Horizonte, Brazil.

Leonardo Meira de Faria (LM)

Santa Casa de Misericórdia da Bahia-Hospital Santa Izabel, Salvador, Brazil.

Gilson Soares Feitosa-Filho (GS)

Hospital Moinhos de Vento, Porto Alegre, Brazil.

Marcelo Basso Gazzana (MB)

Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil.

Idelzuíta Leandro Liporace (IL)

Hospital de Amor de Barretos (Pio XII), Barretos, Brazil.

Aline de Oliveira Twardowsky (A)

Hospital de Base de São José Do Rio Preto, São José Do Rio Preto, Brazil.

Lilia Nigro Maia (LN)

Pain and Intensive Care Department, Federal University of Sao Paulo (UNIFESP), São Paulo, Brazil.

Flávia Ribeiro Machado (FR)

BP-A Beneficência Portuguesa de São Paulo, São Paulo, Brazil.
Instituto Socrates Guanaes, São Paulo, Brazil.

Alexandre de Matos Soeiro (A)

Instituto Do Coração (InCor), Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Germano Emílio Conceição-Souza (GE)

International Research Center, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.

Luciana Armaganijan (L)

Brazilian Clinical Research Institute, São Paulo, Brazil.

Patrícia O Guimarães (PO)

Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil.

Regis G Rosa (RG)

BP-A Beneficência Portuguesa de São Paulo, São Paulo, Brazil.
Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil.

Luciano C P Azevedo (LCP)

Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil.
BP-A Beneficência Portuguesa de São Paulo, São Paulo, Brazil.

John H Alexander (JH)

Duke Clinical Research Institute, Duke University Medical Center, 2400 Pratt Street, Box 3850, Durham, NC, 27705, USA.

Alvaro Avezum (A)

Imperial College London, London, UK.

Otávio Berwanger (O)

Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil.
Imperial College London, London, UK.
The George Institute for Global Health UK, London, UK.

Alexandre B Cavalcanti (AB)

Hcor Research Institute, São Paulo, Brazil.
BP-A Beneficência Portuguesa de São Paulo, São Paulo, Brazil.

Renato D Lopes (RD)

Brazilian Clinical Research Institute, São Paulo, Brazil. renato.lopes@dm.duke.edu.
Duke Clinical Research Institute, Duke University Medical Center, 2400 Pratt Street, Box 3850, Durham, NC, 27705, USA. renato.lopes@dm.duke.edu.

Classifications MeSH