Low molecular weight heparin is useful in adult COVID-19 inpatients. Experience during the first Spanish wave
observational study
Palavras-chave:
COVID-19, SARS-CoV-2, Thrombosis, Pulmonary embolismResumo
BACKGROUND: The intensity of the thromboprophylaxis needed as a potential factor for preventing inpatient mortality due to coronavirus disease-19 (COVID-19) remains unclear. OBJECTIVE: To explore the association between anticoagulation intensity and COVID-19 survival. DESIGN AND SETTING: Retrospective observational study in a tertiary-level hospital in Spain. METHODS: Low-molecular-weight heparin (LMWH) status was ascertained based on prescription at admission. To control for immortal time bias, anticoagulant use was analyzed as a time-dependent variable. RESULTS: 690 patients were included (median age, 72 years). LMWH was administered to 615 patients, starting from hospital admission (89.1%). 410 (66.7%) received prophylactic-dose LMWH; 120 (19.5%), therapeutic-dose LMWH; and another 85 (13.8%) who presented respiratory failure, high D-dimer levels (> 3 mg/l) and non-worsening of inflammation markers received prophylaxis of intermediate-dose LMWH. The overall inpatient-mortality rate was 38.5%. The anticoagulant nonuser group presented higher mortality risk than each of the following groups: any LMWH users (HR 2.1; 95% CI: 1.40-3.15); the prophylactic- dose heparin group (HR 2.39; 95% CI, 1.57-3.64); and the users of heparin dose according to biomarkers (HR 6.52; 95% CI, 2.95-14.41). 3.4% of the patients experienced major hemorrhage. 2.8% of the patients developed an episode of thromboembolism. CONCLUSIONS: This observational study showed that LMWH administered at the time of admission was associated with lower mortality among unselected adult COVID-19 inpatients. The magnitude of the benefit may have been greatest for the intermediate-dose subgroup. Randomized controlled trials to assess the benefit of heparin within different therapeutic regimes for COVID-19 patients are required.
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World Health Organization. 2020. WHO Director-General’s Remarks at the Media Briefing on 2019-nCoV on 11 February 2020. Available from: https://www.who.int/dg/speeches/detail/who-director-general-s-remarks-at-the-media-briefing-on-2019-ncov-on-11-february-2020. Accessed in 2021 (May 17).
Lu H, Stratton CW, Tang Y. Outbreak of pneumonia of unknown etiology in Wuhan China: the mystery and the miracle. J Med Virol. 2020;92(4):401-2. PMID: 31950516; https://doi.org/10.1002/jmv.25678.
Chen N, Zhou M, Dong X. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-3. PMID: 32007143; https://doi.org/10.1016/S0140-6736(20)30211-7.
van der Poll T, van de Veerdonk FL, Scicluna BP, et al. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017;1(7):407-20. PMID: 28436424; https://doi.org/10.1038/nri.2017.36
Iba T, Levy JH. Inflammation and thrombosis: roles of neutrophils, platelets and endothelial cells and their interactions in thrombus formation during sepsis. J Thromb Haemost. 2018;16(2):231-41. PMID: 29193703; https://doi.org/10.1111/jth.13911.
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(4):844-7. PMID: 32073213; https://doi.org/10.1111/jth.14768.
Klok FA, Kruip MJHA, van derMeer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191;145-7. PMID: 32291094; https://doi.org/10.1016/j.thromres.2020.04.013.
Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18(5):1094-9. PMID: 32220112; https://doi.org/10.1111/jth.14817.
Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-7. PMID: 20738765; https://doi.org/10.1111/j.1538-7836.2010.04044.x.
Thachil J, Tang N, Gando S. et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020;18(5):1023-6. PMID: 32338827; https://doi.org/10.1111/jth.14810.
Li T, Lu H, Zhang W. Clinical observation and management of COVID-19 patients. Emerg Microbes Infect. 2020;9(1):687-90. PMID: 32208840; https://doi.org/10.1080/22221751.2020.1741327.
Stein BL. Coagulopathy Associated with COVID-19. NEJM Journal Watch [Internet]. 2020. Available from: https://www.jwatch.org/na51254/2020/04/06/coagulopathy-associated-with-covid-19. Accessed in 2021 (May 20).
World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: interim guidance, 28 January 2020. Available from: https://apps.who.int/iris/handle/10665/330893. Accessed in 2021 (May 20).
Taylor FB, Toh CH, Hoots WK, et al. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86(5):1327-30. PMID: 11816725; https://doi.org/10.1055/s-0037-1616068.
Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;8(1):202-4. PMID: 19878532; https://doi.org/10.1111/j.1538-7836.2009.03678.x.
Iba T, Nisio MD, Levy JH, et al. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open. 2017;7(9):e017046. PMID: 28963294; http://dx.doi.org/10.1136/bmjopen-2017-017046.
Lin L, Lu L, Cao W, et al. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020;9(1):727-32. PMID: 32196410; https://doi.org/10.1080/22221751.2020.1746199.
Zhou Y, Fu B, Zheng X, et al. Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. bioRxiv preprint. 2020. https://doi.org/10.1101/2020.02.12.945576.
Inata Y. Should we treat sepsis-induced DIC with anticoagulants? J Intensive Care. 2020;8:18. PMID: 32082582; https://doi.org/10.1186/s40560-020-0435-8.
Fan Y, Jiang M, Gong D, et al. Efficacy and safety of low-molecular-weight heparin in patients with sepsis: a meta-analysis of randomized controlled trials. Sci Rep. 2016;6(3):25984. PMID: 25493972; https://doi.org/10.1097/CCM.0000000000000763.
Umemura Y, Yamakawa K, Ogura H, et al. Efficacy and safety of anticoagulant therapy in three specific populations with sepsis: a meta-analysis of randomized controlled trials. J Thromb Haemost. 2016;14(3):518-30. PMID: 26670422; https://doi.org/10.1111/jth.13230.
Wada H, Thachil J, Di Nisio M et al. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemost. 2013;11(4):761-7. PMID: 23379279; https://doi.org/10.1111/jth.12155.
Kudo D, Hayakawa M, Iijima H, et al. The Treatment Intensity of Anticoagulant Therapy for Patients With Sepsis-Induced Disseminated Intravascular Coagulation and Outcomes: A Multicenter Cohort Study. Clin Appl Thromb Hemost. 2019;25:1-8. PMID: 30919654; https://doi.org/10.1177/1076029619839154.
Morla S. Glycosaminoglycans and Glycosaminoglycan Mimetics in Cancer and Inflammation. Int J Mol Sci. 2019;20(8):1963. PMID: 31013618; https://doi.org/10.3390/ijms20081963.
Hack CE, Aarden LA, Thijs LG. Role of cytokines in sepsis. Adv Immunol. 1997;66:101-95. PMID: 9328641; https://doi.org/10.1016/s0065-2776(08)60597-0.
Varki A, Cummings RD, Esko JD, et al. Essentials of Glycobiology. 2nd ed. New York, NY, USA: Cold Spring Harbor Laboratory Press; 2009.
Ghezzi S, Cooper L, Rubio A, et al. Heparin prevents Zika virus induced-cytopathic effects in human neural progenitor cells. Antiviral Res. 2017;140:13-7. PMID: 28063994; https://doi.org/10.1016/j.antiviral.2016.12.023.
Di Minno A, Ambrosino P, Calcaterra I, et al. COVID-19 and Venous Thromboembolism: A Meta-analysis of Literature Studies. Semin Thromb Hemost. 2020;46(7):763-71. PMID: 32882719; https://doi.org/10.1055/s-0040-1715456.
Jiménez D, García-Sanchez A, Rali P, et al. Incidence of VTE and Bleeding Among Hospitalized Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis. CHEST 2021; 159(3):1182-96. PMID: 33217420; https://doi.org/10.1016/j.chest.2020.11.005.
Tritschler T, Mathieu ME, Skeith L, et al. Anticoagulant interventions in hospitalized patients with COVID-19: A scoping review of randomized controlled trials and call for international collaboration. J Thromb Haemost. 2020; 18(11):2958-67. PMID: 32888372; https://doi.org/10.1111/jth.15094.
Rentsch CT, Beckman JA, Tomlinson L. Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study. BMJ. 2021;372:n311. PMID: 33574135; https://doi.org/10.1136/bmj.n311.
ATTACC. ACTIV-4a & REMAP-CAP multiplatform RCT. Results of interim. Available from: analysis. https://www.attacc.org/presentations. Accessed in 2021 (May 20).
Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9. PMID: 32031570; https://doi.org/10.1001/jama.2020.1585.
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. PMID: 32171076; https://doi.org/10.1016/S0140-6736(20)30566-3.
Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-20. PMID: 32109013; https://doi.org/10.1056/NEJMoa2002032.
Lippi G, Favaloro EJ. D-dimer is Associated with Severity of Coronavirus Disease 2019: A Pooled Analysis. Thromb Haemost. 2020;120(5):876-8. PMID: 32246450; https://doi.org/10.1055/s-0040-1709650.
Petrilli CM, Jones SA, Yang J. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York city: prospective cohort study. BMJ. 2020:369:m1966. PMID: 32444366; https://doi.org/10.1136/bmj.m1966.
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