Potential benefits of anticoagulant doses of low molecular weight heparin in COVID-19: An observational retrospective study

Submitted: 31 March 2021
Accepted: 6 August 2021
Published: 21 September 2021
Abstract Views: 1085
PDF: 322
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Hypercoagulability is a common complication of the systemic inflammation related to coronavirus disease 2019 creating debate within the critical care community on the therapeutic utility of Low Molecular Weight Heparin (LMWH). We collected data on consecutive patients with COVID-19 admitted to the Emergency Department of Castel San Giovanni Hospital, between February 29th and April 7th, 2020. Exclusion criteria were age <18 years, hospital stay <7 days, patients on dialysis and patients who had been transferred to other centers for which we could not collect data. Of the 257 patients included in the study, 49 (19.1%) died during hospitalization. We considered a wide set of variables as independent variables (age, sex, comorbidities and in-hospital treatments). We used a multivariate logistic regression model and, being heparin the only one therapy affecting survival rate, we compared prophylactic LMWH (p-LMWH) and Therapeutic LMWH (T-LMWH) groups. Kaplan Meier curve showed a higher survival probability in the T-LMWH and the difference between the two groups was statistically significant according to the log-rank or Mantel- Haenszel test (p< 0.0001). In a stratified analysis by ventilation type, the subgroup of patients who benefited from therapeutic LMWH was that in non-invasive mechanical ventilation. Using a multivariate analysis and adjusting for the drugs intake, TLMWH was the only therapy impacting on survival (HR 0.293, p <0.001). No fatal bleeding was observed. Therapeutic dose of LMWH in patients admitted to hospital with COVID-19 pneumonia was 70 associated with a decrease risk of intra-hospital mortality.

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Citations

Kalil AC. Treating COVID-19-off-label drug use, compassionate use, and randomized clinical trials during pandemics. JAMA 2020;323:1897-8. DOI: https://doi.org/10.1001/jama.2020.4742
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 280 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507-13. DOI: https://doi.org/10.1016/S0140-6736(20)30211-7
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506. DOI: https://doi.org/10.1016/S0140-6736(20)30183-5
Tang N, Li D, Wang X, et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020;18:844-7. DOI: https://doi.org/10.1111/jth.14768
Avila J, Long B, Holladay B, Gottilieb M. Thrombotic complications of COVID-19, Am J Emerg Medicine 2021;39:213-8. DOI: https://doi.org/10.1016/j.ajem.2020.09.065
Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020;191:145-7. DOI: https://doi.org/10.1016/j.thromres.2020.04.013
Reed A, Howard C, Barakat M, Navi A. Simultaneous arterial and venous thromboembolic events associated with COVID- 19. A case report. Emerg Care J 2021;17:9718. DOI: https://doi.org/10.4081/ecj.2021.9718
Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients with severe SARS288 CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 2020;46:1089-8.
Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID‐19. J Thromb Haemost 2020;18:1023-6. DOI: https://doi.org/10.1111/jth.14810
World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (‎2019-nCoV)‎ infection is suspected: interim guidance, 28 January 2020. World Health Organization, 2020. Available from: https://apps.who.int/iris/handle/10665/330893
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;18:1094-9. DOI: https://doi.org/10.1111/jth.14817
Hirsh J, Warkentin TE, Shaughnessy SG, et al. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest 2001;119:64S-94S. DOI: https://doi.org/10.1378/chest.119.1_suppl.64S
Mousavi S, Moradi M, Khorshidahmad T, Motamedi M. Anti-Inflammatory Effects of Heparin and Its Derivatives: A Systematic Review. Adv Pharmacol Sci 2015;2015:507151. DOI: https://doi.org/10.1155/2015/507151
Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect 2020;9:727-32. DOI: https://doi.org/10.1080/22221751.2020.1746199
Johnson Z, Kosco-Vilbois MH, Herren S, et al. Interference with heparin binding and oligomerization creates a novel anti-inflammatory strategy targeting the chemokine system. J Immunol 2004;173:5776-85. DOI: https://doi.org/10.4049/jimmunol.173.9.5776
Thachil J. The versatile heparin in COVID-307 19. J Thromb Haemost 2020;18:1020-2. DOI: https://doi.org/10.1111/jth.14821
Venclauskas L, Llau JV, Jenny JY, Kjaersgaard-Andersen P. ESA VTE Guidelines on perioperative venous thromboembolism prophylaxis: day surgery and fast track surgery. Eur J Anaesthesiol 2018;35:134-8. DOI: https://doi.org/10.1097/EJA.0000000000000706
Schünemann HJ, Cushman M, Burnett AE, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv 2018;2:3198-225. DOI: https://doi.org/10.1182/bloodadvances.2018022954
Kaatz S, Ahmad D, Spyropoulos AC, Schulman S; Subcommittee on Control of Anticoagulation. 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. 2015;13:2119-26. DOI: https://doi.org/10.1111/jth.13140
Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis 2020;94:91-5. DOI: https://doi.org/10.1016/j.ijid.2020.03.017
Livingston E, Bucher K. Coronavirus Disease 2019 (COVID-19) in Italy. JAMA 2020;323:1335. DOI: https://doi.org/10.1001/jama.2020.4344
Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 2003;23:168-75. DOI: https://doi.org/10.1161/01.ATV.0000051384.43104.FC
Wichmann D, Sperhake J, et al. Autopsy findings and venous thromboembolism in patients with COVID-19: A prospective cohort study. Ann Intern Med 2020;173:268-77. DOI: https://doi.org/10.7326/L20-1206
Helms, C. Tacquard, F. Severac, I. et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 2020;46:1089-98. DOI: https://doi.org/10.1007/s00134-020-06062-x
Schutgens RE. DOAC in COVID-19: Yes or No? Hemasphere 2020;5:e526. DOI: https://doi.org/10.1097/HS9.0000000000000526
Talasaz AH, Sadeghipour P, Kakavand H. Recent randomized trials of antithrombotic therapy for patients with COVID-19: JACC state-of-the-art review. J Am Coll Cardiol 2021;77:1903-21. DOI: https://doi.org/10.1016/j.jacc.2021.02.035

How to Cite

Aschieri, D., Stabile, M., Maestri, C., Rosato, L., Coccia, M. G., Novara, P., Lanati, G., Di Dio, M. T., Franco, C., Bisceglie, G., Leddi, G., Fabrizi, E., Rucci, P., & Taliani, G. (2021). Potential benefits of anticoagulant doses of low molecular weight heparin in COVID-19: An observational retrospective study. Emergency Care Journal, 17(3). https://doi.org/10.4081/ecj.2021.9795