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Coagulopathy in COVID-19: A Systematic Review
Abstract
Introduction: Corona Virus Disease 2019 (COVID-19) firstly appeared in Wuhan, China in December 2019 and defined as a pandemic in March 2020. COVID-19 divided into asymptomatic, mild, and severe symptoms. Coagulopathy may have happened in severe COVID-19 infection, it was also associated with high mortality in COVID-19 patients. Laboratory examination is the main protocol to identify coagulopathy, thereby it also determined the prognosis of COVID-19 patients with coagulopathy. Here, we review the current evidence describing the mechanism, diagnosis, treatment, and mortality of coagulopathy in COVID-19.
Method: We identify 8 studies and/or review articles evaluating coagulopathy in COVID-19 patients by searching PubMed and EMBASE databases.
Results: DIC is most commonly found in death with COVID-19, the risk of VTE also higher in severe COVID-19 because of immobility and long-term bed rest. Sepsis-induced DIC is associated with organ dysfunction as in the patient with viral infection as in COVID-19 infection. Sepsis-induce Coagulopathy (SIC) score, D-dimer, and prothrombin time (PT) measured at the time the patient classified as severe COVID-19. Higher D-dimer and FDP levels, longer PT and activated partial thromboplastin time (APTT) may have a poor prognosis. Treatment with Low Molecular Weight Heparin (LMWH) effective to reduced 28-day mortality in patients with SIC ≥ 4 and D-dimer > six-fold of the upper limit of normal.
Conclusion: Coagulopathy plays a big role to determine the prognosis of COVID-19 patients. Treatment with LMWH may give some benefits to COVID-19 patients.
Keywords
DOI: http://dx.doi.org/10.19166/med.v8i2.3444
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1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-33.
https://doi.org/10.1056/NEJMoa2001017
2. Beverley Hunt; Andrew Retter; Claire McClintock. Practical guidance for the prevention of thrombosis and management of coagulopathy and disseminated intravascular coagulation of patients infected with COVID-19. 2020.
3. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet [Internet]. 2020;395(10223):507-13.
https://doi.org/10.1016/S0140-6736(20)30211-7
4. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA - J Am Med Assoc. 2020;1-9.
https://doi.org/10.1001/jama.2020.1585
5. Voves C, Wuillemin WA, Zeerleder S. International Society on Thrombosis and Haemostasis score for overt disseminated intravascular coagulation predicts organ dysfunction and fatality in sepsis patients. Blood Coagul Fibrinolysis. 2006;17(6):445-51.
https://doi.org/10.1097/01.mbc.0000240916.63521.2e
6. 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 [Internet]. 2020;395(10229):1054-62. https://doi.org/10.1016/S0140-6736(20)30566-3
7. Rodelo JR, De La Rosa G, Valencia ML, Ospina S, Arango CM, Gómez CI, et al. D-dimer is a significant prognostic factor in patients with suspected infection and sepsis. Am J Emerg Med [Internet]. 2012;30(9):1991-9.
https://doi.org/10.1016/j.ajem.2012.04.033
8. 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.
https://doi.org/10.1111/jth.14768
9. Tom van der Pol; Marcel Levi; Sander J.H. van Deventer. Differential Effects of Anti-Tumor Necrosis Factor Monoclonal Antibodies on Systemic Inflammatory Responses in Experimental Endotoxemia in Chimpanzees. 1994.
https://doi.org/10.1182/blood.V83.2.446.446
10. Madoiwa S. Recent advances in disseminated intravascular coagulation: Endothelial cells and fibrinolysis in sepsis-induced DIC. J Intensive Care. 2015;3(1):1-8.
https://doi.org/10.1186/s40560-015-0075-6
11. Sawdey M, Podor T, Loskutoff D. Regulation of plasminogen activator inhibitor type 1 (PAI-1) gene expression in cultured bovine aortic endothelial cells (BAES). Fibrinolysis. 1988;2:20.
https://doi.org/10.1016/0268-9499(88)90387-6
12. Madoiwa S, Nunomiya S, Ono T, Shintani Y, Ohmori T, Mimuro J, et al. Plasminogen activator inhibitor 1 promotes a poor prognosis in sepsis-induced disseminated intravascular coagulation. Int J Hematol. 2006;84(5):398-405.
https://doi.org/10.1532/IJH97.05190
13. 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 [Internet]. 2020.
https://doi.org/10.1111/jth.14817
14. Gupta N, Zhao YY, Evans CE. The stimulation of thrombosis by hypoxia. Thromb Res [Internet]. 2019;181(January):77-83.
https://doi.org/10.1016/j.thromres.2019.07.013
15. Iba T, Levy JH, Warkentin TE, Thachil J, van der Poll T, Levi M. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost. 2019;17(11):1989-94.
https://doi.org/10.1111/jth.14578
16. Taylor J, Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation: On behalf of the scientific subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and . Thromb Haemost. 2001;86(5):1327-30.
https://doi.org/10.1055/s-0037-1616068
17. Menter DG, Kopetz S, Hawk E, Sood AK, Loree JM, Gresele P, et al. Platelet "first responders" in wound response, cancer, and metastasis. Cancer Metastasis Rev. 2017;36(2):199-213.
https://doi.org/10.1007/s10555-017-9682-0
18. Wada H, Thachil J, Di Nisio M, Mathew P, Kurosawa S, Gando S, et al. Guidance for diagnosis and treatment of disseminated intravascular coagulation from harmonization of the recommendations from three guidelines. J Thromb Haemost. 2013;11(4):761-7.
https://doi.org/10.1111/jth.12155
19. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
https://doi.org/10.1016/S0140-6736(20)30183-5
20. Guan W-J, Ni Z-Y, Hu Y, Liang W-H, Ou C-Q, He J-X, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med [Internet]. 2020;1-13.
https://doi.org/10.1101/2020.02.06.20020974
21. Poterucha TJ, Libby P, Goldhaber SZ. More than an anticoagulant: Do heparins have direct anti-inflammatory effects? Thromb Haemost. 2017;117(3):437-44.
https://doi.org/10.1160/TH16-08-0620
22. Liu X, Li Z, Liu S, Chen Z, Zhao Z, Huang Y, et al. Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction. medRxiv. 2020;2020.02.27.20027557.
https://doi.org/10.1101/2020.02.27.20027557
23. Huang B, Chen Z, Geng L, Wang J, Liang H, Cao Y, et al. Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways. Cell [Internet]. 2019;179(5):1160-1176.e24.
https://doi.org/10.1016/j.cell.2019.10.027
24. Insel PA, Murray F, Yokoyama U, Romano S, Yun H, Brown L, et al. CAMP and Epac in the regulation of tissue fibrosis. Br J Pharmacol. 2012;166(2):447-56.
https://doi.org/10.1111/j.1476-5381.2012.01847.x
25. Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost [Internet]. 2020:0-2.
https://doi.org/10.1111/jth.14810
26. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med [Internet]. 2020 Jul 17 [cited 2021 Jan 27]. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2021436
27. Hariyanto TI, Hardyson W, Kurniawan A. Efficacy and Safety of Tocilizumab for Coronavirus Disease 2019 (Covid-19) Patients: A Systematic Review and Meta-analysis. Drug Res (Stuttg). 2021 Jan 5. Epub ahead of print. PMID: 33401328.
https://doi.org/10.1055/a-1336-2371
28. Widysanto A, Kurniawan A, Lugito NPH, Yuniarti M, Gunawan C, Angela, et al. Experience of using tocilizumab for treatment in Indonesian patients with severe COVID-19. Cytokine. 2021 Feb Vol 138. PMID: 33333393
https://doi.org/10.1016/j.cyto.2020.155393
29. Hariyanto TI, Kurniawan A. Tocilizumab administration is associated with the reduction in biomarkers of coronavirus disease 2019 infection. J Med Virol. 2020;(July):1-5.
30. Hariyanto TI, Japar KV, Kwenandar F, Damay V, Siregar JI, Lugito NPH, et al. Inflammatory and hematologic markers as predictors of severe outcomes in COVID-19 infection: A systematic review and meta-analysis. Am J Emerg Med [Internet]. 2021;41:110-9.
https://doi.org/10.1016/j.ajem.2020.12.076
31. Lugito NP, Kurniawan A, Damay V, Chyntya H, Sugianto N. The role of gut microbiota in SARS-CoV-2 infection: Focus on angiotensin-converting enzyme 2. Curr Med Issues 2020;18:261-3.
https://doi.org/10.4103/cmi.cmi_80_20
32. Hariyanto, T., Japar, K., Damay, V., Kwenandar, F., Sieto, N., & Kurniawan, A. (2020). The Use of ACE inhibitor/ARB in SARS-CoV-2 Patients: A Comprehensive Narrative Review. Asian Journal of Medical Sciences, 11(6), 113-120.
https://doi.org/10.3126/ajms.v11i6.29911
33. Kwenandar F, Japar KV, Damay V, Hariyanto TI, Tanaka M, Lugito NPH, Kurniawan A. Coronavirus disease 2019 and cardiovascular system: a narrative review. Int J Cardiol Heart Vasc. 2020 Jun 3;29:100557. eCollection 2020 Aug. PMID:32550259.
https://doi.org/10.1016/j.ijcha.2020.100557
34. Hariyanto TI, Kurniawan A. Anemia is associated with severe coronavirus disease 2019 (COVID-19) infection. Tranfus Apher Sci. 2020 Dec;59(6):102926. Epub 2020 Aug 28. PMID: 32893135.
https://doi.org/10.1016/j.transci.2020.102926
35. Hariyanto TI, Kurniawan A. Metformin use is associated with reduced mortality rate from coronavirus disease 2019 (COVID-19) infection. Obes Med. 2020 Sep 1;19:100290.
https://doi.org/10.1016/j.obmed.2020.100290
36. Hariyanto TI, Kurniawan A. Statin therapy did not improve the in-hospital outcome of coronavirus disease 2019 (COVID-19) infection. Diabetes Metab Syndr Clin Res Rev. 2020 Nov 1;14(6):1613-5.
https://doi.org/10.1016/j.dsx.2020.08.023
37. Hariyanto TI, Kurniawan A, Statin and outcomes of coronavirus disease 2019 (COVID-19): A systematic review, meta-analysis, and meta-regression, Nutrition, Metabolism and Cardiovascular Diseases. https://doi.org/10.1016/j.numecd.2021
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