Prevalence and Impact of Coagulation Dysfunction in COVID-19 in China: A Meta-Analysis
Background The aim of this meta-analysis is to assess the prevalence of coagulation dysfunction in Chinese COVID-19 patients and to determine the association of coagulopathy with the severity and prognosis of COVID-19.
Methods A meta-analysis of the prevalence of different abnormal coagulation indicators in COVID-19 patients in China was performed. The difference of coagulation indicators and the incidence of DIC were compared between severe cases and nonsevere cases as well as nonsurvivors and survivors, respectively.
Results A total of 22 Chinese studies involving 4,889 confirmed COVID-19 inpatients were included. The average D-dimer value of COVID-19 patients is 0.67 µg/mL (95% confidence interval [CI]: 0.56–0.78), and 29.3% (95% CI: 20.1–38.5%) of patients showed elevated D-dimer values. Severe patients had significantly higher D-dimer levels and prolonged prothrombin time (PT) compared with nonsevere patients. Nonsurvivors had significantly higher D-dimer levels, prolonged PT, and decreased platelet count compared with survivors. In total, 6.2% (95% CI: 2.6–9.9%) COVID-19 patients were complicated by disseminated intravascular coagulation (DIC), in which the log risk ratio in nonsurvivors was 3.267 (95% CI: 2.191–4.342, Z = 5.95, p < 0.05) compared with that in survivors.
Conclusion The prevalence of coagulopathy in Chinese COVID-19 inpatients is high, and both the abnormal coagulation indicators and DIC are closely associated with the severity and poor prognosis of these COVID-19 patients. Therefore, attention should be paid to coagulation dysfunction in COVID-19 patients. Closely monitoring of coagulation indicators and application of appropriate anticoagulation may improve the prognosis of COVID-19 inpatients in China.
KeywordsCOVID-19 - coagulopathy - disseminated intravascular coagulation - venous thromboembolism - anticoagulation
All the authors have participated in literature retrieval and viewpoint discussion in this article. S.J. and Y.J. contributed in writing this article. Y.J. did the statistics. X.Y. revised the article. All authors read and approved the final manuscript.
The study does not require ethical approval because the meta-analysis is based on published research and the original data are anonymous.
* These authors contributed equally to this article.
Received: 15 May 2020
Accepted: 26 June 2020
17 July 2020 (online)
© 2020. Thieme. All rights reserved.
Georg Thieme Verlag KG
Stuttgart · New York
- 1 Zhu N, Zhang D, Wang W. et al; China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; 382 (08) 727-733
- 2 Zhou P, Yang XL, Wang XG. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579 (7798): 270-273
- 3 WHO. WHO Director-General's remarks at the media briefing on 2019-nCoV on 11 February 2020. 2020 . Available at: https://www.who.int/dg/speeches/detail/who-director-general-s-remarks-at-the-media-briefing-on-2019-ncov-on-11-february-2020 . Accessed February 11, 2020
- 4 WHO. Coronavirus disease (COVID-19): Situation Report – 104. 2020 . Available at: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200503-covid-19-sitrep-104.pdf?sfvrsn=53328f46_2 . Accessed March 30, 2020
- 5 Weston S, Frieman MB. COVID-19: knowns, unknowns, and questions. MSphere 2020; 5 (02) e00203-20
- 6 Jiang F, Deng L, Zhang L, Cai Y, Cheung CW, Xia Z. Review of the clinical characteristics of Coronavirus Disease 2019 (COVID-19). J Gen Intern Med 2020; 35 (05) 1545-1549
- 7 Petrosillo N, Viceconte G, Ergonul O, Ippolito G, Petersen E. COVID-19, SARS and MERS: are they closely related?. Clin Microbiol Infect 2020; 26 (06) 729-734
- 8 WHO. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. 2020 . Available at: https://www.who.int/csr/sars/country/table2004_04_21/en/ . Accessed January 27, 2020
- 9 Lee N, Hui D, Wu A. et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med 2003; 348 (20) 1986-1994
- 10 Wong RS, Wu A, To KF. et al. Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis. BMJ 2003; 326 (7403): 1358-1362
- 11 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) 1061-1069
- 12 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): 1054-1062
- 13 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 (04) 844-847
- 14 Guan WJ, Ni ZY, Hu Y. et al; China Medical Treatment Expert Group for Covid-19. Clinical characteristics of Coronavirus Disease 2019 in China. N Engl J Med 2020; 382 (18) 1708-1720
- 15 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 (05) 1094-1099
- 16 Zhang G, Zhang J, Wang B, Zhu X, Wang Q, Qiu S. Analysis of clinical characteristics and laboratory findings of 95 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a retrospective analysis. Respir Res 2020; 21 (01) 74
- 17 Liu W, Tao ZW, Wang L. et al. Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Chin Med J (Engl) 2020; 133 (09) 1032-1038
- 18 Shi S, Qin M, Shen B. et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 2020; DOI: 10.1001/jamacardio.2020.0950.
- 19 Yang W, Cao Q, Qin L. et al. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China. J Infect 2020; 80 (04) 388-393
- 20 Chen T, Wu D, Chen H. et al. Clinical characteristics of 113 deceased patients with Coronavirus Disease 2019: retrospective study. BMJ 2020; 368: m1091
- 21 Zhang JJ, Dong X, Cao YY. et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy 2020; DOI: 10.1111/all.14238.
- 22 Deng Y, Liu W, Liu K. et al. Clinical characteristics of fatal and recovered cases of Coronavirus Disease 2019 in Wuhan, China: a retrospective study. Chin Med J (Engl) 2020; 133 (11) 1261-1267
- 23 Yang X, Yu Y, Xu J. et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020; 8 (05) 475-481
- 24 Cao J, Tu WJ, Cheng W. et al. Clinical features and short-term outcomes of 102 patients with corona virus disease 2019 in Wuhan, China. Clin Infect Dis 2020; DOI: 10.1093/cid/ciaa243.
- 25 Wan S, Xiang Y, Fang W. et al. Clinical features and treatment of COVID-19 patients in northeast Chongqing. J Med Virol 2020; 92 (07) 797-806
- 26 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506
- 27 Wang L, He W, Yu X. et al. Coronavirus Disease 2019 in elderly patients: characteristics and prognostic factors based on 4-week follow-up. J Infect 2020; 80 (06) 639-645
- 28 Cai Q, Huang D, Ou P. et al. COVID-19 in a designated infectious diseases hospital outside Hubei Province, China. Allergy 2020; DOI: 10.1111/all.14309.
- 29 Qian GQ, Yang NB, Ding F. et al. Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: a retrospective, multi-centre case series. QJM 2020; DOI: 10.1093/qjmed/hcaa089.
- 30 Chen N, Zhou M, Dong X. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395 (10223): 507-513
- 31 Han H, Yang L, Liu R. et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med 2020; 58 (07) 1116-1120
- 32 Wu C, Chen X, Cai Y. 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; DOI: 10.1001/jamainternmed.2020.0994.
- 33 Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 2014; 14: 135
- 34 Zhang Z, Wu P, Zhang J, Wang S, Zhang G. The effect of statins on microalbuminuria, proteinuria, progression of kidney function, and all-cause mortality in patients with non-end stage chronic kidney disease: a meta-analysis. Pharmacol Res 2016; 105: 74-83
- 35 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557-560
- 36 Wang HJ, Du SH, Yue X, Chen CX. Review and prospect of pathological features of corona virus disease. Fa Yi Xue Za Zhi 2020; 36 (01) 16-20
- 37 Schmitt FCF, Manolov V, Morgenstern J. et al. Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care 2019; 9 (01) 19
- 38 Iba T, Di Nisio M, Thachil J. et al. A proposal of the modification of Japanese Society on Thrombosis and Hemostasis (JSTH) disseminated intravascular coagulation (DIC) diagnostic criteria for sepsis-associated DIC. Clin Appl Thromb Hemost 2018; 24 (03) 439-445
- 39 Zhang Y, Xiao M, Zhang S. et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med 2020; 382 (17) e38
- 40 Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 2020; 18 (06) 1421-1424
- 41 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: 145-147
- 42 Zhai Z, Li C, Chen Y. et al; Prevention Treatment of VTE Associated with COVID-19 Infection Consensus Statement Group. Prevention and treatment of venous thromboembolism associated with Coronavirus Disease 2019 infection: a consensus statement before guidelines. Thromb Haemost 2020; 120 (06) 937-948
- 43 Fogarty H, Townsend L, Ni Cheallaigh C. et al. More on COVID-19 coagulopathy in Caucasian patients. Br J Haematol 2020; 189 (06) 1060-1061
- 44 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 (05) 1023-1026
- 45 Kollias A, Kyriakoulis KG, Dimakakos E, Poulakou G, Stergiou GS, Syrigos K. Thromboembolic risk and anticoagulant therapy in COVID-19 patients: emerging evidence and call for action. Br J Haematol 2020; 189 (05) 846-847