Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

Ning Tang, Huan Bai, Xing Chen, Jiale Gong, Dengju Li, Ziyong Sun, Ning Tang, Huan Bai, Xing Chen, Jiale Gong, Dengju Li, Ziyong Sun

Abstract

Background: A relatively high mortality of severe coronavirus disease 2019 (COVID-19) is worrying, and the application of heparin in COVID-19 has been recommended by some expert consensus because of the risk of disseminated intravascular coagulation and venous thromboembolism. However, its efficacy remains to be validated.

Methods: Coagulation results, medications, and outcomes of consecutive patients being classified as having severe COVID-19 in Tongji hospital were retrospectively analyzed. The 28-day mortality between heparin users and nonusers were compared, as was a different risk of coagulopathy, which was stratified by the sepsis-induced coagulopathy (SIC) score or D-dimer result.

Results: There were 449 patients with severe COVID-19 enrolled into the study, 99 of them received heparin (mainly with low molecular weight heparin) for 7 days or longer. D-dimer, prothrombin time, and age were positively, and platelet count was negatively, correlated with 28-day mortality in multivariate analysis. No difference in 28-day mortality was found between heparin users and nonusers (30.3% vs 29.7%, P = .910). But the 28-day mortality of heparin users was lower than nonusers in patients with SIC score ≥4 (40.0% vs 64.2%, P = .029), or D-dimer >6-fold of upper limit of normal (32.8% vs 52.4%, P = .017).

Conclusions: Anticoagulant therapy mainly with low molecular weight heparin appears to be associated with better prognosis in severe COVID-19 patients meeting SIC criteria or with markedly elevated D-dimer.

Keywords: D-dimer; coagulopathy; coronavirus disease 2019; low molecular weight heparin; sepsis.

© 2020 International Society on Thrombosis and Haemostasis.

Figures

Figure 1
Figure 1
The enrollment of patients with severe COVID‐19
Figure 2
Figure 2
A paired bar chart showing the mortality between heparin users and nonusers in stratified patients. D‐D, D‐dimer; SIC+, SIC score ≥ 4; SIC−, SIC score P < .05 between heparin users and nonusers

References

    1. 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.
    1. 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.
    1. 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 doi: 10.1111/jth.14768.
    1. Singer M., Deutschman C.S., Seymour C.W., et al. The third international consensus definitions for sepsis and septic shock (Sepsis‐3) JAMA. 2016;315(8):801–810.
    1. Shanghai Clinical Treatment Expert Group for. COVID‐19 Comprehensive treatment and management of coronavirus disease 2019: expert consensus statement from Shanghai (in Chinese) Chin J Infect Dis. 2020;38 doi: 10.3760/cma.j.issn.1000-6680.2020.0016.
    1. Iba T., Levy J.H., Warkentin T.E., et al. Diagnosis and management of sepsis‐induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost. 2019;17(11):1989–1994.
    1. Iba T., Nisio M.D., Levy J.H., Kitamura N., Thachil J. New criteria for sepsis‐induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open. 2017;7(9)
    1. World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance. Published January 28, 2020. . Accessed January 31, 2020
    1. National Health Commission of China. The diagnosis and treatment plan for the novel coronavirus disease (the seventh edition). 2020.
    1. Vincent J.L., Moreno R., Takala J., et al. The SOFA (Sepsis‐related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis‐Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707–710.
    1. Venclauskas L., Llau J.V., Jenny J.Y., Kjaersgaard‐Andersen P., Jans Ø., ESA VTE Guidelines Task Force European guidelines on perioperative venous thromboembolism prophylaxis: day surgery and fast‐track surgery. Eur J Anaesthesiol. 2018;35(2):134–138.
    1. Levi M., van der Poll T. Coagulation and sepsis. Thromb Res. 2017;149:38–44.
    1. Schmitt F.C.F., 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(1):19.
    1. Gupta N., Zhao Y.Y., Evans C.E. The stimulation of thrombosis by hypoxia. Thromb Res. 2019;181:77–83.
    1. Luo W, Yu H, Gou J, et al.Clinical pathology of critical patient with novel coronavirus pneumonia (COVID‐19). Preprints. 2020, 2020020407.
    1. Poterucha T.J., Libby P., Goldhaber S.Z. More than an anticoagulant: do heparins have direct anti‐inflammatory effects? Thromb Haemost. 2017;117(3):437–444.
    1. Stein P.D., Kayali F., Olson R.E., Milford C.E. Pulmonary thromboembolism in Asians/Pacific Islanders in the United States: analysis of data from the National Hospital Discharge Survey and the United States Bureau of the Census. Am J Med. 2004;116(7):435–442.
    1. Zakai N.A., McClure L.A. Racial differences in venous thromboembolism. J Thromb Haemost. 2011;9(10):1877–1882.
    1. Aikawa N., Shimazaki S., Yamamoto Y., et al. Thrombomodulin alfa in the treatment of infectious patients complicated by disseminated intravascular coagulation: subanalysis from the phase 3 trial. Shock. 2011;35(4):349–354.
    1. Liu X.L., Wang X.Z., Liu X.X., et al. Low‐dose heparin as treatment for early disseminated intravascular coagulation during sepsis: a prospective clinical study. Exp Ther Med. 2014;7(3):604–608.
    1. Nishida O., Ogura H., Egi M., et al. The Japanese clinical practice guidelines for management of sepsis and septic shock 2016 (J‐SSCG 2016) Acute Med Surg. 2018;5(1):3–89.
    1. Umemura Y., Yamakawa K., Ogura H., Yuhara H., Fujimi S. 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):518–530.
    1. Iba T., Gando S., Thachil J. Anticoagulant therapy for sepsis‐associated disseminated intravascular coagulation: the view from Japan. J Thromb Haemost. 2014;12(7):1010–1019.
    1. Menter D.G., Kopetz S., Hawk E., et al. Platelet "first responders" in wound response, cancer, and metastasis. Cancer Metastasis Rev. 2017;36(2):199–213.
    1. Sun H., Wang X., Degen J.L., Ginsburg D. Reduced thrombin generation increases host susceptibility to group A streptococcal infection. Blood. 2009;113(6):1358–1364.
    1. Dong L., Hu S., Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID‐19) Drug Discov Ther. 2020;14(1):58–60.

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