ABSTRACT

Objective

Hypercoagulopathy related to hyperinflammation may be responsible for mortality and organ failure in coronavirus disease-2019 (COVID-19) patients. Abnormal coagulation profiles were associated with poor outcomes. In this study, we aimed to evaluate the prognostic value of antithrombin (AT) levels in critically ill COVID-19 patients on the intensive care unit (ICU) admission.

Materials and Methods

Four hundred ten critically ill COVID-19 patients were retrospectively analyzed. Inflammatory and conventional coagulation parameters as well as AT activity levels were recorded on the ICU admission. The clinical outcomes of patients were analyzed.

Results

AT levels on the ICU admission were significantly lower in non-survivors than survivors (77.9% vs. 82.5%; p=0.027). Besides AT, D-dimer values of non-survivors were significantly higher than survivors (2775 vs. 1495 µg/L; p<0.001). The cut-off levels for AT and D-dimer were 70.5% and 1585 µg/L, respectively. When AT and D-dimer were analyzed together, mortality estimation was better than only D-dimer or AT.

Conclusion

Low AT levels may be indicative of severe disease and mortality together with high D-dimer levels in COVID-19 patients. Diagnosing and managing AT deficiency in COVID-19 patients could be beneficial for survival. So AT level measurements should be included in the routine panel of laboratory investigation.

Keywords:

Antithrombin, COVID-19, D-dimer, hypercoagulopathy, mortality

References

WHO Coronavirus Disease (COVID-19) Dashboard | WHO Coronavirus Disease (COVID-19) Dashboard (2023) June: 7, 2023: sURL:https://covid19.who.int.

Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 2020;383:120-8.

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 2020;395:1054-62.

Levy JH, Sniecinski RM, Welsby IJ, Levi M. Antithrombin: anti-inflammatory properties and clinical applications. Thromb Haemost 2016;115:712-28.

Mesters RM, Mannucci PM, Coppola R, Keller T, Ostermann H, Kienast J. Factor VIIa and antithrombin III activity during severe sepsis and septic shock in neutropenic patients. Blood 1996;88:881-6.

Gazzaruso C, Paolozzi E, Valenti C, Brocchetta M, Naldani D, Grignani C, et al. Association between antithrombin and mortality in patients with COVID-19. A possible link with obesity. Nutr Metab Cardiovasc Dis 2020;30:1914-9.

White D, MacDonald S, Bull T, Hayman M, de Monteverde-Robb R, Sapsford D, et al. Heparin resistance in COVID-19 patients in the intensive care unit. J Thromb Thrombolysis 2020;50:287-91.

Anaklı İ, Ergin Özcan P, Polat Ö, Orhun G, Alay GH, Tuna V, et al. Prognostic Value of Antithrombin Levels in COVID-19 Patients and Impact of Fresh Frozen Plasma Treatment: A Retrospective Study. Turk J Haematol 2021;38:15-21.

World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance. sURL:https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-whennovel-coronavirus-(ncov)-infection-is-suspected. Accessed January 31, 2020.

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;18:844-7.

Zhang Y, Cao W, Jiang W, Xiao M, Li Y, Tang N, et al. Profile of natural anticoagulant, coagulant factor and anti-phospholipid antibody in critically ill COVID-19 patients. J Thromb Thrombolysis 2020;50:580-6.

Chen-Goodspeed A, Dronavalli G, Zhang X, Podbielski JM, Patel B, Modis K, et al. Antithrombin Activity Is Associated with Persistent Thromboinflammation and Mortality in Patients with Severe COVID-19 Illness. Acta Haematol 2023;146:117-24.

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 2020;18:1023-6.

Yao Y, Cao J, Wang Q, Shi Q, Liu K, Luo Z, et al. D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study. J Intensive Care 2020;8:49.

Dujardin RWG, Hilderink BN, Haksteen WE, Middeldorp S, Vlaar APJ, Thachil J, et al. Biomarkers for the prediction of venous thromboembolism in critically ill COVID-19 patients. Thromb Res 2020;196:308-12.

Sukrisman L, Sinto R. Coagulation profile and correlation between D-dimer, inflammatory markers, and COVID-19 severity in an Indonesian national referral hospital. J Int Med Res 2021;49:3000605211059939.

van Eijk LE, Binkhorst M, Bourgonje AR, Offringa AK, Mulder DJ, Bos EM, et al. COVID‐19: immunopathology, pathophysiological mechanisms, and treatment options. J Pathol 2021;254:307-31.

Takada R, Takazawa T, Takahashi Y, Fujizuka K, Akieda K, Saito S. Risk factors for mechanical ventilation and ECMO in COVID-19 patients admitted to the ICU: A multicenter retrospective observational study. PLoS One 2022;17:e0277641.

Tagami T, Matsui H, Horiguchi H, Fushimi K, Yasunaga H. Antithrombin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: an observational nationwide study. J Thromb Haemost 2014;12:1470-9.

Wada H, Asakura H, Okamoto K, Iba T, Uchiyama T, Kawasugi K, et al. Expert Consensus for the Treatment of Disseminated Intravascular Coagulation in Japan. Thromb Res 2010;125:6-11.

The Prognostic Value of Antithrombin Levels in COVID-19 Patients on Intensive Care Unit Admission

ABSTRACT

References