Coronavirus Disease 2019 Coagulopathy: Disseminated Intravascular Coagulation and Thrombotic Microangiopathy—Either, Neither, or Both
Patients with severe coronavirus disease 2019 (COVID-19) infections manifest coagulation abnormalities that have been associated with respiratory deterioration and death.  In addition, many patients with severe COVID-19 infections develop venous thromboembolism, which seems to be related to the coagulopathy. It has also been suggested that undiagnosed pulmonary embolism contributes to a sudden deterioration of pulmonary oxygen exchange that is sometimes seen in patients with COVID-19 infections. 
The coagulopathy associated with COVID-19 mimics other systemic coagulopathies that are regularly seen in severe infections, such as disseminated intravascular coagulation (DIC) or thrombotic microangiopathy (TMA).   However, at the same time, the clinical and laboratory characteristics of the coagulation changes in COVID-19 are distinctly different from the common presentation of these conditions.
08 June 2020 (online)
© 2020. Thieme. All rights reserved.
Thieme Medical Publishers
333 Seventh Avenue, New York, NY 10001, USA.
- 1 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
- 2 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
- 3 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; (e-pub ahead of print) DOI: 10.1016/j.thromres.2020.04.013.
- 4 Yuanliang X, Wang X, Yang P, Zhang S. COVID-19 complicated by acute pulmonary embolism. Radiology: Cardiothoracic Imaging 2020; 2 (02) e200067 (e-pub ahead of print) DOI: 10.1148/ryct.2020200067.
- 5 Danzi GB, Loffi M, Galeazzi G, Gherbesi E. Acute pulmonary embolism and COVID-19 pneumonia: a random association?. Eur Heart J 2020; (e-pub ahead of print) DOI: 10.1093/eurheartj/ehaa254.
- 6 Gando S, Levi M, Toh CH. Disseminated intravascular coagulation. Nat Rev Dis Primers 2016; 2: 16037
- 7 Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999; 341 (08) 586-592
- 8 George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med 2014; 371 (07) 654-666
- 9 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
- 10 Lippi G, Favaloro EJ. D-dimer is associated with severity of coronavirus disease 2019: a pooled analysis. Thromb Haemost 2020; 120 (05) 876-878
- 11 Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta 2020; 506: 145-148
- 12 Brogaard Larsen J, Pasalic L, Hvas AM. Platelets in coronavirus disease. Semin Thromb Hemost 2020; 46 (07) 823-825
- 13 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; 46: 823-825
- 14 Akca S, Haji-Michael P, de Mendonça A, Suter P, Levi M, Vincent JL. Time course of platelet counts in critically ill patients. Crit Care Med 2002; 30 (04) 753-756
- 15 Henry BM, Lippi G, Plebani M. Laboratory abnormalities in children with novel coronavirus disease 2019. Clin Chem Lab Med 2020; (e-pub ahead of print) DOI: 10.1515/cclm-2020-0272.
- 16 Levi M. Platelets in critical illness. Semin Thromb Hemost 2016; 42 (03) 252-257
- 17 Levi M, Sivapalaratnam S. Disseminated intravascular coagulation: an update on pathogenesis and diagnosis. Expert Rev Hematol 2018; 11 (08) 663-672
- 18 Levi M, van der Poll T, Büller HR. Bidirectional relation between inflammation and coagulation. Circulation 2004; 109 (22) 2698-2704
- 19 Taylor Jr FB, Toh CH, Hoots WK, Wada H, Levi M. Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001; 86 (05) 1327-1330
- 20 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; (e-pub ahead of print) DOI: 10.1111/jth.14817.
- 21 Scully M, Goodship T. How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome. Br J Haematol 2014; 164 (06) 759-766
- 22 Fox SE, Atmakbekov A, Harbert JL, Li G, Brown JQ, Vander Heide RS. Pulmonary and cardiac pathologyin Covid-19: the first autopsy series from New Orleans. MedRxiv 2020; (e-pub ahead of print) DOI: 10.1101/2020.04.06.20050575.
- 23 Levi M, Scully M, Singer M. The role of ADAMTS-13 in the coagulopathy of sepsis. J Thromb Haemost 2018; 16 (04) 646-651
- 24 Schwameis M, Schörgenhofer C, Assinger A, Steiner MM, Jilma B. VWF excess and ADAMTS13 deficiency: a unifying pathomechanism linking inflammation to thrombosis in DIC, malaria, and TTP. Thromb Haemost 2015; 113 (04) 708-718
- 25 Gralinski LE, Bankhead III A, Jeng S. et al. Mechanisms of severe acute respiratory syndrome coronavirus-induced acute lung injury. MBio 2013; 4 (04) e00271-e13
- 26 Liu ZH, Wei R, Wu YP. et al. Elevated plasma tissue-type plasminogen activator (t-PA) and soluble thrombomodulin in patients suffering from severe acute respiratory syndrome (SARS) as a possible index for prognosis and treatment strategy. Biomed Environ Sci 2005; 18 (04) 260-264
- 27 Lijnen HR. Matrix metalloproteinases and cellular fibrinolytic activity. Biochemistry (Mosc) 2002; 67 (01) 92-98
- 28 Bellingan GJ. The pulmonary physician in critical care * 6: the pathogenesis of ALI/ARDS. Thorax 2002; 57 (06) 540-546
- 29 Glas GJ, Van Der Sluijs KF, Schultz MJ, Hofstra JJ, Van Der Poll T, Levi M. Bronchoalveolar hemostasis in lung injury and acute respiratory distress syndrome. J Thromb Haemost 2013; 11 (01) 17-25