Systemic Inflammatory Response Syndrome Is a Major Contributor to COVID-19–Associated Coagulopathy
Authors: Paul Masi, Guillaume Hékimian, Manon Lejeune, Juliette Chommeloux, Cyrielle Desnos, Marc Pineton De Chambrun, Isabelle Martin-Toutain, Ania Nieszkowska, Guillaume Lebreton, Nicolas Bréchot, Matthieu Schmidt, Charles Edouard Luyt, Alain Combes, Corinne Frere
Journal: Circulation (2020)

Coronavirus disease 2019 (COVID-19) is associated with a systemic coagulopathy 1 favoring thromboembolic complications, which occur in 15% to 30% of critically ill patients with COVID-19. 2,3This coagulopathy remains poorly documented and data on thrombin generation and fibrinolysis are lacking.We characterized the coagulation and fibrinolysis profiles of patients with CO-VID-19 with acute respiratory distress syndrome (ARDS).From October 2019 to April 2020, 28 consecutive patients with severe ARDS were referred to our tertiary intensive care unit and included in this prospective single-center cohort study.The protocol was approved by a research ethics committee (CPP Ouest III, 2019-A01160-57), and the study was conducted in accordance with the Declaration of Helsinki.Informed consent was obtained from patients or their relatives.Blood samples were collected on admission for a comprehensive coagulation/fibrinolytic pathways analysis.To better assess the in vivo dynamics of clot formation, stabilization, and lysis, we used a global coagulation assay assessing changes in viscoelastic properties of whole blood.We compared 11 patients with ARDS included before the COVID-19 pandemic (influenza pneumonia, n=4; bacterial pneumonia, n=2; other causes of ARDS, n=5) with 17 patients with COVID-19.Baseline characteristics of the patients with and without COVID-19 did not differ and are presented in the Table .Briefly, the median age was 45 years; most patients were men (68%), overweight (32.1%), or obese (57.1%); and a few of them had additional comorbidities.On admission, all patients were receiving thromboprophylaxis according to current guidelines.Pulmonary embolism was incidentally diagnosed in 3 out of 17 patients with CO-VID-19.Coagulation and fibrinolysis profiles are presented in the Table.In addition, von Willebrand factor antigen and activity did not differ between groups and were 3-to 4-fold higher than the upper limit of normal range (median, 4.44 and 2.86 IU/mL, respectively, in the overall population).Compared with patients without COVID-19, patients with COVID-19 exhibited significantly higher levels of procoagulant factors, mainly fibrinogen (median, 810 mg/dL versus 710; P=0.03), factor V (median, 1.53 IU/mL versus 0.73; P<0.0001), factor VIII (median, 2.97 IU/mL versus 1.61; P=0.03), and acute phase reactants including C-reactive protein (P=0.05) and α1-acid glycoprotein (P=0.02).All of these measures were strongly correlated with each other (P<0.05 for all correlations).In contrast, antithrombin, protein C, and protein S levels were within the normal range and did not differ between groups.Prothrombin fragment 1 and 2 levels did not differ between patients with and without COVID-19 and were 2-to 3-fold higher than the upper limit of normal range.Thrombin-antithrombin complex levels were increased in both groups but significantly lower in patients with COVID-19 (median, 7.69 µg/L versus 22.63; P=0.03).Fibrinolysis profiles showed factor XIII, plasminogen, and