High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study

Julie Helms, Charles Tacquard, François Severac, Ian Leonard-Lorant, Mickaël Ohana, Xavier Delabranche, Hamid Merdji, Raphaël Clere-Jehl, Malika Schenck, Florence Fagot Gandet, Samira Fafi-Kremer, Vincent Castelain, Francis Schneider, Lélia Grunebaum, Eduardo Anglés-Cano, Laurent Sattler, Paul-Michel Mertes, Ferhat Meziani, CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis), Julie Helms, Charles Tacquard, François Severac, Ian Leonard-Lorant, Mickaël Ohana, Xavier Delabranche, Hamid Merdji, Raphaël Clere-Jehl, Malika Schenck, Florence Fagot Gandet, Samira Fafi-Kremer, Vincent Castelain, Francis Schneider, Lélia Grunebaum, Eduardo Anglés-Cano, Laurent Sattler, Paul-Michel Mertes, Ferhat Meziani, CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis)

Abstract

Purpose: Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.

Methods: All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.

Results: 150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points). Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting. Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO. Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant. Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs. 2.1%, p < 0.008). Coagulation parameters significantly differed between the two groups.

Conclusion: Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications. Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.

Keywords: ARDS; COVID-19; Coagulopathy; Lupus anticoagulant; Thrombosis.

Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
66-year-old man at day 8 of ICU stay for ARDS secondary to Covid-19. CTPA demonstrating a proximal right pulmonary artery luminal defect and major bilateral alveolar consolidation
Fig. 2
Fig. 2
Coagulation parameters of the matched COVID-19 ARDS (n = 77 patients); and non-COVID-19 ARDS patients (n = 145 patients); aPTT: activated partial thromboplastin time, PT: prothrombin time

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