Elevated D-dimers and lack of anticoagulation predict PE in severe COVID-19 patients

Abstract

Background: Coronavirus disease 2019 (COVID-19) may predispose to venous thromboembolism. We determined factors independently associated with computed tomography pulmonary angiography (CTPA)-confirmed pulmonary embolism (PE) in hospitalised severe COVID-19 patients.

Methods: Among all (n=349) patients hospitalised for COVID-19 in a university hospital in a French region with a high rate of COVID-19, we analysed patients who underwent CTPA for clinical signs of severe disease (oxygen saturation measured by pulse oximetry ≤93% or breathing rate ≥30 breaths·min^-1) or rapid clinical worsening. Multivariable analysis was performed using Firth penalised maximum likelihood estimates.

Results: 162 (46.4%) patients underwent CTPA (mean±sd age 65.6±13.0 years; 67.3% male (95% CI 59.5-75.5%). PE was diagnosed in 44 (27.2%) patients. Most PEs were segmental and the rate of PE-related right ventricular dysfunction was 15.9%. By multivariable analysis, the only two significant predictors of CTPA-confirmed PE were D-dimer level and the lack of any anticoagulant therapy (OR 4.0 (95% CI 2.4-6.7) per additional quartile and OR 4.5 (95% CI 1.1-7.4), respectively). Receiver operating characteristic curve analysis identified a D-dimer cut-off value of 2590 ng·mL^-1 to best predict occurrence of PE (area under the curve 0.88, p<0.001, sensitivity 83.3%, specificity 83.8%). D-dimer level >2590 ng·mL^-1 was associated with a 17-fold increase in the adjusted risk of PE.

Conclusion: Elevated D-dimers (>2590 ng·mL^-1) and absence of anticoagulant therapy predict PE in hospitalised COVID-19 patients with clinical signs of severity. These data strengthen the evidence base in favour of systematic anticoagulation, and suggest wider use of D-dimer guided CTPA to screen for PE in acutely ill hospitalised patients with COVID-19.

FIGURE 1

Flowchart of the study population. COVID-19: coronavirus disease 2019; S_pO2: oxygen saturation measured by pulse oximetry; CTPA: computed tomography pulmonary angiography; ICU: intensive care unit; PE: pulmonary embolism.

FIGURE 2

Computed tomography pulmonary angiography (CTPA) showing severe coronavirus disease 2019 (COVID-19) pattern and bilateral pulmonary embolism (PE). CTPA of a 54-year-old male with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 23 days after symptom onset and 17 days after admission to the intensive care unit. CTPA was performed because of severe hypoxaemia despite invasive mechanical ventilation, and showed, in addition to a severe COVID-19 computed tomography pattern, bilateral acute PE of segmental location. a) mediastinum window: presence of acute PE as a filling defect inside the left superior lobe pulmonary artery, segmental–subsegmental division of the lingula (red arrows); b) parenchymal window: COVID-19 CT pattern with peripheral ground-glass opacities associated with areas of consolidation.

FIGURE 3

Distribution of the different anticoagulant regimens in the whole study population and by group of patients with and without computed tomography pulmonary angiography-confirmed pulmonary embolism (PE).

FIGURE 4

Independent predictors of in-hospital computed tomography pulmonary angiography-confirmed pulmonary embolism (PE) in severe coronavirus disease 2019 (COVID-19) patients, using the Firth penalised likelihood estimator. a) Multivariable model including D-dimer analysed by quartile, D-dimer level (model fit: Akaike information criteria 99.1 and Bayes information criteria 133.1 for global model fit, and Harrell's C-statistic index 0.91 for discrimination). b) Multivariable model including D-dimer as a binary variable defined by receiver operating characteristic curve analysis (model fit: Akaike information criteria 104.6 and Bayes information criteria 138.4 for global model fit, and Harrell's C-statistic index 0.90 for discrimination).

FIGURE 5

Receiver operating characteristic curve identifying the cut-off value of D-dimer predictive of occurrence of pulmonary embolism. AUC: area under the curve.