Abstract

factor VIII ◼ pulmonary embolism ◼ thrombosis ◼ von Willebrand factor W e report a case series of patients with coronavirus disease 2019 (CO-VID-19) with pulmonary embolism (PE) in our institution.Lille University Hospital is the tertiary care center for the North of France, the second greatest French region in population density (189 people per 1 km 2 ), also considered a metabolic area with high number of overweight patients.The study was approved by the institutional data protection authority of Lille University Hospital.Among the 107 first consecutive patients with confirmed COVID-19 admitted to the intensive care unit (ICU) for pneumonia from February 27 to March 31, we noticed an unexpectedly high number of PEs during their stay in the ICU: 22 (20.6%) at the time of analysis (April 9), within a median time from ICU admission of 6 days (range, 1-18 days).To determine whether this represents an increase in the expected incidence of PE over a similar time interval, we analyzed the files of 196 patients hospitalized in our ICU during the same time interval in 2019.Despite a similar severity score on admittance to the ICU, the frequency of PE in our CO-VID-19 series was twice as high as the frequency we found in this control period (20.6% versus 6.1%; absolute increased risk, 14.4% [95% CI, 6.1-22.8]).It was also twice as high as the 7.5% frequency of PE in the 40 patients with influenza admitted to the ICU between January 1 and December 30, 2019 (3 PEs; absolute increased risk, 13.1% [95% CI, 1.9-24.3]).A qualitative description of the main characteristics of the patients with PE in the different periods is given in the Table .Taking into account the ICU duration at time of analysis, we estimated the cumulative incidence of PE using the Kalbfleisch and Prentice method by taking into account death (n=15) and discharged alive (n=48) as competing events.The 22 patients still hospitalized in the ICU without PE at the time of analysis (median ICU length of stay, 15 days; range, 10-30 days) were treated as censored observations.At day 15 of ICU admission, the cumulative incidence of PE in patients with COVID-19 in the ICU was estimated to be 20.4% (95% CI, 13.1-28.7).In terms of the main data at ICU admission (using the univariable Fine and Gray model to estimate subhazard ratios of PE), D-dimers (estimate subhazard ratio per log-SD increase, 1.81 [95% CI,1.03-3.16]),plasma factor VIII activity (estimate subhazard ratio per log-SD increase,1.73 [95% CI, 1.10-2.72]),and von Willebrand factor antigen (estimate subhazard ratio per log-SD increase,1.69[95% CI, 1.12-2.56])values seem to be associated with a greater PE risk.At the time of PE diagnosis, 20 of 22 patients were receiving prophylactic antithrombotic treatment (unfractionated heparin or low-molecular-weight heparin) according to the current guidelines in critically ill patients. 1,2One patient with a history of deep venous thrombosis was receiving fluindione with an international normalized ratio in the therapeutic range, and 1 patient was receiving therapeutic unfractionated heparin because of atrial fibrillation.