key: cord-0993732-9u49trc2
authors: Voicu, Sebastian; Bonnin, Philippe; Stépanian, Alain; Chousterman, Benjamin G.; Le Gall, Arthur; Malissin, Isabelle; Deye, Nicolas; Siguret, Virgine; Mebazaa, Alexandre; Mégarbane, Bruno
title: High prevalence of deep vein thrombosis in mechanically ventilated COVID-19 patients
date: 2020-05-30
journal: J Am Coll Cardiol
DOI: 10.1016/j.jacc.2020.05.053
sha: a31a8cd413ad87c51f7753d4c71cf0c01d0e8180
doc_id: 993732
cord_uid: 9u49trc2

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SARS-CoV-2 pneumonia patients present with coagulation disorders and marked susceptibility to thrombosis (1, 2) . However, the exact prevalence of DVT has been poorly investigated while the risk seems increased in ICU patients (3) . Therefore, we decided to perform routine duplex ultrasound examination of the lower limb veins systematically, in order to administer appropriate anticoagulation in all intubated and mechanically ventilated patients with SARS-CoV-2 pneumonia.

We conducted a prospective observational study in the medical and surgical critical care departments of Lariboisière University Hospital, Paris, France. Consecutive adults receiving invasive mechanical ventilation for SARS-CoV-2 pneumonia were included. Patients with previously diagnosed DVT or pulmonary embolism were excluded. During the hospital stay, prophylactic anticoagulation was administered as daily subcutaneous 4,000IU enoxaparin and, if glomerular filtration rate <15mL/min, as continuous intravenous infusion of daily 15,000IU unfractionated heparin. Duplex ultrasonography and plasma D-dimer assessment (STA-Liatest-DDI-Plus ® , Stago, France) were performed in all patients during the first week of ICU admission. In patients without DVT on the initial ultrasound, a second ultrasound examination was performed ~7 days later. Quantitative variables are expressed as medians [25 th -75 th percentiles] and categorical variables as percentages. The study was part of the French COVID-19 cohort registry and was approved by our institutional ethics committee (IDRCB, 2020-A00256-33; CPP, 11-20 20.02.04.68737). When possible, signed informed consent was obtained from the patients or the next of kin.

From March 13 th to April 3 rd 2020, fifty-six patients with SARS-CoV-2 pneumonia were included. Most of the patients were male (75%), with hypertension (46%), diabetes (45%), obesity (30%) and ischemic heart disease (20%). They required vasopressors in 32% of the cases. Prophylactic anticoagulation using enoxaparin or unfractionated heparin was administered in 41 patients (73%) and eight patients (14%), respectively. Therapeutic anticoagulation was used in seven patients (13%) to treat atrial fibrillation (N=2) and manage extracorporeal membrane oxygenation (N=5).

The initial ultrasound was performed 3 days [2] [3] [4] Studies have reported a highly variable prevalence of DVT, between 2.0 (2) and 14.8% (3) in ICU patients, most likely due to the absence of consistent screening. To the best of our knowledge, this is the first study performing systematic ultrasound examination for DVT diagnosis, thus providing data free of selection biases. Our data showed a remarkably high DVT prevalence (46%) and revealed the rapid time-course of thrombus formation despite prophylactic anticoagulation. Importantly, 50% of the DVT were popliteal or femoral, these being most often associated with thromboembolic events, consistent with the unexpectedly high number of pulmonary embolisms (21%) reported in SARS-CoV-2 pneumonia patients admitted to the ICU Our data suggests that close monitoring of DVT occurrence is necessary in mechanically ventilated SARS-CoV-2 patients, and since ultrasound may not always be available especially in epidemic settings, larger studies may investigate the diagnostic performance of D-dimers for DVT diagnosis in these patients. Moreover, the intensity of anticoagulation may need to be reconsidered based on future investigations to ensure more effective prevention (1) .

In conclusion, we demonstrated a very high DVT prevalence including a high proportion of potentially life-threatening proximal DVT in mechanically ventilated SARS-CoV-2 patients despite standard prophylactic anticoagulant treatment, suggesting the need for close DVT monitoring and assessment of the risks/benefits of more intense anticoagulation regimens in this population. 

COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up

High risk of thrombosis in patients with severe SARS

CoV-2 infection: a multicenter prospective cohort study

Thrombotic events in SARS-CoV-2 patients: an urgent call for ultrasound screening

Pulmonary Embolism in COVID-19 Patients: Awareness of an Increased Prevalence

The authors would like to thank Marie Neuwirth, Maxime Delrue, Caroline Grant and Edwige Matera for helping with data gathering and Siemens Healthineers France for kindly lending Lariboisière hospital ultrasound machines for the duration of the pandemic. The authors would also like to thank Mrs. Alison Good (Scotland, UK) for her helpful review of the manuscript.