Thrombotic and hemorrhagic events in critically ill COVID-19 patients: a French monocenter retrospective study

Patients admitted to the intensive care unit (ICU) for coronavirus disease 2019 (COVID-19), following an infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seem to have an increased risk of thrombotic events (TE), both arterial and venous [1,2,3]. Even in the absence of high level of evidence, some centers have consequently modified their pharmacological thromboprophylaxis strategy toward intermediate or full-dose (therapeutic) preemptive anticoagulation (rather than prophylactic dosing) for routine care of COVID-19 patients [2, 4], exposing them to a higher risk of hemorrhagic events (HE).

Our aim was to assess the rates and to describe each TE and HE occurring in critically ill COVID-19 patients admitted to our ICU.

We retrospectively analyzed data from patients admitted to our 41-bed COVID-19 ICU between March 6 and April 22, 2020. All patients received usual (prophylactic) or full-dose (therapeutic) anticoagulation according to their risk factors for thrombosis [4]. All TE (venous or arterial) diagnosed during ICU stay were collected, except central venous catheter related thrombosis and hemodialysis filter thrombosis. TE were investigated only in case of clinical suspicion, and not in a routine manner. All significant (interruption of anticoagulation and red blood cell transfusion, surgical intervention or death) HE were collected.

During the study period, 92 patients were admitted to our ICU for acute respiratory failure related to SARS-CoV-2 pneumonia. Main demographic and clinical characteristics are detailed in the Table 1. At the time of analysis (May 6), 37 of them (40%) experienced a total of 39 TE including 31 venous (79%) and 8 arterial (21%) thrombosis, and 19 of them (21%) experienced a total of 22 HE during their ICU stay. Distributions of each TE and HE are detailed in the Fig. 1.

Description of thrombotic and hemorrhagic events among 92 critically ill COVID-19 patients

Full size image

Median days between ICU admission and TE and between first COVID-19 symptoms and TE were 9 [3–21] and 17 [12–28], respectively. There was no difference regarding clinical characteristics between patients with or without a TE, except from D-dimer levels and prothrombin time (Table 1). Among patients with an HE, 16 (n = 16/19, 84%) received full-dose anticoagulation, including 8 (50%) without a confirmed TE. All HE required interruption of anticoagulation, 3 (14%) were fatal 1 (2 intra-cranial, 1 deep muscle), 14 (64%) required red blood cells transfusion, and 5 (24%) required bronchoscopy or gastroscopy. Only one of the 15 (7%) anti-Xa activity performed the day of HE was overdosed.

We herein report on a 40% rate of TE in critically ill patients with COVID-19, mostly venous TE. This rate is in accordance with previous series [1, 2]. However, it is lower than the 69% rate reported by Llitjos et al. who performed a systematic screening with Doppler ultrasound [5]. As previously reported [2], PE was the leading cause of thrombosis in our cohort. As there is a growing interest in chest CT scan as a diagnostic tool for SARS-CoV-2 pneumonia [6], performing a systematic pulmonary angiography may constitute a relevant strategy.

Noteworthy, we report on a 21% rate of significant HE, most of them occurring in patients with full-dose anticoagulation. As half of these patients were treated with full-dose preemptive anticoagulation without a confirmed TE, we must be cautious about our thrombo-prophylaxis strategy with daily reassessment of its indication. Moreover, it is interesting to note that full-dose anticoagulation did not prevent some patients from developing a TE.

The retrospective monocenter design of our study implies numerous limitations. Nevertheless, we reported on a high rate of TE and HE in ICU COVID-19 patients highlighting the necessity to adapt our thrombo-prophylaxis strategy as well as our TE screening strategy.

The dataset used and analyzed for the current study is available from the corresponding author on reasonable request.

SOFA:

Sequential Organ Failure Assessment

SAPSII:

Simplified Acute Physiology Score II

None

No funding

Authors and Affiliations

1. Service de réanimation polyvalente, Centre Hospitalier Victor Dupouy, 69, rue du Lieutenant-Colonel Prud’hon, 95100, Argenteuil, France

   Megan Fraissé, Elsa Logre, Olivier Pajot, Hervé Mentec, Gaëtan Plantefève & Damien Contou

Contributions

MF, DC, and GP are responsible for the conception and design. All the authors were responsible for the data acquisition, analysis, and interpretation. All authors read, critically reviewed, and approved the final manuscript. DC takes responsibility for the paper as a whole.

Corresponding author

Correspondence to Damien Contou.

Ethics approval and consent to participate

This study was conducted in accordance with the amended Declaration of Helsinki and was approved by the Institutional Review Board (CE 20-39) of the French Intensive Care Society.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions