key: cord-1022108-xj3jww6a authors: Tacquard, Charles; Mansour, Alexandre; Godon, Alexandre; Gruel, Yves; Susen, Sophie; Godier, Anne; Albaladejo, Pierre title: Anticoagulation in COVID-19: not strong for too long? date: 2021-03-30 journal: Anaesth Crit Care Pain Med DOI: 10.1016/j.accpm.2021.100857 sha: 2c0865fe0c46fd0ea5d23c475f3ca46bcfb8dcef doc_id: 1022108 cord_uid: xj3jww6a nan However, there are several critical points that need to be highlighted in this trial as they could limit the potential impact of these results on our daily clinical practice. First, composite end points must be taken with caution because they combine different elements that are not necessarily all related to the same end goal. The inclusion of the need for ECMO in the primary endpoint of this study is questionable, because the link between anticoagulation and the need for ECMO is not clearly established. A similar comment can be made about the multiplatform randomised trial (ATTAC, REMAP-CAP, and ACTIV-4) on therapeutic anticoagulation. The choice of 21-day organ support free days as the primary end point is questionable because organ failure in COVID-19 is multifactorial and the direct effect of anticoagulation on this end point may be diluted, which could lead to a false conclusion of futility. Only about 20% of the included patients underwent invasive ventilation, and the length of stay in the ICU was short, with a median of 6 [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] days, which is very different from the data observed in other ICU cohorts 2 . In addition, the mortality rate was strikingly high (42% of the study population), raising the question of a possible mismatch between needs and availability of ICU resources. The rate of thrombotic events in the standard-dose prophylactic anticoagulation group was very low, at 3.5%, which differed greatly from previously published studies on critically ill patients 3-5 (e.g., 27 .9% (95% CI 22.1-34.1) in the recent meta-analysis by Jimenez where patients were exposed to the assigned treatment for 20 days. Several studies have reported a significant risk of bleeding in patients with COVID-19, particularly in the most severe patients and in those on enhanced-dose anticoagulation [6] [7] [8] [9] . The longitudinal evaluation of haemostatic biomarkers showed that the procoagulant status of COVID-19 patients seems to be particularly marked during the first few days of hospitalisation and then gradually decreases to normal levels 10 . This raises the question of the temporal relationship between thrombosis and the bleeding risk, and whether these risks are concomitant or staggered in time. We performed a literature review of all studies on the thrombotic and bleeding risk associated with COVID-19. On the 5 th of March 2021, we searched MEDLINE and looked for studies on COVID-19 written in English that reported a median (or mean) duration and interquartile range -IQR -(or standard deviation -SD) between hospital or ICU admission and thrombotic or bleeding events. Case series with the time between admission and the event available were also included. Twenty-two studies were identified, thirteen of which specifically focusing on critically ill patients 3,7-9,11-28 . Thirteen studies reported only the time from admission to thrombotic events 3, [11] [12] [13] [14] [15] [16] [18] [19] [20] [21] 24 , four studies reported only the time from admission to bleeding events 8, [25] [26] [27] and five studies reported both 7, 9, 22, 23, 28 . One study analysed two different waves of patients 15 . All but two studies reported this delay as the median and interquartile range. 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