Safety profile of enhanced thromboprophylaxis strategies for critically ill COVID-19 patients during the first wave of the pandemic: observational report from 28 European intensive care units

Abstract

Introduction Critical illness from SARS-CoV-2 infection (COVID-19) is associated with a high burden of pulmonary embolism (PE) and thromboembolic events despite standard thromboprophylaxis. Available guidance is discordant, ranging from standard care to the use of therapeutic anticoagulation for enhanced thromboprophylaxis (ET). Local ET protocols have been empirically determined and are generally intermediate between standard prophylaxis and full anticoagulation. Concerns have been raised in regard to the potential risk of haemorrhage associated with therapeutic anticoagulation. This report describes the prevalence and safety of ET strategies in European Intensive Care Unit (ICUs) and their association with outcomes during the first wave of the COVID pandemic, with particular focus on haemorrhagic complications and ICU mortality. Methods Retrospective, observational, multi-centre study including adult critically ill COVID-19 patients. Anonymised data included demographics, clinical characteristics, thromboprophylaxis and/or anticoagulation treatment. Critical haemorrhage was defined as intracranial haemorrhage or bleeding requiring red blood cells transfusion. Survival was collected at ICU discharge. A multivariable mixed effects generalised linear model analysis matched for the propensity for receiving ET was constructed for both ICU mortality and critical haemorrhage. Results A total of 852 (79% male, age 66 [37–85] years) patients were included from 28 ICUs. Median body mass index and ICU length of stay were 27.7 (25.1–30.7) Kg/m2 and 13 (7–22) days, respectively. Thromboembolic events were reported in 146 patients (17.1%), of those 78 (9.2%) were PE. ICU mortality occurred in 335/852 (39.3%) patients. ET was used in 274 (32.1%) patients, and it was independently associated with significant reduction in ICU mortality (log odds = 0.64 [95% CIs 0.18–1.1; p = 0.0069]) but not an increased risk of critical haemorrhage (log odds = 0.187 [95%CI − 0.591 to − 0.964; p = 0.64]). Conclusions In a cohort of critically ill patients with a high prevalence of thromboembolic events, ET was associated with reduced ICU mortality without an increased burden of haemorrhagic complications. This study suggests ET strategies are safe and associated with favourable outcomes. Whilst full anticoagulation has been questioned for prophylaxis in these patients, our results suggest that there may nevertheless be a role for enhanced / intermediate levels of prophylaxis. Clinical trials investigating causal relationship between intermediate thromboprophylaxis and clinical outcomes are urgently needed.

Tracheostomy Timing and Outcome in Severe COVID-19: The WeanTrach Multicenter Study

“…Few studies investigated the type and rate of complications in the non-COVID-19 population. The impact of the time of tracheostomy on complications might be considered of great interest in COVID-19, as the time of disease represents a pivotal parameter to understand the hyperinflammatory state and coagulation disorders typical of certain stages of COVID-19 disease [ 39 , 40 ].…”

“…Tang et al reported tracheostoma bleeding as the leading complication [14 (17.5%)], with major bleeding occurring in 4 patients (5.0%) [ 25 ], but with a time to tracheostomy performance of 17.5 days. As abovementioned, this may be explained by the variety of clinical presentations of COVID-19 coagulopathy [ 39 , 40 ]. In fact, antithrombotic treatment and the natural history of the disease itself may lead to hemorrhagic or pro-coagulative complications, especially in the early phase, with an increase in pro-inflammatory cytokines, coagulation disorders, and endothelial and microvascular cell damage, that may be variable in timing and presentation [ 44 ].…”

The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication

“… 452 Consistently, in a cohort of critically ill COVID-19 patients with a high prevalence of thromboembolic events, enhanced thromboprophylaxis was associated with reduced ICU mortality without an increased hemorrhagic risk. 453 However, results from some other multicenter studies did not support routine empirical use of prophylactic anticoagulation in patients with COVID-19. 454 – 456 A retrospective analysis indicated that therapeutic anticoagulation was associated with lower mortality among hospitalized COVID-19 patients compared with prophylactic anticoagulation, although not statistically significant.…”

Kidney implications of SARS-CoV2 infection in children

“…Given the preponderance of evidence of SARS-CoV2 causing microthrombi and coagulation cascade abnormalities, there is growing evidence that adults infected with SARS-CoV2 can have thrombotic microangiopathy (TMA)-related changes in the kidney [ 33 , 34 ]. A propensity score-matched cohort analysis found anti-coagulation directed therapy to lower d-dimer levels had both lower mortality and AKI rates compared to standard of care [ 35 ].…”