Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis

Abstract

We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals. In answering questions raised regarding our study, we updated our database and repeated all analyses. Methods: We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first. Results: We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%). The median follow-up duration increased from 7 to 14 days. All patients received pharmacological thromboprophylaxis. The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%). The majority of thrombotic events were PE (65/75; 87%). In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92). Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4;. Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8). Conclusion:In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

CD147 (BSG) but notACE2expression is detectable in vascular endothelial cells within single cell RNA sequencing datasets derived from multiple tissues in healthy individuals

“…We read with interest the report of Varga et al (Varga et al 2020) showing endothelitis in association with viral inclusion bodies in endothelium from multiple organs of patients with coronavirus disease 2019 . This finding is of great relevance in view of multiple lines of evidence supporting a role for vascular endothelial dysfunction in the pathogenesis of COVID-19 including the presence of cardiovascular risk factors as an independent predictor of severe disease , the high incidence of thrombotic complications (Klok et al 2020) and the presence of coagulopathy (Tang et al 2020). An understanding of the mechanism of endothelitis may shed light on the diverse systemic manifestations of COVID-19 and suggest potential therapeutic approaches.…”

The renin–angiotensin system: An integrated view of lung disease and coagulopathy in COVID-19 and therapeutic implications

“…The increased TF in endothelial cells leads to thrombosis, which is present in numerous hospitalized COVID-19 patients (Bikdeli et al, 2020;Klok et al, 2020). The increased aldosterone may be responsible for the hypokalemia seen in many COVID-19 patients.…”

Transcriptional Profiling of Leukocytes in Critically Ill COVID19 Patients: Implications for Interferon Response and Coagulation

“…One of the key clinical features of COVID19 is upregulation of the pro-thrombotic phenotype and microvascular complications, leading to COVID19-associated coagulopathy (7). This is characterized by venous, arterial, and microvascular thrombosis despite the use of anti-coagulant therapies (32)(33)(34)(35)(36)(37)(38). Our study provides compelling evidence of COVID19 associated changes in coagulation-related gene expression levels that may exacerbate thrombosis caused by endothelial cell injury and platelet activation in COVID19+ ICU patients (7).…”