Bleeding Risk Associated with Novel Oral Anticoagulants in Critically Ill Patients: A Scoping Review

Novel oral anticoagulants (NOACs) are widely used for the prevention and treatment of thromboembolic disease; nevertheless, critically ill patients were mostly excluded from the landmark randomized clinical trials. The purpose of this scoping review is to systematically map and synthesize the available evidence on bleeding risk associated with NOACs use in critically ill patients. Furthermore, we have also focused on ICU-specific risk factors, pathophysiological mechanisms and management strategies. Critical illness is characterized by dynamic pathophysiology, dysfunction of organs, and systemic inflammation that might change the exposure to anticoagulants and the risk of bleeding. A scoping review approach was utilized to synthesize findings of reviews, observational studies, clinical trials, and guideline documents on NOAC-associated bleeding. The focus was on populations related to critically ill units, such as patients with organ dysfunction, sepsis, malignancy, and invasive operations. The evidence summary was not conducted quantitatively. Bleeding is always prone to renal and hepatic dysfunction, old age, malignancy, polypharmacy, and concomitant antiplatelet treatment. The most clinically important manifestations of bleeding are the gastrointestinal and intracranial haemorrhages. The bleeding risk in critically ill patients receiving NOACs is highly heterogeneous and dynamic, with several patient- and illness-specific factors affecting the outcome, but current evidence is neither adequate nor tailored to capture heterogeneity across clinical contexts. Prospective studies of ICU-specific bleeding would better define bleeding risk and inform anticoagulation use and risk classification among this group.