Thrombotic complications in children with Coronavirus disease 2019 and Multisystem Inflammatory Syndrome of Childhood

Coronavirus disease 2019 (COVID-19) associated coagulopathy is multifactorial and involves inflammation driven hypercoagulability, endothelial dysfunction, platelet activation, and impaired fibrinolysis. Hospitalized adults with COVID-19 are at an increased risk of both venous thromboembolism and ischemic stroke, resulting in adverse outcomes, including increased mortality. Although COVID-19 in children follows a less severe course, both arterial and venous thromboses have been reported in hospitalized children with COVID-19. Additionally, some children develop a postinfectious, hyperinflammatory illness termed multisystem inflammatory syndrome of childhood (MIS-C), which is also associated with hypercoagulability and thrombosis. Several randomized trials have evaluated the safety and efficacy of antithrombotic therapy in adults with COVID-19, although similar pediatric data are lacking. In this narrative review, we discuss the postulated pathophysiology of COVID-19 coagulopathy and summarize principal findings of the recently completed adult trials of antithrombotic therapy. We provide an up-to-date summary of pediatric studies investigating the rate of venous thromboembolism and ischemic stroke in COVID-19 and multisystem inflammatory syndrome of childhood in addition to reviewing the findings of the single, nonrandomized pediatric trial investigating the safety of prophylactic anticoagulation. Lastly, we outline adult and pediatric consensus guidelines on the use of antithrombotic therapy in this cohort. A detailed discussion of the practical implementation and current limitations of published data will hopefully address the knowledge deficits surrounding the use of antithrombotic therapy in children with COVID-19 and generate hypotheses for future research.