Thrombotic Complications in Children with COVID-19 and MIS-C

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 thrombo-embolism (VTE) and ischemic stroke, resulting in adverse outcomes including mortality. While children with COVID-19 follow a less severe course, both arterial and venous thrombosis have been reported in hospitalized children with COVID-19. Additionally, some children develop a post-infectious, hyper-inflammatory 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, though 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 VTE and ischemic stroke in COVID-19 and MIS-C, in addition to reviewing the findings of the single, non-randomized pediatric trial investigating the safety of prophylactic anticoagulation. Lastly, we outline the 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 knowledge deficits surrounding the use of antithrombotic therapy in children with COVID-19, and generate hypotheses for future research.