Coagulopathy and thromboembolism in children with COVID-19 – pathophysiology, thrombotic risk, clinical manifestations and management

Abstract

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the beginning of the pandemic, it has been generally accepted that children infected with SARS-CoV-2 either stay asymptomatic or present benign symptoms. Yet SARS-CoV-2 is widely known to cause serious consequences in children and adolescents. Complications may develop during infection, several weeks afterwards, or in the course of multisystem inflammatory syndrome in children (MIS-C). MIS-C manifests with fever, gastrointestinal, cardiovascular and/or neurological symptoms. Moreover, thromboembolism is a relatively common complication of COVID-19 and MIS-C. The purpose of this work was to review current reports on thromboembolic complications among children who underwent SARS-CoV-2 infection. Among the published cases of MIS-C, thromboembolic incidents ranged from 1.4% to 6.5%, taking the form of a brain infarct, deep vein thrombosis, pulmonary embolism, or splenic infarct. Several mechanisms leading to thrombosis in COVID-19 in children are considered. The development of acute infection in the lungs results in local clot formation in the pulmonary microcirculation, leading to perfusion disturbances. ADAMTS13 activity is also mildly reduced in patients infected with SARS-CoV-2, increasing the risk of microthrombosis. COVID-19-associated coagulopathy is characterized by elevated D-dimers and fibrinogen levels. Significantly increased D-dimers probably represent activation of coagulation caused by viremia and cytokine storm, as well as possible organ dysfunction. The treatment of thromboembolism in children includes low and high molecular weight heparins and acetylsalicylic acid. Pediatricians should be aware of the possible multiple complications associated with COVID-19 in children, including thromboembolic incidents.