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.

Modeling severe functional impairment or death following ECPR in pediatric cardiac patients: Planning for an interventional trial.

AIM: We aimed to characterize extracorporeal CPR (ECPR) outcomes in our center and to model prediction of severe functional impairment or death at discharge. METHODS: All ECPR events between 2011 and 2019 were reviewed. The primary outcome measure was severe functional impairment or death at discharge (Functional Status Score [FSS] ≥ 16). Organ dysfunction was graded using the Pediatric Logistic Organ Dysfunction Score-2, neuroimaging using the modified Alberta Stroke Program Early Computed Tomography Score. Multivariable logistic regression was used to model FSS ≥ 16 at discharge. RESULTS: Of the 214 patients who underwent ECPR, 182 (median age 148 days, IQR 14-827) had an in-hospital cardiac arrest and congenital heart disease and were included in the analysis. Of the 110 patients who underwent neuroimaging, 52 (47%) had hypoxic-ischemic injury and 45 (41%) had hemorrhage. In-hospital mortality was 52% at discharge. Of these, 87% died from the withdrawal of life-sustaining therapies; severe neurologic injury was a contributing factor in the decision to withdraw life-sustaining therapies in 50%. The median FSS among survivors was 8 (IQR 6-8), and only one survivor had severe functional impairment. At 6 months, mortality was 57%, and the median FSS among survivors was 6 (IQR 6-8, n = 79). Predictive models identified FSS at admission, single ventricle physiology, extracorporeal membrane oxygenation (ECMO) duration, mean PELOD-2, and worst mASPECTS (or DWI-ASPECTS) as independent predictors of FSS ≥ 16 (AUC = 0.931) and at 6 months (AUC = 0.924). CONCLUSION: Mortality and functional impairment following ECPR in children remain high. It is possible to model severe functional impairment or death at discharge with high accuracy using daily post-ECPR data up to 28 days. This represents a prognostically valuable tool and may identify endpoints for future interventional trials.