Thromboembolic complications in children with COVID-19 and MIS-C: A narrative review

Abstract

COVID-19 and multisystem inflammatory syndrome in children (MIS-C) have been associated with a higher incidence of hypercoagulability and thromboembolic events (TEs), even in children, leading to relevant morbidity, and mortality. However, our understanding of such complications in childhood is limited. To better understand the incidence, clinical manifestations, risk factors, and management of COVID-19 and MIS-C-related TEs in children, a review of the current literature and a brief update on pathophysiology are given. Sixty-two studies, describing 138 patients with TEs associated with COVID-19 or MIS-C, were included. The overall number of TEs was 157, as 16 patients developed multiple TEs: venous TEs represented the majority (54%), followed by arterial thrombosis (38%, mainly represented by arterial ischemic stroke-AIS), and intracardiac thrombosis (ICT) (8%). Within the venous TEs group, pulmonary embolism (PE) was the most frequent, followed by deep venous thrombosis, central venous sinus thrombosis, and splanchnic venous thrombosis. Notably, 10 patients had multiple types of venous TEs, and four had both venous and arterial thrombosis including a newborn. Most of them (79 cases,57%) had at least one predisposing condition, being obesity the most frequent (21%), especially in patients with PE, followed by malignancy (9%). In 35% of cases, no data about the outcome were available About one-third of cases recovered, 12% improved at discharge or follow-up, and 6% had persistent neurological sequelae. The mortality rate was 12%, with death due to comorbidities in most cases. Most fatalities occurred in patients with arterial thrombosis. Pediatricians should be aware of this life-threatening possibility facing children with SARS-CoV-2 infection or its multisystemic inflammatory complication, who abruptly develop neurological or respiratory impairment. A prompt intensive care is essential to avoid severe sequelae or even exitus.

Efficacy of sildenafil and high-dose anakinra in an MIS-C patient with pulmonary vasculitis: A case report

“…Diffuse vascular-endothelial damage is likely to play a major role in cases with severe cardiac and neurological involvement ( 15 , 19 – 22 ). The strong association between COVID-19 and coagulopathy suggests that multiple molecular pathways are involved and dysregulated through the disease progression, contributing to the development of thrombosis; this is true also for MIS-C ( 37 ). Endothelial dysfunction and barrier disruption lead to immune cell infiltration, and proinflammatory cytokine production, as well as thrombosis ( 38 ).…”

“…Recent studies in children have pointed to an increase in endothelial dysfunction markers in MIS-C, with a rise in soluble C5b-9 (which represents the activated product of the terminal complement cascade) and altered red blood cell morphology ( 39 , 40 ). In patients with MIS-C, high levels of fibrinogen and D-dimers increase the likelihood of a thrombotic state ( 37 ). As far as we know, our case represents the first report of pulmonary arterial hypertension (PAH) likely due to pulmonary vasculitis in a pediatric patient with MIS-C. We examined several explanations for the PAH in our young patient.…”

Thrombotic Events in MIS-C Patients: A Single Case Report and Literature Review

“…MIS-C patients are subjected to a hyperinflammatory state leading to a higher risk of thrombotic manifestations by the activation of the coagulation system, especially in the event of a more severe clinical course [ 7 , 8 , 10 , 50 , 51 , 52 ]. The incidence of TEs ranges from 1 to 6.5% in the largest series [ 3 , 10 , 21 , 50 , 51 ] and their occurrence is more frequent among adolescents, accounting for 7–19% in patients older than 12 years.…”

Circulating Serum Cystatin C as an Independent Risk Biomarker for Vascular Endothelial Dysfunction in Patients with COVID-19-Associated Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Observational Study

“…CV complications related to coronavirus disease 2019 (COVID-19) include, in addition to CV complications of hypercoagulable states, acute cardiac injury and inflammation [ 13 ]. Thrombotic complications are common with MIS-C, and patients with thrombotic complications have higher mortality [ 36 ]. Among the thrombotic complications, intracardiac thrombosis was demonstrated in one case in our cohort of MIS-C patients.…”