Fenômenos tromboinflamatórios na síndrome inflamatória multissistêmica pediátrica associada ao COVID-19: estudo multicêntrico no Rio de Janeiro

Abstract

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is associated with an increased risk of thrombosis, contributing to significant morbidity and mortality. Early identification of high-risk patients is essential to enable timely interventions and reduce thromboembolic complications. Objectives: To evaluate the frequency, clinical and laboratory manifestations, management, and risk factors for thromboembolism in patients with MIS-C, as well as to analyze mortality and develop a novel risk stratification score for thrombosis. Methods: This was a multicenter, bidirectional observational study including patients diagnosed with MIS-C according to CDC and WHO criteria. Risk factors for arterial and venous thrombotic events were identified, and a new risk stratification score was developed based on the WHO Progression Scale modified for MIS-C, incorporating a central venous catheter (CVC) as an additional variable. The discriminatory capacity of the score in predicting thrombotic risk was assessed using the receiver operating characteristic (ROC) curve, with the area under the curve (AUC) used to quantify its overall accuracy. The Youden index was applied to determine the optimal cutoff point, combining sensitivity and specificity to establish the most appropriate threshold for thrombosis risk stratification in MIS-C patients. Results: A total of 112 patients with MIS-C were included, of whom 59.9% were female, with a median age at diagnosis of 4.22 years. The case fatality rate in the study was 0.9%. Three patients developed thrombosis (66.6% female, median age 11.05 years). The observed thrombotic events were as follows: one patient with deep vein thrombosis (DVT) involving the common iliac vein, right iliac vein, and infrarenal inferior vena cava; one patient with arterial thrombosis (digital microvascular thrombosis); and one patient with CVC-associated DVT in the right internal jugular vein. The adapted risk score included the following criteria and respective points: CVC: 4 points, Myocarditis: 5 points, Giant coronary aneurysm: 5 points, Non-invasive ventilation: 6 points, Use of vasopressors: 8 points, Mechanical ventilation: 8 points, Dialysis: 9 points. The total score was 45 points, with a cutoff point of 23. At this threshold, the score demonstrated 66.67% sensitivity, 93.58% specificity, 22.22% positive predictive value (PPV), 99.03% negative predictive value (NPV), and 92.86% accuracy. Scores ≥ 23 were associated with a higher risk of thrombosis, whereas scores < 23 demonstrated a high capacity for thrombotic event exclusion, as evidenced by the high negative predictive value. Discussion: The case fatality rate (0.9%) observed in our study was significantly lower than the 6.76% national average, highlighting the impact of specialized management and high-quality care on MIS-C outcomes. The incidence of thromboembolic events in our cohort was 2.67%, lower than the 6.5% reported in multicenter studies. Literature data indicate that the frequency of thromboembolism in MIS-C ranges from 1.4% to 6.5%, with an increased risk in children aged ≥12 years, reaching up to 19% in this group. The lower incidence observed in our study may be related to the predominance of prepubertal patients, a group with a lower predisposition to thrombosis. Thrombotic events in MIS-C may include cerebral infarctions, intracardiac thromboses, and deep vein thrombosis, reinforcing the need for rigorous clinical surveillance and individualized thromboprophylaxis strategies. Conclusion: The developed risk score allows for early identification of MIS-C patients at risk for thrombosis, aiding in therapeutic decision-making and optimizing preventive interventions. Prospective and multicenter studies with larger cohorts must validate their clinical applicability and enhance their accuracy in risk stratification.