Cardioembolic stroke in children and young adults: Comprehensive management and risk of hemorrhagic transformation-a single institutional experience

Abstract Background: Cardio-Embolic stroke affects up to 8 percent of children with congenital heart disease. Pediatric stroke guidelines recommend antithrombotic therapy (AT) in children with congenital heart disease at risk for stroke. These children are at high risk for hemorrhagic transformation (HT) of their stroke. In adults, the use of antithrombotic therapy after stroke is guided by risk for recurrent stroke and bleeding risk assessment. However, there is little such guidance for the pediatric population, and therapy plans are often adopted from systemic AT guidelines or adult randomized trials. Our study aims to describe the management of cardioembolic stroke in children and young adults at Nationwide Children's Hospital (NCH) and further characterize risk factors for HT. Objectives: This study aims to characterize timing of AT in children after cardioembolic stroke and its impact on outcomes. We also aim to identify risk factors for the development of HT in children and young adults, as well as the incidence of long term complications and stroke recurrence in this population. Methods: We conducted a retrospective study identifying term neonates to young adults (up to 21 years of age) with radiologically confirmed diagnosis of cardio-embolic stroke at NCH from 1/1/2014-1/1/2021. 91 patients were identified who met this criteria. A retrospective analysis was completed for demographic information, stroke characteristics, timing of anti-coagulation initiation, presence of hemorrhagic transformation, and risk factors associated with hemorrhagic transformation. Demographic characteristics and risk factors for hemorrhagic transformation were summarized using counts and percentages, stratified by the presence or absence of hemorrhagic transformation. Univariable and multivariable logistic regression were used to assess the timing of anticoagulation, risk factors for hemorrhagic transformation, and predictors of stroke recurrence in children and young adults with cardio-embolic stroke. Results were reported as odds ratios with 95% confidence intervals and corresponding p-values. Results: Of the 91 patients identified, 14 (15.38%) were found to have developed HT. Of these, 5 patients had HT identified prior to initiation of anti-coagulation. Within this cohort of 5 patients with initial HT at presentation, AT was started within a week of diagnosis and 2 patients had reported significant bleeding complications. There was not a significant difference in the odds of HT in patients for whom AT was initiated within 1 week compared to those who had AT started within 24 hours (OR = 1.02, 95% CI: 0.13–5.72, p = 0.98). Similarly, there was no significant difference between those initiating AT within 1 month compared to those initiating AT within 24 hours (OR = 1.28, 95% CI: 0.06-10.21, p = 0.83). Identified risk factors for hemorrhagic transformation in these patients includes a history of endocarditis (p < 0.01). The number of patients with long-term complications after initiation of AC was 16 (17.58%). These included bloody stools (25%), subdural hematoma (18.75%), intraparenchymal hemorrhage (18.75%). Conclusions: Risk of hemorrhagic transformation did not increase significantly depending on timing of AT initiation. Clinically significant risk factors for HT in this population include a recent history of cardiac catheterization, as well as prior anti-coagulation. Other notable risk factors include recent history of endocarditis and cardiopulmonary arrest prior to stroke diagnosis. Patients with these risk factors must be carefully considered when deciding the timing of initiation of anti-thrombotic therapy. Additionally, it is notable that patients who are started on long term anti-coagulation following diagnosis of cardio-embolic stroke require close ongoing monitoring, as many went on to develop bleeding side effects of these medications, even months after initiation.