Hemorrhagic transformation and stroke recurrence in children with cardiac disease receiving antithrombotic therapy for secondary stroke prevention

Abstract

Background: Antithrombotic therapy is currently recommended for stroke prevention in pediatric cardioembolic stroke where the recurrence risk is high; however, safety concerns remain. The primary objective of this study was to evaluate clinical and radiographic predictors of hemorrhagic transformation and stroke recurrence in children with cardiac disease to ascertain the safety and failure rates for secondary stroke prevention. Methods: This was a single-center, retrospective analysis of a prospectively enrolled cohort of children with radiologically confirmed cardioembolic stroke from January 2003 to December 2017 treated with institutional guidelines. Results: Eighty-two children met inclusion criteria (male 44 [54%]; neonates 23 [28%]; median age 0.43 years [0.08–4.23]). Hemorrhagic transformation occurred in 20 (24%) with the majority (75% of 20) being petechial and asymptomatic. One death (1%) was reported from hemorrhagic transformation. Four children (5%) had major extracranial hemorrhage. Most (95%) received antithrombic therapy, with anticoagulation being favored (82%). Greater stroke volume was associated with hemorrhagic transformation using the pediatric Alberta Stroke Program Early CT Score (6.1 ± 3.3 vs. 3.5 ± 2.3; p =.006). Stroke recurred in 11 (13%) children at a median 32 days (5.5–93) from the index event and the majority (90%) were on treatment at the time of recurrence. Children with univentricular physiology were less likely to have hemorrhagic transformation (RR 0.31; 95% CI 0.09–0.96, p =.04); however, they had higher rates of recurrent stroke before final palliative repair. Conclusions: In spite of the 24% hemorrhagic transformation rate, antithrombotic therapy has a positive risk-balance in certain cardioembolic stroke subgroups, particularly in those with single-ventricle physiology, when accounting for stroke volume.