Abstract 42: Chronic Endothelial Activation in Childhood Arterial Ischemic Stroke

Objective: Despite evidence suggesting that arterial inflammation plays a role in the pathophysiology of childhood arterial ischemic stroke (AIS), relatively little is known about inflammatory induced coagulation and/or endothelial activation. The object of this study was to compare biomarkers of coagulation activation [D-dimer and thrombin-antithrombin complex (TAT)] and endothelial activation [Plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor antigen (vWF Ag)] in children with AIS as compared to healthy pediatric controls. Methods: Sixty patients with childhood AIS (ages 28 days to 19 years) were enrolled in a prospective six-center study. Biomarker samples were collected in the acute (0-3 weeks post-AIS) and chronic (> 3 months post-AIS) timeframes. Healthy pediatric controls were enrolled at the central site. Biomarker differences by group were examined using t-test, chi-square, and, if demographics differed, regression models. Results: Age and gender were similar in all case and control groups, except age in acute vWF Ag and D-dimer populations [mean (SD): vWF Ag age = 9.3 yrs. (5.2), control age = 6.9 yrs. (4.3), P=0.007 ; D-Dimer age = 9.4 yrs. (5.2), control age = 7.3 yrs. (4.3), P=0.032 ]. All acute biomarkers were significantly elevated in cases as compared to healthy controls, while only markers of endothelial activation remained significantly elevated in cases during the chronic phase (PAI-1 P=0.0014 ; vWF Ag P=0.0002 ; Table). Conclusion: Children with AIS have increased levels of endothelial and coagulation activation during the acute phase following stroke, while endothelial biomarkers remain elevated beyond 3 months. These results suggest that endothelial activation persists into the chronic phase of childhood AIS. Future studies with larger cohorts and stroke subtype analysis are needed to evaluate the use of endothelial biomarkers as surrogates of ongoing disease and recurrence risk.