Elevated α1-Antitrypsin Is a Risk Factor for Arterial Ischemic Stroke in Childhood.

α1-antitrypsin (α1-AT) is a physiological inhibitor of activated protein C (APC) and therefore decreased APC activity. APC itself causes an anticoagulant effect by inactivating factors Va and VIIIa. The present case-control study was performed to evaluate the role of the elevated α1-AT concentration in pediatric patients with ischemic stroke (IS). α1-AT concentrations were measured along with established prothrombotic risk factors 6–12 months after the acute thrombotic onset in 81 Caucasian children with IS aged 1 month to 18 years. The cutoff values defined as age-dependent 90th percentiles were obtained from 229 healthy controls. Median (range) values of α1-AT were significantly higher in patients compared with control subjects [122.0 mg/dl (61.4–224.0) vs. 114.0 mg/dl (66.8–156.0); p = 0.016]. In addition, 14 of the 81 patients (17.3%) compared with 10 of the 162 controls (6.2%) had α1-AT concentrations above the 90th age-dependent percentiles (p = 0.012). Multivariate analysis performed in a 1:2 matched case-control setting adjusted for the presence of established prothrombotic risk factors showed a significantly increased odds ratio (OR) and 95% confidence interval (CI) for patients with elevated α1-AT >90th percentiles and IS (OR/CI: 4.0/1.64–9.92; p = 0.0024). Data shown here give evidence that total α1-AT concentrations above the 90th age-dependent percentiles independently increase the risk of IS 4.0-fold in Caucasian children. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]