Role of reduced ADAMTS13 in arterial ischemic stroke: A pediatric cohort study

Lambers, Moritz, Goldenberg, Neil A., Kenet, Gili, Kirkham, Fenella J., Manner, Daniela, Bernard, Timothy, Mesters, Rolf M., Junker, Ralf, Stoll, Monika and Nowak-Göttl, Ulrike (2013) Role of reduced ADAMTS13 in arterial ischemic stroke: A pediatric cohort study. Annals of Neurology, 73 (1), 58-64. (doi:10.1002/ana.23735).

Abstract

Objective: Previous studies in adults and mice have implicated ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), also known as von Willebrand factor (VWF)-cleaving protease, as a protective factor for stroke. Here we investigated ADAMTS13 in 208 pediatric patients with arterial ischemic stroke (AIS) and 125 population-based control children in a frequency-matched case-control study. Methods: The proportion of patients/controls with ADAMTS13 activity levels below and above the 10th percentile was compared. Additionally, in a quintile comparison, the proportion of patients versus controls in the lowest ADAMTS13 quintile was compared to those in the 2nd to 5th quintiles. Adjustment was performed for VWF antigen (VWF:Ag), factor VIII activity (FVIII:C), blood group, and age. Results: Forty-six of 208 patients (22%) showed ADAMTS13 levels below the 10th percentile, compared with 5 of 125 controls (4%; p < 0.001). Odds ratios/95% confidence intervals were 7.30/2.73-19.50 for the lowest percentile and 2.44/1.15-5.16 in the quintile comparison after adjustment for VWF:Ag, FVIII:C, blood group, and age. Comparing the proportion of patients with ADAMTS13 activity below the 10th percentile within the different stroke subtypes (undetermined, cardioembolic, steno-occlusive arteriopathies), no statistically significant differences were found (undetermined, 16 of 89; cardioembolic, 6 of 40; steno-occlusive arteriopathies, 24 of 79; p = 0.08). ADAMTS13 levels did not significantly differ among stroke subtypes (p = 0.29). Interpretation: Our findings implicate reduced ADAMTS13 activity as a risk factor for pediatric AIS, and support the concept that ADAMTS13 has a role in the pathogenesis of pediatric AIS.

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Contributors

Author: Fenella J. Kirkham

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