Role of reduced ADAMTS13 in arterial ischemic stroke: A Pediatric Cohort Study

Authors

  • Moritz Lambers MD,

    1. Faculty of Medicine, University of Münster, Münster, Germany
    2. Center of Thrombosis and Hemostasis, Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel, Germany
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  • Neil A. Goldenberg MD,

    1. Section of Hematology/Oncology/Bone Marrow Transplantation, Department of Pediatrics and the Mountain States Regional Hemophilia and Thrombosis Center, University of Colorado and Children's Hospital Colorado, Denver/Aurora, CO
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  • Gili Kenet MD,

    1. Thrombosis Unit, National Hemophilia Center, Sheba Medical Center, Tel-Hashomer and the Sackler Medical School, Tel Aviv University, Tel Aviv, Israel
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  • Fenella J. Kirkham MD,

    1. Neurosciences Unit, University College London Institute of Child Health, London, United Kingdom
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  • Daniela Manner MD,

    1. Center of Thrombosis and Hemostasis, Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel, Germany
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  • Timothy Bernard MD,

    1. Section of Child Neurology, Department of Pediatrics and the Mountain States Regional Hemophilia and Thrombosis Center, University of Colorado and Children's Hospital Colorado, Denver/Aurora, CO
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  • Rolf M. Mesters MD,

    1. Department of Internal Medicine, University Hospital of Münster, Münster, Germany
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  • Ralf Junker MD,

    1. Center of Thrombosis and Hemostasis, Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel, Germany
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  • Monika Stoll PhD,

    1. Genetic Epidemiology of Vascular Disorders, Leibniz-Institute for Arteriosclerosis Research at the University of Münster, Münster, Germany
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  • Ulrike Nowak-Göttl MD

    Corresponding author
    1. Faculty of Medicine, University of Münster, Münster, Germany
    2. Center of Thrombosis and Hemostasis, Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel, Germany
    • Center of Thrombosis and Hemostasis, Institute of Clinical Chemistry, University Hospital Kiel, Arnold-Heller-Str. 3, Building 17, 24105 Kiel, Germany
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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. ANN NEUROL 2013.

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