title: Role of reduced ADAMTS13 in arterial ischemic stroke: a pediatric cohort study.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Faculty of Medicine, University of Münster, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Lambers
authors.forename: Neil A
authors.initials: NA
authors.lastname: Goldenberg
authors.forename: Gili
authors.initials: G
authors.lastname: Kenet
authors.forename: Fenella J
authors.initials: FJ
authors.lastname: Kirkham
authors.forename: Daniela
authors.initials: D
authors.lastname: Manner
authors.forename: Timothy
authors.initials: T
authors.lastname: Bernard
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Mesters
authors.forename: Ralf
authors.initials: R
authors.lastname: Junker
authors.forename: Monika
authors.initials: M
authors.lastname: Stoll
authors.forename: Ulrike
authors.initials: U
authors.lastname: Nowak-Göttl
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology*; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000367:Age Factors; D002545:Brain Ischemia / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D011159:Population Surveillance / Q000379:methods; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human