title: Role of protein S deficiency in children with venous thromboembolism. An observational international cohort study.
abstract: Venous thromboembolism [TE] is a multifactorial disease, and protein S deficiency [PSD] constitutes a major risk factor. In the present study the prevalence of PSD and the clinical presentation at TE onset in a cohort of children is reported. In 367 unselected paediatric patients with TE (age 0.1-18 years) recruited between July 1996 and December 2013, a comprehensive thrombophilia screening was performed along with recording of anamnestic data. Thirty of 367 paediatric patients (8.2 %) derived from 27 families had PSD. Mean age at first TE onset was 14.5 years (range 0.1 to 18). Thrombotic locations were cerebral veins (n=8), calf vein TE (n=3) deep veins (DVT) of the leg (n=12), DVT & pulmonary embolism (n=5) and intra-cardiac veins (n=1) or purpura fulminans (n=1). PSD co-occurred with the factor 5 mutation at rs6025 or the homozygous factor 2 susceptibility variant at rs1799963 in one case each. The Heerlen polymorphism detected in five children presented with milder PSD. In 18 patients (60 %) a concomitant risk factor for TE was identified. A second TE event within primarily healthy siblings occurred in three of 27 PSD families (11.0 %). In this cohort of children with symptomatic TE, the prevalence of PSD adjusted for family status was 7.4 %. Given its clinical implication for patients and family members, thrombophilia testing should be performed and the benefit of medical or educational interventions should be evaluated in this high-risk population.
authors.forename: Ulrich C
authors.initials: UC
authors.lastname: Klostermeier
authors.forename: Verena
authors.initials: V
authors.lastname: Limperger
authors.forename: Gili
authors.initials: G
authors.lastname: Kenet
authors.forename: Karin
authors.initials: K
authors.lastname: Kurnik
authors.forename: Martine
authors.initials: M
authors.lastname: Alhenc Gelas
authors.forename: Ulrich
authors.initials: U
authors.lastname: Finckh
authors.forename: Ralf
authors.initials: R
authors.lastname: Junker
authors.forename: Christine
authors.initials: C
authors.lastname: Heller
authors.forename: Barbara
authors.initials: B
authors.lastname: Zieger
authors.forename: Ralf
authors.initials: R
authors.lastname: Knöfler
authors.forename: Susanne
authors.initials: S
authors.lastname: Holzhauer
authors.forename: Rolf
authors.initials: R
authors.lastname: Mesters
authors.forename: Anne
authors.initials: A
authors.lastname: Krümpel
authors.affiliation: Ulrike Nowak-Göttl, Center of Thrombosis & Hemostasis, Institute of Clinical Chemistry, Univ.Hospital Kiel, Arnold-Heller-Str. 3, building 17, 24105 Kiel, Germany, E-mail: leagottl@uksh.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Nowak-Göttl
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D038622:Internationality; D008297:Male; D009154:Mutation; D010372:Pediatrics; D011110:Polymorphism, Genetic; D015995:Prevalence; D018455:Protein S Deficiency / Q000097:blood* / Q000150:complications / Q000235:genetics*; D012307:Risk Factors; D019851:Thrombophilia; D013927:Thrombosis / Q000503:physiopathology; D054556:Venous Thromboembolism / Q000097:blood* / Q000150:complications
keywords: Protein S deficiency; children; genetics