title: Clinical and laboratory characteristics of paediatric and adolescent index cases with venous thromboembolism and antithrombin deficiency. An observational multicentre cohort study.
abstract: Venous thromboembolism [TE] is a multifactorial disease and antithrombin deficiency [ATD] constitutes a major risk factor. In the present study the prevalence of ATD and the clinical presentation at TE onset in a cohort of paediatric index cases are reported. In 319 unselected paediatric patients (0.1-18 years) from 313 families, recruited between July 1996 and December 2013, a comprehensive thrombophilia screening was performed along with recording of anamnestic data. 21 of 319 paediatric patients (6.6%), corresponding to 16 of 313 families (5.1%), were AT-deficient with confirmed underlying AT gene mutations. Mean age at first TE onset was 14 years (range 0.1 to 17). Thrombotic locations were renal veins (n=2), cerebral veins (n=5), deep veins (DVT) of the leg (n=9), DVT & pulmonary embolism (n=4) and pelvic veins (n=1). ATD co-occurred with the factor-V-Leiden mutation in one and the prothrombin G20210A mutation in two children. In 57.2% of patients a concomitant risk factor for TE was identified, whereas 42.8% of patients developed TE spontaneously. A second TE event within primarily healthy siblings occurred in three of 313 families and a third event among siblings was observed in one family. In an unselected cohort of paediatric patients with symptomatic TE, the prevalence of ATD adjusted for family status was 5.1%. 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: V
authors: V
authors: Limperger
authors: A
authors: A
authors: Franke
authors: G
authors: G
authors: Kenet
authors: S
authors: S
authors: Holzhauer
authors: V
authors: V
authors: Picard
authors: R
authors: R
authors: Junker
authors: C
authors: C
authors: Heller
authors: C
authors: C
authors: Gille
authors: D
authors: D
authors: Manner
authors: K
authors: K
authors: Kurnik
authors: R
authors: R
authors: Knoefler
authors: R
authors: R
authors: Mesters
authors: S
authors: S
authors: Halimeh
authors: 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: U
authors: U
authors: Nowak-Göttl
mesh_terms: D000293:Adolescent; D058833:Antithrombin Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005165:Factor V / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D010353:Patient Education as Topic; D015995:Prevalence; D011516:Prothrombin / Q000235:genetics; D012306:Risk; D019851:Thrombophilia / Q000453:epidemiology* / Q000235:genetics; D054556:Venous Thromboembolism / Q000453:epidemiology* / Q000235:genetics
chemical_list: D058833:Antithrombin Proteins; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin
keywords: Antithrombin deficiency; children; genetics