title: Impact of high-risk thrombophilia status on recurrence among children with a first non-central-venous-catheter-associated VTE: an observational multicentre cohort study.
abstract: Deficiency of antithrombin (AT), protein C (PC) or protein S (PS) constitutes a major risk factor for venous thromboembolism (VTE). Individuals at high risk for recurrence who benefit from screening need to be identified. The primary study objective was to determine the individual recurrence risk among children with a first non-central-venous-catheter-associated VTE with respect to their thrombophilia status and to evaluate if the clinical presentation at first VTE onset differs between children with AT, PC or PS deficiency versus no thrombophilia. We calculated the absolute risk of VTE recurrence and event-free-survival adjusted for thrombophilia, age, sex and positive family VTE history in 161 consecutively enrolled paediatric VTE patients. The presence of a deficiency relative to no thrombophilia was evaluated as a potential predictor of recurrence. Predictors for recurrence were AT deficiency (hazard ratio/95% CI: 6·5/2·46-17·2) and female gender (2·6/1·1-6·35). The annual recurrence rates (95% CIs) were 5·4% (2·6-10) in AT-deficient children, 1·3% (0·3-3·8) in patients with PC deficiency, 0·7% (0·08-2·4) in the PS-deficient cohort and 0·9% (0·4-1·8) in patients with no thrombophilia. Positive family VTE history or combined thrombophilias did not predict recurrence. Given the overall annual incidence rate of recurrence of 1·5% we suggest screening for AT deficiency in children with VTE.
authors.affiliation: Institute of Clinical Chemistry, University Hospital Kiel, Kiel, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Limperger
authors.affiliation: Thrombosis Unit, National Haemophilia Centre, Tel Hashomer and the Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Gili
authors.initials: G
authors.lastname: Kenet
authors.affiliation: All Children's Hospital Johns Hopkins Medicine and All Children's Research Institute, St. Petersburg, FL, USA.|Division of Hematology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Goldenberg
authors.affiliation: Department of Paediatric Haemostaseology, Frankfurt, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Heller
authors.affiliation: Department of Paediatric Haematology/Oncology, Charité, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Holzhauer
authors.affiliation: Institute of Clinical Chemistry, University Hospital Kiel, Kiel, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Junker
authors.affiliation: Institute of Clinical Chemistry, University Hospital Kiel, Kiel, Germany.
authors.forename: Ulrich C
authors.initials: UC
authors.lastname: Klostermeier
authors.affiliation: Department of Paediatric Haemostaseology, Dresden, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Knoefler
authors.affiliation: Department of Paediatrics, University Children Hospital Munich, Munich, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Kurnik
authors.affiliation: Department of Paediatric Haematology/Oncology, University Children Hospital Münster, Münster, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Krümpel
authors.affiliation: Department of Medicine/Haematology & Oncology, Univ. Hospital Münster, Münster, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Mesters
authors.affiliation: IT Service Centre, University Hospital of Münster, Münster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stach
authors.affiliation: Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Guy
authors.initials: G
authors.lastname: Young
authors.affiliation: Institute of Clinical Chemistry, University Hospital Kiel, Kiel, Germany. leagottl@uksh.de.|Department of Paediatric Haematology/Oncology, University Children Hospital Münster, Münster, Germany. leagottl@uksh.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Nowak-Göttl
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D019851:Thrombophilia / Q000150:complications*; D062666:Vascular Access Devices / Q000009:adverse effects*; D054556:Venous Thromboembolism / Q000453:epidemiology* / Q000209:etiology* / Q000401:mortality
keywords: antithrombin; children; protein C pathway; thrombophilia; thrombosis