title: Inherited thrombophilia in children with venous thromboembolism and the familial risk of thromboembolism: an observational study.
abstract: Screening for inherited thrombophilia (IT) is controversial; persons at high risk for venous thromboembolism (VTE) who benefit from screening need to be identified. We tested 533 first- and second-degree relatives of 206 pediatric VTE patients for IT (antithrombin, protein C, protein S, factor V G1691A, factor II G20210A) and determined the incidence of symptomatic VTE relative to their IT status. The risk for VTE was significantly increased among family members with, versus without, IT (hazard ratio = 7.6; 95% confidence interval [CI], 4.0-14.5; P < .001) and highest among carriers of antithrombin, protein C, or protein S deficiency (hazard ratio = 25.7; 95% CI, 12.2-54.2; P < .001). Annual incidences of VTE were 2.82% (95% CI, 1.63%-4.80%) among family members found to be carriers of antithrombin, protein C, or protein S deficiency, 0.42% (0.12%-0.53%) for factor II G202010A, 0.25% (0.12%-0.53%) for factor V G1691A, and 0.10% (0.06%-0.17%) in relatives with no IT. Given the high absolute risk of VTE in relatives with protein C, protein S, and antithrombin deficiency, we suggest screening for these forms of hereditary thrombophilia in children with VTE and their relatives. Interventional studies are required to assess whether thromboembolism can be prevented in this high-risk population.
authors.affiliation: Department of Pediatric Hematology/Oncology, Charité, Augustenburger Platz 1, Berlin, Germany. susanne.holzhauer@charite.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Holzhauer
authors.forename: Neil A
authors.initials: NA
authors.lastname: Goldenberg
authors.forename: Ralf
authors.initials: R
authors.lastname: Junker
authors.forename: Christine
authors.initials: C
authors.lastname: Heller
authors.forename: Monika
authors.initials: M
authors.lastname: Stoll
authors.forename: Daniela
authors.initials: D
authors.lastname: Manner
authors.forename: Rolf
authors.initials: R
authors.lastname: Mesters
authors.forename: Anne
authors.initials: A
authors.lastname: Krümpel
authors.forename: Michael
authors.initials: M
authors.lastname: Stach
authors.forename: Ulrike
authors.initials: U
authors.lastname: Nowak-Göttl
mesh_terms: D000375:Aging / Q000473:pathology; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D005858:Germany / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D012307:Risk Factors; D019851:Thrombophilia / Q000150:complications* / Q000453:epidemiology; D054556:Venous Thromboembolism / Q000150:complications* / Q000453:epidemiology