title: Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives.
abstract: Thrombophilia screening is controversial. In a retrospective family cohort, where probands had thrombosis and a thrombophilic defect, 2479 relatives were tested for thrombophilia. In antithrombin-, protein C-, and protein S-deficient relatives, annual incidences of venous thrombosis were 1.77% (95% CI, 1.14-2.60), 1.52% (95% CI, 1.06-2.11), and 1.90% (95% CI, 1.32-2.64), respectively, at a median age of 29 years and a positive family history of more than 20% symptomatic relatives. In relatives with factor V (FV) Leiden, prothrombin 20210G>A, or high FVIII levels, these were 0.49% (95% CI, 0.39-0.60), 0.34% (95% CI, 0.22-0.49), and 0.49% (95% CI, 0.41-0.51), respectively. High FIX, FXI, and TAFI, and hyperhomocysteinemia were not independent risk factors. Annual incidence of major bleeding in antithrombin-, protein C-, or protein S-deficient relatives on anticoagulants was 0.29% (95% CI, 0.03-1.04). Cumulative recurrence rates in relatives with antithrombin, protein C, or protein S deficiency were 19% at 2 years, 40% at 5 years, and 55% at 10 years. In relatives with FV Leiden, prothrombin 20210G>A, or high levels FVIII, these were 7%, 11%, and 25%, respectively. Considering its clinical implications, thrombophilia testing should address hereditary deficiencies of antithrombin, protein C, and protein S in patients with first venous thrombosis at young age and/or a strong family history of venous thrombosis.
authors.affiliation: Department of Hematology, University Medical Center Groningen, The Netherlands. w.lijfering@int.umcg.nl
authors.forename: Willem M
authors.initials: WM
authors.lastname: Lijfering
authors.forename: Jan-Leendert P
authors.initials: JL
authors.lastname: Brouwer
authors.forename: Nic J G M
authors.initials: NJ
authors.lastname: Veeger
authors.forename: Ivan
authors.initials: I
authors.lastname: Bank
authors.forename: Michiel
authors.initials: M
authors.lastname: Coppens
authors.forename: Saskia
authors.initials: S
authors.lastname: Middeldorp
authors.forename: Karly
authors.initials: K
authors.lastname: Hamulyák
authors.forename: Martin H
authors.initials: MH
authors.lastname: Prins
authors.forename: Harry R
authors.initials: HR
authors.lastname: Büller
authors.forename: Jan
authors.initials: J
authors.lastname: van der Meer
mesh_terms: D000328:Adult; D019774:Blood Coagulation Factor Inhibitors / Q000235:genetics; D001779:Blood Coagulation Factors / Q000235:genetics; D020147:Coagulation Protein Disorders / Q000235:genetics; D015331:Cohort Studies; D005192:Family Health; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D009426:Netherlands / Q000453:epidemiology; D012189:Retrospective Studies; D012306:Risk; D019851:Thrombophilia / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D020246:Venous Thrombosis / Q000097:blood / Q000453:epidemiology* / Q000209:etiology*
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors