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

Willem M. Lijfering*, Jan-Leendert P. Brouwer, Nic J. G. M. Veeger, Ivan Bank, Michiel Coppens, Saskia Middeldorp, Karly Hamulyak, Martin H. Prins, Harry R. Bueller, Jan van der Meer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

168 Citations (Scopus)

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. (Blood. 2009; 113: 5314-5322)

Original languageEnglish
Pages (from-to)5314-5322
Number of pages9
JournalBlood
Volume113
Issue number21
DOIs
Publication statusPublished - 21-May-2009

Keywords

  • DEEP-VEIN THROMBOSIS
  • FACTOR-V-LEIDEN
  • ACTIVATED PROTEIN-C
  • ARTERIAL THROMBOSIS
  • PULMONARY-EMBOLISM
  • FACTOR-VIII
  • THROMBOEMBOLISM
  • MUTATION
  • DEFICIENCY
  • CARRIERS

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