title: Oral contraceptives and the absolute risk of venous thromboembolism in women with single or multiple thrombophilic defects: results from a retrospective family cohort study.
abstract: BACKGROUND
  The risk of venous thromboembolism (VTE) in women taking combined oral contraceptives (COCs) is attributed to changes in coagulation and fibrinolysis. Their impact may be greater in women with preexistent thrombophilic defects.
  
  
  METHODS
  We assessed the effects of COCs on absolute VTE risk in women with single or multiple thrombophilic defects in a retrospective family cohort study. Female relatives of probands with VTE and hereditary deficiencies of protein S, protein C, or antithrombin were tested for known thrombophilic defects, including the index deficiency. Absolute incidences of VTE were compared in deficient vs nondeficient women, in deficient and nondeficient women who ever or never used COCs, and in deficient and nondeficient women with 0, 1, or more than 1 other thrombophilic defect during exposure to COCs.
  
  
  RESULTS
  Of 222 women, 135 (61%) ever used COCs. Overall, annual incidences of VTE were 1.64% and 0.18% in deficient and nondeficient women, respectively; the adjusted relative risk was 11.9 (95% confidence interval, 3.9-36.2). The risk was comparable in deficient ever and never users (1.73% vs 1.54%). Annual incidences during actual COC use were 4.62% in deficient women and 0.48% in nondeficient women; the relative risk was 9.7 (95% confidence interval, 3.0-42.4). The incidence increased by concomitant thrombophilic defects, from 3.49% to 12.00% in deficient women and from 0% to 3.13% in nondeficient women.
  
  
  CONCLUSIONS
  Women with hereditary deficiencies of protein S, protein C, or antithrombin are at high risk of VTE during use of COCs, particularly when other thrombophilic defects are present. They have VTE at a younger age, but the overall risk is not increased by COCs.
authors.affiliation: Division of Haemostasis, Thrombosis and Rheology, Department of Hematology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands.
authors.forename: Elizabeth F W
authors.initials: EF
authors.lastname: van Vlijmen
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: Tom K A B
authors.initials: TK
authors.lastname: Eskes
authors.forename: Pieter A
authors.initials: PA
authors.lastname: de Graeff
authors.forename: Jan
authors.initials: J
authors.lastname: van der Meer
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015994:Incidence; D010375:Pedigree; D012189:Retrospective Studies; D018570:Risk Assessment; D013923:Thromboembolism / Q000453:epidemiology*; D019851:Thrombophilia / Q000150:complications* / Q000235:genetics*; D020246:Venous Thrombosis / Q000453:epidemiology*
chemical_list: D003277:Contraceptives, Oral, Combined