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Risk of recurrence after venous thromboembolism in men and women: patient level meta-analysis

BMJ 2011; 342 doi: (Published 24 February 2011) Cite this as: BMJ 2011;342:d813
  1. James Douketis, director of vascular medicine1, professor2,
  2. Alberto Tosetto, medical doctor3,
  3. Maura Marcucci, medical doctor4,
  4. Trevor Baglin, consultant haematologist5,
  5. Benilde Cosmi, medical doctor6,
  6. Mary Cushman, professor of medicine and pathology7,
  7. Paul Kyrle, professor8,
  8. Daniela Poli, medical doctor9,
  9. R Campbell Tait, consultant haematologist10,
  10. Alfonso Iorio, associate professor11
  1. 1St Joseph’s Healthcare Hamilton, Room F-544, 50 Charlton Avenue East, Hamilton, ON, Canada, L8N 4A6
  2. 2Department of Medicine, McMaster University, Hamilton
  3. 3Department of Hematology, San Bortolo Hospital, Vicenza, Italy
  4. 4Department of Internal Medicine, Internal and Vascular Medicine, University of Perugia, Perugia, Italy
  5. 5Department of Haematology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Trust, Cambridge, UK
  6. 6Department of Angiology and Blood Coagulation, University Hospital San Orsola-Malpighi, Bologna, Italy
  7. 7University of Vermont, Burlington, VT, USA
  8. 8Department of Medicine I, Medical University of Vienna, Vienna, Austria
  9. 9Thrombosis Centre, Department of Heart and Vessels, University Hospital Careggi, Florence, Italy
  10. 10Department of Haematology, Royal Infirmary, Glasgow, UK
  11. 11Departments of Medicine and Clinical Epidemiology and Biostatistics, McMaster University
  1. Correspondence to: J Douketis,  jdouket{at}
  • Accepted 21 December 2010


Objective To determine the effect of sex on the risk of recurrent venous thromboembolism in all patients and in patients with venous thromboembolism that was unprovoked or provoked (by non-hormonal factors).

Data source Comprehensive search of electronic databases (Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials) until July 2010, supplemented by review of conference abstracts and contact with content experts.

Study selection Seven prospective studies investigating an association between D-dimer, measured after anticoagulation was stopped, and disease recurrence in patients with venous thromboembolism.

Data extraction Patient level databases were obtained, transferred to a central database, checked, and completed with further information provided by authors.

Data synthesis 2554 patients with a first venous thromboembolism had follow-up for a mean of 27.1 (SD 19.6) months. The one year incidence of recurrent venous thromboembolism was 5.3% (95% confidence interval 4.1% to 6.7%) in women and 9.5% (7.9% to 11.4%) in men, and the three year incidence of recurrence was 9.1% (7.3% to 11.3%) in women and 19.7% (16.5% to 23.4%) in men. Among patients with unprovoked venous thromboembolism, men had a higher risk of recurrence than did women (hazard ratio 2.2, 95% confidence interval 1.7 to 2.8). After adjustment for women with hormone associated initial venous thromboembolism, the risk of recurrence remained higher in men (hazard ratio 1.8, 1.4 to 2.5). In patients with provoked venous thromboembolism, occurring after exposure to a major risk factor, recurrence of disease did not differ between men and women (hazard ratio 1.2, 0.6 to 2.4). In women with hormone associated venous thromboembolism and no other risk factors, recurrence was lower than that in women with unprovoked venous thromboembolism and no previous hormone use (hazard ratio 0.5, 0.3 to 0.8).

Conclusion In patients with a first unprovoked venous thromboembolism, men have a 2.2-fold higher risk of recurrent venous thromboembolism than do women, which remained 1.8-fold higher in men after adjustment for previous hormone associated venous thromboembolism in women. In patients with a first provoked venous thromboembolism, risk of recurrence does not differ between men and women with or without hormone associated venous thromboembolism. Indefinite anticoagulation may be given greater consideration in men than in women after a first venous thromboembolism.


  • We thank Clive Kearon and Shannon Bates for their review of this manuscript. The authors reported the following sources of funding for the studies included in this meta-analysis: FCSA (Federazione dei Centri di Sorveglianza e Monitoraggio della Terapie Antitrombotiche)cit_bcit_af ref_bf(Palareti, 2003 ref_num4924 / Palareti, 2006 #4925)ref_af; Oesterreichische Nationalbank (Jubilaeumsfonds), the Medizinisch-Wissenschaftlicher Fonds des Buergermeisters der Bundeshauptstadt Wien, and the Wiener Staedtische Versicherungcit_cit_af ref_bf(Eichinger, 2003 ref_num4923)ref_af; Chief Scientist Office, Scottish Executive Health Department (grant CZB/4/24)cit_cit_af ref_bf(Tait, 2007 ref_num4934)ref_af; HL-57951 and HL-58036 from the US National Heart, Lung, and Blood Institute.

  • Contributors: JD, AI, MM, and AT planned the study, developed the analysis plan, interpreted the study findings, and prepared and critically reviewed the manuscript. TB, BC, MC, PK, DP, and RCT provided the individual patient databases, interpreted the study findings, and critically reviewed the manuscript. JD and AI are the guarantors.

  • Funding: None.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not needed.

  • Data sharing: No additional data available.

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