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Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis

BMJ 2014; 348 doi: (Published 10 March 2014) Cite this as: BMJ 2014;348:g1340
  1. G J Geersing, general practitioner1,
  2. N P A Zuithoff, statistician1,
  3. C Kearon, professor of medicine2,
  4. D R Anderson, professor of medicine3,
  5. A J ten Cate-Hoek, thrombosis specialist4,
  6. J L Elf, thrombosis specialist5,
  7. S M Bates, thrombosis specialist2,
  8. A W Hoes, professor of primary care and clinical epidemiology1,
  9. R A Kraaijenhagen, thrombosis specialist6,
  10. R Oudega, general practitioner1,
  11. R E G Schutgens, thrombosis specialist7,
  12. S M Stevens, thrombosis specialist8,
  13. S C Woller, thrombosis specialist8,
  14. P S Wells, professor of medicine9,
  15. K G M Moons, professor of clinical epidemiology1
  1. 1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, Netherlands
  2. 2Division of Haematology and Thromboembolism, Department of Medicine, McMaster University Hamilton, Hamilton, Canada
  3. 3Division of Haematology, Department of Medicine, Dalhousie University, Halifax, Canada
  4. 4Department of Internal Medicine, Maastricht University Medical Center, Maastricht, Netherlands
  5. 5Vascular Center, Skane University Hospital, Malmö, Sweden
  6. 6Department of Medicine, Academic Medical Center Amsterdam, Netherlands
  7. 7Van Creveld Clinic, University Medical Center Utrecht, Utrecht, Netherlands
  8. 8Thrombosis Clinic, Intermountain Medical Center, Murray, UT, USA
  9. 9Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada
  1. Correspondence to: G J Geersing g.j.geersing{at}
  • Accepted 28 January 2014


Objective To assess the accuracy of the Wells rule for excluding deep vein thrombosis and whether this accuracy applies to different subgroups of patients.

Design Meta-analysis of individual patient data.

Data sources Authors of 13 studies (n=10 002) provided their datasets, and these individual patient data were merged into one dataset.

Eligibility criteria Studies were eligible if they enrolled consecutive outpatients with suspected deep vein thrombosis, scored all variables of the Wells rule, and performed an appropriate reference standard.

Main outcome measures Multilevel logistic regression models, including an interaction term for each subgroup, were used to estimate differences in predicted probabilities of deep vein thrombosis by the Wells rule. In addition, D-dimer testing was added to assess differences in the ability to exclude deep vein thrombosis using an unlikely score on the Wells rule combined with a negative D-dimer test result.

Results Overall, increasing scores on the Wells rule were associated with an increasing probability of having deep vein thrombosis. Estimated probabilities were almost twofold higher in patients with cancer, in patients with suspected recurrent events, and (to a lesser extent) in males. An unlikely score on the Wells rule (≤1) combined with a negative D-dimer test result was associated with an extremely low probability of deep vein thrombosis (1.2%, 95% confidence interval 0.7% to 1.8%). This combination occurred in 29% (95% confidence interval 20% to 40%) of patients. These findings were consistent in subgroups defined by type of D-dimer assay (quantitative or qualitative), sex, and care setting (primary or hospital care). For patients with cancer, the combination of an unlikely score on the Wells rule and a negative D-dimer test result occurred in only 9% of patients and was associated with a 2.2% probability of deep vein thrombosis being present. In patients with suspected recurrent events, only the modified Wells rule (adding one point for the previous event) is safe.

Conclusion Combined with a negative D-dimer test result (both quantitative and qualitative), deep vein thrombosis can be excluded in patients with an unlikely score on the Wells rule. This finding is true for both sexes, as well as for patients presenting in primary and hospital care. In patients with cancer, the combination is neither safe nor efficient. For patients with suspected recurrent disease, one extra point should be added to the rule to enable a safe exclusion.


  • Contributors: GJG and KGMM wrote the first version of the manuscript. NPAZ and KGMM provided statistical expertise. All analyses were performed by GJG and supervised by KGMM. All authors provided intellectual content and critically revised the manuscript. GJG had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding: This study received no funding.

  • 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 required.

  • Data sharing: In this study individual patient data from 13 different studies are combined. Requests for data sharing can be sent to the first author of this paper (GJG), and are then discussed with all other coauthors.

  • Transparency: The lead author (GJG) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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