title: Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis.
abstract: OBJECTIVE
  To assess the accuracy of the Wells rule for excluding deep vein thrombosis and whether this accuracy applies to different subgroups of patients.
  
  
  METHODS
  Meta-analysis of individual patient data.
  
  
  METHODS
  Authors of 13 studies (n = 10,002) provided their datasets, and these individual patient data were merged into one dataset.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Geersing
authors.forename: N P A
authors.initials: NP
authors.lastname: Zuithoff
authors.forename: C
authors.initials: C
authors.lastname: Kearon
authors.forename: D R
authors.initials: DR
authors.lastname: Anderson
authors.forename: A J
authors.initials: AJ
authors.lastname: Ten Cate-Hoek
authors.forename: J L
authors.initials: JL
authors.lastname: Elf
authors.forename: S M
authors.initials: SM
authors.lastname: Bates
authors.forename: A W
authors.initials: AW
authors.lastname: Hoes
authors.forename: R A
authors.initials: RA
authors.lastname: Kraaijenhagen
authors.forename: R
authors.initials: R
authors.lastname: Oudega
authors.forename: R E G
authors.initials: RE
authors.lastname: Schutgens
authors.forename: S M
authors.initials: SM
authors.lastname: Stevens
authors.forename: S C
authors.initials: SC
authors.lastname: Woller
authors.forename: P S
authors.initials: PS
authors.lastname: Wells
authors.forename: K G M
authors.initials: KG
authors.lastname: Moons
mesh_terms: D003937:Diagnosis, Differential; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D008487:Medical History Taking; D011237:Predictive Value of Tests; D011320:Primary Health Care / Q000379:methods*; D011336:Probability; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood / Q000175:diagnosis*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D