The Wells rule was not useful in ruling out deep venous thrombosis in a primary care settingPDF
ACP J Club. 2006 Mar-Apr;144:47. doi:10.7326/ACPJC-2006-144-2-047
Related Content in this Issue
• Companion Abstract and Commentary: Review: The Wells rule is more useful than individual clinical features for predicting risk for deep venous thrombosis
Clinical Impact Ratings
Oudega R, Hoes AW, Moons KG. The Wells rule does not adequately rule out deep venous thrombosis in primary care patients. Ann Intern Med. 2005;143:100-7. [PubMed ID: 16027451]
In primary care patients with symptoms of deep venous thrombosis (DVT), how well does the Wells rule predict the presence or absence of DVT?
Design: A diagnostic rule developed by Wells and colleagues in a secondary care setting was evaluated in primary care patients.
Setting: Primary care practices of 110 physicians in the Netherlands.
Patients: 1295 patients > 18 years of age (mean age 60 y, 64% women), who visited their primary care physician with symptoms of swelling, redness, or pain in the legs ≤ 30 days and were suspected to have DVT. Patients with suspected pulmonary embolism were excluded.
Description of prediction guide: The Wells rule consisted of a score of 0 to 8, obtained by summing the presence of 8 characteristics identified from patient history (active cancer, immobilization of the leg, and recently bedridden) and physical examination (localized tenderness, whole leg or calf swelling, pitting edema, and collateral superficial veins), adjusted by −2 if another diagnosis was as or more likely than DVT. A score ≤ 0 indicated low risk, 1 to 2 indicated medium risk, and ≥ 3 indicated high risk. A normal result on D-dimer testing (< 500 ng/mL), combined with a low risk score on the Wells rule, indicated very low risk.
Outcomes: Sensitivity, specificity, negative predictive value, and negative likelihood ratio.
By the Wells rule, 39% of patients were categorized as being at low risk, 25% at medium risk, and 36% at high risk. Of patients in the low-risk group, 44% had a normal D-dimer test and were categorized as very low risk (17% of all patients). DVT was diagnosed by B-mode compression ultrasonography in 289 patients (22%): 12% of the low-risk group, 17% of the medium-risk group, and 37% of the high-risk group. 2.3% of patients in the very low-risk group had DVT. The diagnostic test properties, except specificity, improved when the D-dimer test was added to the Wells rule (Table).
In a primary care setting, the Wells rule was not useful for ruling out deep venous thrombosis in patients with symptoms. With the addition of the D-dimer test, sensitivity and negative predictive value increased, but specificity was poor.
Sources of funding: Healthcare Research Foundation “Ijsselmond” and The Netherlands Organization for Scientific Research.
For correspondence: Dr. R. Oudega, University Medical Center Utrecht, Utrecht, The Netherlands. E-mail email@example.com.
Table. Operating characteristics of the Wells rule, with and without the D-dimer test, for identifying primary care patients with deep venous thrombosis*
|Definition of a negative test||Sensitivity (95% CI)||Specificity (CI)||Negative predictive value (CI)||−LR (CI)|
|Wells score ≤ 0||79% (74 to 84)||44% (41 to 47)||88% (85 to 91)||0.48 (0.38 to 0.60)|
|Wells score ≤ 0 and normal D-dimer test||98% (97 to 100)||22% (19 to 24)||98% (96 to 100)||0.08 (0.03 to 0.19)|
*Diagnostic terms defined in Glossary.
Diagnosis of DVT is challenging because of its nonspecific clinical presentation. Recent research has focused on strategies to exclude the diagnosis of suspected DVT and reduce the use of expensive imaging tests. Many such strategies depend on a sensitive assay for D-dimer, a breakdown product of fibrin. Unfortunately, the D-dimer test has insufficient negative predictive value to safely “rule out” DVT on its own (1). Several studies have evaluated the usefulness of combining clinical pretest probability of disease and a sensitive D-dimer test to assess the safety of a low posttest probability of DVT to exclude the diagnosis.
Both physician empirical assessment (gestalt) and formalized clinical prediction guides (CPGs) have been tested. The best-known CPG, devised by Wells and colleagues, has been tested in many studies and has undergone several modifications. Using Wells' 9-point CPG, 3% of patients with a low score had DVT, corresponding to a −LR of 0.16 (2). Subsequent studies found that a negative D-dimer result in this group of patients refuted the diagnosis of DVT with a low rate of missed disease. These studies have been done mostly in emergency departments and specialty thrombosis clinics.
Goodacre and colleagues' meta-analysis of 51 such studies found that a low Wells score was associated with a −LR of 0.25, with better performance in patients without previous DVT (−LR 0.17) and when only proximal DVT was sought. The authors concluded that the −LR was low enough that addition of a negative sensitive D-dimer result was likely to safely exclude DVT. Interestingly, the authors also found that physician gestalt was associated with a −LR of 0.20, although this finding was based on only 4 studies and had a wide confidence interval.
The study by Oudega and colleagues offered contrasting results when the 9-point Wells score was used by primary care physicians, who received limited training in its application. The incidence of proximal DVT in the group with a low Wells score was 12%, compared with 3% in the Wells study (2) and 7% in the Goodacre meta-analysis, and the −LR was 0.48. When combined with a normal sensitive D-dimer result, the −LR fell to 0.08 (95% CI 0.03 to 0.19). In the population studied, this would correspond to a rate of missed DVT of up to 5.1%. If the data were reanalyzed to allow a Wells score ≤ 1 (corresponding to the more recent 2-category version of the CPG), the rate of missed disease could be as high as 5.6%.
A key challenge for the clinician in the interpretation of medical research is assessing external validity—how well do the results of a study apply to the patient at hand (3)? Oudega and colleagues suggested that the clinical setting accounts for the difference in outcome they observed, because of differences in patient population. Indeed, the population in the Oudega study was slightly older (mean age 60 y, compared with 57 y in the Wells study) and the results of the Goodacre meta-analysis suggested that the Wells score performed worse when the mean patient age was > 60 years (−LR 0.30 vs 0.24 in younger patients). However, it seems unlikely that this small age difference could account for so large a difference in outcome. Another explanation for the conflicting outcomes is that the Wells score is applied differently by different groups of physicians. Some features of the structured risk score, mostly related to physical examination, are prone to greater inter-individual variation. It is likely that the specific training in the application of the Wells score received by the physicians participating in the Oudega study, who were outside of an emergency department or specialty thrombosis setting, was not sufficient to develop adequate skills.
Because of the preponderance of evidence, the Wells score plus D-dimer test still serves as a good platform on which to base the workup of suspected DVT, especially in emergency departments and secondary care settings. Further research is needed, however, to evaluate the Wells score or an alternate CPG in primary care settings. A CPG-based strategy reduces the use of ultrasonography and other expensive tests and makes clinical decisions more objective. However, the algorithm alone cannot replace clinical judgment, as it might fail when applied to certain patients and in certain settings. The astute clinician who still suspects DVT in a patient with a low Wells score (especially a score of 1) and a negative D-dimer result will pursue further testing.
Scott M. Stevens, MD
LDS Hospital and University of Utah
Salt Lake City, Utah, USA
Walter Ageno, MD
University of Insubria
1. Goodacre S, Sampson FC, Sutton AJ, Mason S, Morris F. Variation in the diagnostic performance of D-dimer for suspected deep vein thrombosis. QJM. 2005;98:513-27. [PubMed ID: 15955795]
2. Wells PS, Anderson DR, Bormanis J, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet. 1997;350:1795-8. [PubMed ID: 9428249]
3. Hulley SB. Risk factors for coronary heart disease. Selected recent epidemiological advances. Drugs. 1988;36 Suppl 3:1-4. [PubMed ID: 3076113]