Ranking of Confounding Variables Affecting Revised Geneva Score Specificity for PE
The most significant confounding variables affecting the specificity of the Revised Geneva Score for pulmonary embolism (PE) diagnosis, in order of magnitude of change, are: age >65 years, cancer, pregnancy, hospitalization status, and severe infection or inflammatory disease. 1
Detailed Ranking of Confounding Variables
1. Age >65 Years
- Most significant impact on specificity
- Specificity decreases steadily with age, dropping to approximately 10% in patients >80 years 1
- Age-adjusted D-dimer cut-offs (age × 10 μg/L for patients >50 years) have been developed specifically to address this issue
- Using age-adjusted cut-offs can increase the number of patients in whom PE can be excluded from 6.4% to 30% without additional false-negative findings 1
2. Active Cancer
- Significantly elevates D-dimer levels, reducing specificity 1
- Cancer patients have higher baseline D-dimer values even without PE
- Included as a specific item in the Revised Geneva Score (2 points in original version, 1 point in simplified version) 1
- Increases the "number needed to test" from 3 in general population to >10 1
3. Pregnancy
- Substantially reduces D-dimer specificity 1
- Standard clinical prediction rules (including Revised Geneva) perform poorly in pregnant women
- Requires specialized scoring systems like the Pregnancy-Adapted Geneva (PAG) Score 2, 3
- The PAG Score shows superior discriminative power (AUC of 0.795) compared to standard Revised Geneva Score (AUC of 0.684) in pregnant women 3
4. Hospitalization Status
- Inpatients have lower D-dimer specificity compared to outpatients or ED patients 1
- Comorbidities in the inpatient population contribute to elevated D-dimer levels 1
- Despite lower specificity, D-dimer testing remains appropriate for inpatients as it maintains high sensitivity 1
5. Severe Infection or Inflammatory Disease
- Significantly elevates D-dimer levels, reducing specificity 1
- Inflammatory processes activate coagulation and fibrinolysis pathways
- Increases the "number needed to test" from 3 in general population to >10 1
Clinical Implications and Adaptations
Modified Approaches for High-Risk Groups
For Elderly Patients:
- Use age-adjusted D-dimer cut-offs (age × 10 μg/L for patients >50 years)
- This approach maintains sensitivity >97% while significantly increasing specificity 1
For Cancer Patients:
- Consider lower threshold for advanced imaging
- Higher clinical suspicion is warranted even with borderline scores
For Pregnant Women:
For Hospitalized Patients:
- D-dimer testing remains appropriate despite lower specificity
- Consider lower threshold for imaging studies
Diagnostic Accuracy Considerations
- The simplified Revised Geneva Score (attributing 1 point to each variable) has similar diagnostic accuracy to the original version (AUC 0.74 vs. 0.75) 4
- When combined with age-adjusted D-dimer threshold and Revised Geneva Score at a cut-off of 5 points, diagnostic accuracy improves to 100% sensitivity, 61.7% specificity, and AUC of 0.87 5
- Using the Revised Geneva Score alone can rule out PE for more than half of all suspected cases without further imaging 5
Common Pitfalls to Avoid
- Applying standard D-dimer thresholds to elderly patients without age adjustment
- Using standard clinical prediction rules in pregnant women instead of pregnancy-adapted versions
- Overreliance on D-dimer testing in cancer patients, hospitalized patients, or those with inflammatory conditions
- Failure to recognize that the specificity of the Revised Geneva Score varies significantly across different patient populations
By understanding these confounding variables and their relative impact on the specificity of the Revised Geneva Score, clinicians can better interpret test results and make more appropriate diagnostic decisions for patients with suspected PE.