Do a low probability Wells score and a negative D-dimer (D-dimer) result rule out subacute pulmonary embolism (PE)?

Ruling Out Subacute Pulmonary Embolism with Wells Score and D-dimer

A low probability Wells score combined with a negative D-dimer test reliably rules out pulmonary embolism, including subacute PE, with a negative predictive value of approximately 99.5%. 1

Evidence Supporting This Approach

The combination of clinical probability assessment and D-dimer testing has been extensively validated for excluding PE:

• Studies demonstrate that patients with a low clinical probability (Wells score ≤4 points, "PE unlikely") and a negative D-dimer have a very low risk of PE during follow-up:
  • The Christopher Study found only 0.5% of patients with "PE unlikely" score and negative D-dimer developed venous thromboembolism during 3-month follow-up 1
  • Meta-analysis showed a negative predictive value of 99.7% (95% CI: 99.0-99.9%) for this combination 2
  • Wells' original validation found only 1 of 437 patients (0.2%) with low probability and negative D-dimer developed PE during follow-up 3

Diagnostic Algorithm for Suspected PE

1. Calculate Wells score to determine clinical probability:

   • Clinical symptoms of DVT (3.0 points)
   • No alternative diagnosis (3.0 points)
   • Heart rate >100 (1.5 points)
   • Immobilization or surgery in previous four weeks (1.5 points)
   • Previous DVT/PE (1.5 points)
   • Hemoptysis (1.0 point)
   • Malignancy (1.0 point)

2. Interpret Wells score:

   • ≤4 points: "PE unlikely"

   • 4 points: "PE likely"

3. D-dimer testing:

   • If "PE unlikely" and D-dimer negative: PE safely excluded (no further testing needed)
   • If "PE unlikely" and D-dimer positive: Proceed to imaging
   • If "PE likely": Proceed directly to imaging regardless of D-dimer result

Important Considerations

D-dimer Test Selection

• Highly sensitive quantitative assays (ELISA-based) should be used for patients with low or moderate pretest probability 1
• Moderate sensitivity qualitative assays should only be used for patients with low pretest probability 1

Age Adjustment

• D-dimer specificity decreases with age
• Consider age-adjusted D-dimer cutoffs (age × 10 μg/L above 50 years) to improve specificity while maintaining sensitivity 1

Limitations and Pitfalls

1. Subacute vs. Acute PE: The guidelines do not specifically differentiate between acute and subacute PE in terms of diagnostic approach. The same algorithm applies to both scenarios.

2. False Positive D-dimer Results: D-dimer is commonly elevated in:

   • Cancer patients
   • Hospitalized patients
   • Pregnant women
   • Post-surgical patients
   • Elderly patients

3. Clinical Judgment Component: The Wells score includes a subjective component ("alternative diagnosis less likely than PE"), which may affect standardization 1

4. Protocol Adherence: Studies show that when the diagnostic protocol is correctly followed, the risk of missed PE is extremely low (0.1% in one study) 3

Conclusion for Clinical Practice

For patients with suspected subacute PE, the combination of a low probability Wells score ("PE unlikely" ≤4 points) and a negative D-dimer test effectively rules out PE without the need for further imaging. This approach has been validated in multiple studies and is recommended in clinical guidelines 1.