When should D-dimer (D-dimer assay) be used to rule out pulmonary embolism (PE)?

D-dimer Testing for Pulmonary Embolism: Evidence-Based Approach

D-dimer testing should be used to rule out pulmonary embolism (PE) only in patients with low or intermediate pretest probability, and should never be used in patients with high pretest probability of PE. 1

Clinical Probability Assessment: The Essential First Step

Before considering D-dimer testing, clinicians must first assess the pretest probability of PE using validated clinical prediction rules:

• Wells score - Widely validated and used
• Geneva score - Alternative validated tool
• Pulmonary Embolism Rule-Out Criteria (PERC) - For very low-risk patients

This assessment is crucial because the interpretation of D-dimer results depends entirely on pretest probability. The accuracy of clinical probability assessment, while modest, provides essential guidance for subsequent testing 2.

Algorithm for D-dimer Testing in Suspected PE

1. Low Pretest Probability Patients:

• If PERC negative (meet all 8 criteria): No D-dimer testing needed, PE safely ruled out 1
• If PERC positive (fail any criteria): Proceed to D-dimer testing
  • Negative D-dimer: PE ruled out
  • Positive D-dimer: Proceed to imaging (CTPA)

2. Intermediate Pretest Probability Patients:

• D-dimer testing is warranted
  • Negative D-dimer: PE ruled out
  • Positive D-dimer: Proceed to imaging (CTPA) 1

3. High Pretest Probability Patients:

• Do not use D-dimer testing - proceed directly to imaging
• A negative D-dimer in high-risk patients does not safely exclude PE 3
• CTPA is the preferred imaging method unless contraindicated 1

Age-Adjusted D-dimer Thresholds

For patients over 50 years, use age-adjusted D-dimer cutoffs:

• Age × 10 ng/mL rather than the standard 500 ng/mL cutoff
• This maintains sensitivity >97% while significantly improving specificity 1
• This approach is particularly valuable given the low specificity of D-dimer testing in elderly patients 4

Important Caveats and Pitfalls

1. Never skip clinical probability assessment

   • A normal D-dimer with a likely clinical probability still carries a 9.3% risk of PE 3
   • Clinical assessment must precede D-dimer interpretation

2. D-dimer has limited specificity in:

   • Hospitalized patients
   • Elderly patients
   • Cancer patients
   • Pregnant women 4

3. Only use highly sensitive D-dimer assays

   • ELISA and turbidimetric assays are preferred (sensitivity ~97%)
   • Latex agglutination assays have inadequate sensitivity (pooled ~70%) 1

4. Common practice errors to avoid:

   • Using D-dimer in high pretest probability patients
   • Proceeding to CT despite normal D-dimer in low/intermediate risk patients
   • Not proceeding to imaging after positive D-dimer 1

Evidence Quality Considerations

The American College of Physicians guidelines provide strong evidence for this approach, with a diagnostic pathway that has been prospectively validated 1. Studies consistently show that combining clinical probability assessment with D-dimer testing is safe and efficient, with a 3-month thromboembolic risk of 0% (95% CI, 0.0-5.6%) when PE is ruled out by this approach 2.

While some newer diagnostic approaches like V/Q SPECT show promise, they require further validation before implementation in routine clinical practice 5.