What to do with an elevated D-dimer (D-dimer) level in a patient without any clinical suspicion of pulmonary embolism (PE)?

Management of Elevated D-dimer Without Clinical Suspicion of Pulmonary Embolism

An elevated D-dimer without clinical suspicion of pulmonary embolism should not trigger further diagnostic imaging, as clinical probability assessment must always precede and guide the interpretation of D-dimer results.

Clinical Probability Assessment is Essential

• Clinical probability assessment using validated tools (Wells score, Geneva score) or clinician gestalt is the mandatory first step in evaluating suspected PE, not D-dimer testing 1
• D-dimer testing should only be performed after clinical probability has been assessed, as knowledge of D-dimer results before clinical assessment can inappropriately bias the clinician's assessment 2
• The European Society of Cardiology and American College of Physicians both emphasize that clinical probability stratification determines the subsequent testing strategy 1, 3

Proper Sequence for PE Evaluation

1. Clinical probability assessment first:

   • Low, intermediate, or high probability using validated tools 3
   • For low probability patients, apply PERC criteria (if all criteria met, no further testing needed) 3

2. D-dimer testing only after clinical assessment:

   • Only useful in patients with low or intermediate clinical probability 3
   • Not recommended in high clinical probability patients 3
   • Age-adjusted cutoffs (age × 10 ng/mL) should be used for patients >50 years 3

3. Imaging decisions based on combined assessment:

   • Normal D-dimer with low/intermediate probability: no imaging needed 3
   • Elevated D-dimer with low/intermediate probability: imaging warranted 3
   • High probability: proceed directly to imaging regardless of D-dimer 3

Pitfalls of Isolated D-dimer Testing

• D-dimer has high negative predictive value but poor positive predictive value (as low as 53%) 4
• The specificity of D-dimer decreases with age, dropping to only 10% in patients >80 years 1
• Ordering D-dimer without clinical suspicion leads to unnecessary imaging and potential harm 3
• When D-dimer is known before clinical assessment, physicians tend to inappropriately increase their clinical probability assessment 2

Management of Incidental Elevated D-dimer

• For patients with elevated D-dimer but no clinical suspicion of PE:

  • Perform a thorough clinical assessment using validated tools 3
  • If clinical probability is low and patient meets all PERC criteria, no further testing is needed 3
  • If clinical probability is low/intermediate but PERC criteria not met, consider alternative causes of elevated D-dimer 1
  • Only proceed to imaging if clinical assessment suggests PE is possible 3

• Common non-PE causes of elevated D-dimer:

  • Advanced age, pregnancy, recent surgery, trauma, malignancy, infection 1
  • These conditions may raise D-dimer without indicating PE 4

Safety Considerations

• The negative predictive value of a normal D-dimer with low clinical probability is excellent (99.5%) 5
• However, the negative predictive value decreases significantly with higher clinical probability (only 90.7% in patients with likely clinical probability) 6
• The 3-month thromboembolic risk in patients with normal D-dimer and low/moderate clinical probability is very low (0-0.6%) 5, 7

Key Practice Points

• Never order D-dimer without first assessing clinical probability 3, 1
• Never proceed directly to CTPA based solely on elevated D-dimer without clinical suspicion 3
• Clinical assessment should always guide interpretation of D-dimer results, not vice versa 2
• When D-dimer is elevated but clinical suspicion is absent, focus on clinical assessment rather than reflexively ordering imaging 1