What is the role of D-dimer (D-dimer) in diagnosing and managing pulmonary embolism (PE)?

Role of D-dimer in Diagnosing and Managing Pulmonary Embolism

D-dimer testing is a valuable first-line tool for excluding pulmonary embolism (PE) in patients with low to intermediate clinical probability, but should not be used alone for diagnosis due to its high sensitivity but low specificity. 1

Clinical Probability Assessment and D-dimer Testing

Initial Approach

• Always begin with clinical probability assessment using validated tools (Wells criteria or Geneva score) before ordering D-dimer 1
• Clinical probability categories:
  • Low probability
  • Intermediate probability
  • High probability (or alternatively a two-level scheme: PE unlikely vs PE likely) 2

D-dimer Testing Strategy

• For patients with low clinical probability:

  • A negative D-dimer (<500 μg/L using ELISA method) safely excludes PE (negative predictive value >99%) 2, 3
  • No further testing needed if D-dimer is negative 2

• For patients with intermediate clinical probability:

  • A negative D-dimer using highly sensitive assays can exclude PE 1
  • Proceed to imaging if D-dimer is positive 2

• For patients with high clinical probability:

  • Skip D-dimer testing and proceed directly to imaging 2, 1
  • D-dimer has insufficient negative predictive value in this group 1

Diagnostic Performance of D-dimer

Sensitivity and Specificity

• ELISA D-dimer assays have sensitivity of 98-100% for PE 2
• Specificity is limited (40-46%) and decreases with age 2
• Rapid ELISA tests have similar sensitivity (100%) to classical ELISA 2
• Whole blood latex tests have lower sensitivity (87%) 2

Negative Predictive Value

• A normal D-dimer level has a negative predictive value of 91-99% 4, 3
• The 3-month thromboembolic risk after a negative D-dimer in appropriate patients is <1% 1, 5

Special Populations with Limited D-dimer Utility

D-dimer testing has reduced utility in certain populations due to frequent elevation from conditions other than PE:

• Hospitalized patients:

  • D-dimer excludes PE in <10% of hospitalized patients 2
  • Higher prevalence of conditions causing elevated D-dimer (infection, cancer, inflammation) 2

• Elderly patients:

  • Specificity decreases to only 10% in patients >80 years 2
  • Consider age-adjusted D-dimer cut-offs (age × 10 μg/L for patients >50 years) 2

• Pregnant patients:

  • Frequently elevated D-dimer levels limit specificity 1

• Cancer patients:

  • Higher D-dimer cut-off points may be needed (2,652 ng/mL) 6

Diagnostic Algorithm for Suspected PE

For Hemodynamically Stable Patients

1. Assess clinical probability of PE
2. If low/intermediate probability: Perform D-dimer test
   • If negative: PE excluded, no treatment needed
   • If positive: Proceed to imaging (CTPA)
3. If high probability: Skip D-dimer and proceed directly to CTPA 2

For Hemodynamically Unstable Patients

1. Bedside echocardiography is the most useful initial test
2. Evidence of right ventricular dysfunction suggests PE
3. Proceed to CTPA when patient is stabilized 2

Beyond Exclusion: Positive D-dimer Values

While D-dimer's primary role is in excluding PE, very high values may have some positive predictive value:

• D-dimer levels >2,152 ng/mL are associated with increased PE risk (PPV 53%) 6
• CTPA should be considered even for patients with low probability of PE when D-dimer values exceed four times the normal level 6

Common Pitfalls to Avoid

• Using D-dimer alone without clinical probability assessment 1, 5
• Relying on D-dimer in hospitalized patients where it has limited utility 2
• Using less sensitive D-dimer assays (like point-of-care tests) for patients with intermediate probability 2
• Failing to use age-adjusted cut-offs in elderly patients 2
• Interpreting positive D-dimer as diagnostic of PE (it requires confirmation) 4

D-dimer testing, when properly applied within diagnostic algorithms that include clinical probability assessment, significantly reduces the need for diagnostic imaging while maintaining safety in the evaluation of suspected PE.