What is the role of D-dimer (D-dimer test) in diagnosing deep vein thrombosis (DVT) or pulmonary embolism (PE)?

Role of D-dimer in Diagnosing Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE)

D-dimer testing has high negative predictive value and should be used as a first-line test to rule out DVT or PE in patients with low clinical probability, but should always be combined with clinical probability assessment using validated clinical decision rules. 1

Diagnostic Value of D-dimer Testing

• D-dimer levels are elevated in plasma during acute thrombosis due to simultaneous activation of coagulation and fibrinolysis, making it valuable as a rule-out test 2
• D-dimer has high sensitivity (96%) but low specificity (35%) for venous thromboembolism (VTE), making it an excellent "rule-out" test but poor "rule-in" test 1
• A normal D-dimer level renders acute PE or DVT unlikely, while elevated D-dimer levels have low positive predictive value and cannot confirm PE 2
• Quantitative enzyme-linked immunosorbent assay (ELISA) or ELISA-derived assays have a diagnostic sensitivity of ≥95% 2

Clinical Decision Algorithm

Step 1: Assess Clinical Probability

• Use validated clinical decision rules such as the Wells score or revised Geneva score to stratify patients into low, intermediate, or high probability categories 2, 1
• The proportion of patients with confirmed PE is approximately 10% in low-probability, 30% in moderate-probability, and 65% in high-probability categories 2

Step 2: D-dimer Testing Based on Clinical Probability

• For patients with low clinical probability:

  • Start with a highly sensitive D-dimer test 1
  • If D-dimer is negative, no further testing is required (VTE is ruled out) 1
  • If D-dimer is positive, proceed to imaging 1

• For patients with intermediate or high clinical probability:

  • Consider proceeding directly to imaging without D-dimer testing 1
  • For suspected DVT, use proximal compression ultrasound or whole-leg ultrasound 1
  • For suspected PE, use CT pulmonary angiography 1

Special Considerations and Modifications

Age-Adjusted D-dimer Cut-offs

• D-dimer specificity decreases steadily with age to approximately 10% in patients >80 years 2
• For patients >50 years, use age-adjusted cut-off (age × 10 μg/L) to improve specificity while maintaining safety 2, 1
• Use of 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 2

Clinical Probability-Adjusted Cut-offs

• The "YEARS" clinical decision rule uses D-dimer thresholds adjusted based on clinical items:
  • For patients without clinical items: D-dimer <1000 ng/mL excludes PE
  • For patients with one or more clinical items: D-dimer <500 ng/mL excludes PE 2

Important Limitations and Pitfalls

• D-dimer has limited utility in certain populations where false positives are common:

  • Hospitalized patients 2, 1
  • Cancer patients 2, 1
  • Post-surgical patients 1
  • Pregnant women 2, 1
  • Patients with severe infection or inflammatory disease 2

• Never use a positive D-dimer alone to diagnose DVT or PE - confirmation with imaging is always required 1

• The negative predictive value of D-dimer is highest in patients with low clinical probability (99.5%) and lowest in those with high clinical probability (85.7%) 3

• The 3-month thromboembolic risk in patients with normal D-dimer and low/moderate clinical probability is approximately 0% (95% CI, 0.0-5.6%) 4

Clinical Effectiveness

• In outpatients with suspected PE, a negative ELISA D-dimer combined with clinical probability can exclude the disease without further testing in approximately 30% of patients 2
• Outcome studies show that the 3-month thromboembolic risk is <1% in patients with low or intermediate clinical probability who were left untreated based on a negative test result 2
• Different D-dimer assays have varying sensitivities and specificities, so clinicians should be aware of which assay is used at their institution 5