What is the next step if the D-dimer (D-dimer) level is elevated?

Management of Elevated D-dimer Levels

When D-dimer is elevated, the next step should be imaging with either proximal compression ultrasound (CUS) or computed tomographic pulmonary angiography (CTPA) based on the clinical probability of venous thromboembolism (VTE). 1

Diagnostic Algorithm Based on Clinical Probability

Low to Moderate Clinical Probability of VTE

1. Initial D-dimer testing

   • If D-dimer is negative: No further testing needed (safely excludes VTE) 1
   • If D-dimer is positive: Proceed to imaging 1

2. Imaging options when D-dimer is positive:

   • Proximal CUS (ultrasound of proximal leg veins)

     • If positive: Treat for DVT 1
     • If negative: Consider repeat CUS in 1 week or whole-leg ultrasound 1

   • Whole-leg ultrasound

     • If negative: No further testing needed 1
     • If positive for proximal DVT: Treat for DVT 1
     • If positive for isolated distal DVT: Consider serial testing to rule out proximal extension 1

   • CTPA (for suspected pulmonary embolism)

     • If positive: Treat for PE 1
     • If negative: No further testing needed (for MDCT) 1

High Clinical Probability of VTE

1. Proceed directly to imaging (D-dimer testing not recommended) 1
   • Either proximal CUS or whole-leg US for suspected DVT
   • CTPA for suspected PE

Special Considerations

Extremely Elevated D-dimer Levels

• D-dimer levels >5000 μg/L (>10x normal) are highly specific for serious conditions including VTE, sepsis, and/or cancer 2
• 89% of patients with extremely elevated D-dimer have a diagnosis of VTE, sepsis, and/or cancer 2
• The most common diagnoses with extremely elevated D-dimer are:
  • Pulmonary embolism (32%)
  • Cancer (29%)
  • Sepsis (24%)
  • Trauma/surgery (24%)
  • Deep vein thrombosis (13%) 2

Comorbid Conditions

• Initial testing with ultrasound may be preferred if the patient has comorbid conditions associated with elevated D-dimer levels 1
• In these cases, D-dimer testing has lower utility as patients are likely to have positive results even if VTE is absent 1

Imaging Challenges

• When ultrasound is impractical (e.g., leg casting, excessive subcutaneous tissue) or nondiagnostic, consider CT venography, MR venography, or MR direct thrombus imaging 1

Pitfalls to Avoid

1. Don't rely on D-dimer alone in high clinical probability cases

   • D-dimer has low negative predictive value in high-probability patients 1

2. Don't ignore extremely elevated D-dimer levels

   • Even if seemingly a solitary finding, maintain clinical suspicion for severe underlying disease 2

3. Consider false positives

   • D-dimer can be elevated in many conditions including:
     • Pregnancy
     • Advanced age
     • Recent surgery
     • Inflammation
     • Malignancy
     • Infection 3, 4

4. Don't overuse D-dimer testing in hospitalized patients

   • Lower utility in this population due to high prevalence of elevated results 1

5. Be aware of potential heterophilic antibody interference

   • Consider this when elevated D-dimer values don't match clinical presentation 5

By following this evidence-based approach to elevated D-dimer levels, clinicians can efficiently diagnose or exclude VTE while minimizing unnecessary testing and treatment.