What further investigations are indicated when D-dimer (D-dimer) levels are elevated?

Further Investigations for Elevated D-dimer Levels

When D-dimer levels are elevated, further investigations should be directed toward ruling out venous thromboembolism (VTE), particularly deep vein thrombosis (DVT) or pulmonary embolism (PE), as these are the most common serious conditions associated with elevated D-dimer levels. 1

Diagnostic Approach Based on Clinical Probability

For Suspected DVT:

• Low Clinical Probability with Elevated D-dimer:

  • Proceed with compression ultrasonography (CUS) of the proximal veins 1
  • If CUS is negative, no further testing is needed 1

• Moderate Clinical Probability with Elevated D-dimer:

  • Perform proximal CUS or whole-leg ultrasonography 1
  • If proximal CUS is negative, repeat CUS in 1 week 1
  • If whole-leg US is negative, no further testing is required 1

• High Clinical Probability:

  • Proceed directly to proximal CUS or whole-leg ultrasonography regardless of D-dimer result 1
  • If proximal CUS is positive, treat for DVT without confirmatory venography 1
  • If isolated distal DVT is detected on whole-leg US, consider serial testing to rule out proximal extension 1

For Suspected Pulmonary Embolism:

• Non-High Risk PE (without shock or hypotension):

  • Proceed with CT pulmonary angiography (CTPA) 1
  • In centers where V/Q scintigraphy is readily available, it remains a valid option, particularly for younger patients and women to avoid unnecessary radiation 1

• High Risk PE (with shock or hypotension):

  • Proceed directly to CTPA if available and patient is stable 1
  • Consider bedside echocardiography in unstable patients 1

Special Considerations

• Extremely Elevated D-dimer Levels (>5000 μg/L):

  • Warrant thorough investigation as they are highly specific for serious illness 2
  • 89% of patients with extremely elevated D-dimer have VTE, sepsis, and/or cancer 2
  • Consider broader differential including:
    • Pulmonary embolism (32% of cases) 2
    • Cancer (29% of cases) 2
    • Sepsis (24% of cases) 2
    • Trauma/surgery (24% of cases) 2
    • Deep vein thrombosis (13% of cases) 2

• Renal Insufficiency:

  • D-dimer levels are often elevated in renal insufficiency regardless of VTE presence 3
  • Standard D-dimer cutoffs have high sensitivity but very low specificity in renal impairment 3
  • Consider direct imaging rather than D-dimer testing in patients with known renal insufficiency 3

• Suspected Aortic Dissection:

  • D-dimer has high sensitivity (94%) but variable specificity (40-100%) for acute aortic dissection 1
  • If clinical suspicion for aortic dissection exists, proceed directly to definitive imaging (CT angiography, MRI, or transesophageal echocardiography) regardless of D-dimer result 1
  • D-dimer should not be used to rule out aortic dissection in high-risk individuals 1

Important Caveats

• D-dimer should not be used as the sole guide for anticoagulation management decisions 1
• D-dimer has high sensitivity but poor specificity for VTE, especially in hospitalized patients, elderly, pregnancy, cancer, and inflammatory conditions 1, 4
• Initial testing with ultrasonography may be preferred over D-dimer in patients with comorbid conditions likely to cause elevated D-dimer levels even in the absence of VTE 1
• In patients with suspected upper extremity DVT and negative initial ultrasound but high clinical suspicion, consider further testing with D-dimer, serial ultrasound, or venographic-based imaging 1