What are the causes of elevated D-dimer (D-dimer) levels?

Causes of Elevated D-dimer Levels

Elevated D-dimer levels are most commonly associated with venous thromboembolism (VTE), sepsis, and cancer, with extremely elevated levels (>5000 μg/L) being highly specific for these serious conditions. 1

Thrombotic Causes

• Venous thromboembolism (VTE):

  • Pulmonary embolism (PE) - one of the most common causes of significantly elevated D-dimer 2
  • Deep vein thrombosis (DVT) 2, 3
  • Cerebral venous thrombosis (CVT) 2

• Arterial thrombosis:

  • Myocardial infarction 2
  • Acute aortic dissection 2, 3

Non-thrombotic Causes

• Hematologic disorders:

  • Disseminated intravascular coagulation (DIC) 2, 3

• Inflammatory conditions:

  • Severe infections and sepsis 1
  • COVID-19 (associated with elevated levels that predict disease severity and mortality) 2
  • Acute respiratory distress syndrome (ARDS) 2
  • Acute exacerbation of COPD 4

• Other medical conditions:

  • Active malignancy 1, 3
  • Liver disease (due to impaired clearance) 2
  • Recent trauma or surgery 1, 5
  • Pregnancy (physiological increase, rising two- to fourfold by delivery) 2, 3

• Physiological factors:

  • Advanced age (natural increase with aging) 2, 3
  • Anxiety (typically causing mild elevations) 6

Clinical Significance of D-dimer Elevation

• D-dimer has high sensitivity but low specificity for thrombotic disorders 2
• Normal D-dimer has high negative predictive value for excluding VTE in low-risk patients 2, 5
• Extremely elevated D-dimer levels (>5000 μg/L) are highly specific (89%) for serious conditions including VTE, sepsis, and/or cancer 1
• Elevated D-dimer is independently associated with increased mortality across various disease states 7
• Persistent elevation after anticoagulation therapy indicates increased risk of recurrent thrombosis 2, 3

Special Considerations

• Age-adjusted cut-offs: The European Society of Cardiology recommends using age-adjusted D-dimer cut-offs (age × 10 μg/L) for patients over 50 years to improve specificity without compromising sensitivity 2

• Trauma patients: D-dimer remains elevated in severely injured patients for at least 48 hours after injury, limiting its diagnostic utility during this period 5

• Hospitalized patients: D-dimer testing has limited usefulness in hospitalized and acutely ill patients due to high frequency of false-positive results 2

• Magnitude of elevation: Consider the degree of D-dimer elevation when evaluating patients, as mild elevations may be attributable to less serious conditions like anxiety, while extreme elevations (>5000 μg/L) strongly suggest serious pathology 6, 1

• Clinical context: Never rely solely on D-dimer to rule out serious conditions if clinical suspicion is high 6