What is the normal reference range for D-dimer (D-dimer assay) levels?

Normal Reference Range for D-dimer

The normal reference range for D-dimer is generally considered to be less than 500 ng/mL (0.5 μg/mL or 0.5 mg/L FEU). 1

Understanding D-dimer Measurement

D-dimer is a fibrin degradation product formed when cross-linked fibrin is broken down by plasmin during fibrinolysis. Its primary clinical utility lies in its excellent negative predictive value for ruling out thromboembolic conditions.

Units and Reporting Variations

There are significant inconsistencies in how D-dimer results are reported:

• Unit types:

  • Fibrinogen Equivalent Units (FEU)
  • D-dimer Units (DDU)
  • FEU values are approximately twice as high as DDU values 2

• Unit magnitude variations:

  • ng/mL
  • μg/mL
  • mg/L
  • μg/L 2

• A survey revealed that 28 different combinations of measurement units are currently used for reporting D-dimer results 2

Cutoff Values and Sensitivity

• At 500 ng/mL (0.5 μg/mL):

  • Sensitivity: 98%
  • Specificity: 56% 1
  • Negative predictive value: 96-100% 1

• Sensitivity at different thresholds:

  • 0.1 μg/mL: 100% sensitivity

  • 0.5 μg/mL: 98% sensitivity

  • 0.9 μg/mL: 86% sensitivity 1

Clinical Significance of D-dimer Values

Normal Values

• Values below 500 ng/mL are generally considered normal and can safely exclude venous thromboembolism in patients with low clinical probability 2, 3

Borderline Values

• Values between 200-500 ng/mL in low-risk patients have a very low rate of confirmed VTE (0%; 95% CI 0%-0.6%) 4

Elevated Values

• Values >500 ng/mL may indicate various conditions including VTE, but have poor specificity
• Values >3.6 μg/mL are highly prognostic for deep vein thrombosis (sensitivity 93.8%, specificity 78.3%) 5

Extremely Elevated Values

• Values >50 mg/L FEU (>100 times the cutoff) are associated with serious conditions:
  • Venous thromboembolism (32% pulmonary embolism, 13% DVT)
  • Cancer (29%)
  • Sepsis (24%)
  • Trauma/surgery (24%)
  • Other conditions including massive bleeding, post-CPR status, DIC, and HELLP syndrome 6, 7

Important Considerations

Age-Adjusted Values

• D-dimer levels naturally increase with age, reducing specificity in older patients 2, 1
• Some guidelines recommend age-adjusted cutoffs for patients over 50 years (age × 10 ng/mL)

Factors Affecting D-dimer Levels

• Pregnancy
• Recent surgery or trauma (elevated for at least 14 days)
• Cancer
• Hospitalization
• Inflammation
• COVID-19 and other infections 2, 1

Limitations

• Poor specificity (many false positives)
• Different assay methods yield different results
• Cutoff values are not transferable between methods or institutions 2
• False negatives may occur with thrombosed false lumen, intramural hematoma, and chronic dissection (>2 weeks) 1

Remember that while a negative D-dimer (<500 ng/mL) is valuable for excluding thromboembolic disease in low-risk patients, positive results require further diagnostic evaluation due to the test's low specificity.