D-dimer Levels: What is Considered High?
A D-dimer level above 500 ng/mL (0.5 μg/mL) is generally considered elevated, though age-adjusted cutoffs should be used for patients over 50 years of age (age × 10 ng/mL) to improve specificity while maintaining high sensitivity for thrombotic events. 1, 2
Standard and Age-Adjusted D-dimer Cutoffs
- The conventional cutoff for D-dimer is 500 ng/mL (0.5 μg/mL), above which further diagnostic evaluation is typically warranted 1
- For patients over 50 years of age, an age-adjusted cutoff (age × 10 ng/mL) is recommended to improve specificity while maintaining sensitivity above 97% 1, 2
- The use of age-adjusted D-dimer cutoffs can increase the number of patients in whom pulmonary embolism (PE) can be safely excluded from 6.4% to 30% without additional false-negative findings 1
Clinical Context Affects D-dimer Interpretation
- D-dimer specificity decreases steadily with age, reaching as low as 10% in patients over 80 years old 1
- D-dimer levels are frequently elevated in patients with cancer, hospitalized patients, severe infections, inflammatory diseases, and during pregnancy 1
- During pregnancy, normal D-dimer levels progressively increase: 0.11-0.40 μg/mL in first trimester, 0.14-0.75 μg/mL in second trimester, and 0.16-1.3 μg/mL in third trimester (up to 2 μg/mL may still be normal) 2
Risk Stratification Based on D-dimer Levels
- The likelihood of pulmonary embolism increases with higher D-dimer levels 3, 4
- D-dimer levels above 2000 ng/mL with an unlikely clinical decision rule still carry a PE prevalence of 36% 3
- Extremely elevated D-dimer levels (>5000 ng/mL or >10× the cutoff) are highly specific for serious conditions including venous thromboembolism (VTE), sepsis, and/or cancer (89% of cases) 5
- D-dimer levels above 4000 ng/mL are associated with a very high PE prevalence, regardless of clinical decision rule score 3, 4
D-dimer in Clinical Decision Rules
- For patients with low clinical probability of PE who meet all 8 Pulmonary Embolism Rule-Out Criteria (PERC), D-dimer testing is not recommended 1
- For patients with low or intermediate pretest probability who don't meet PERC criteria, a normal D-dimer level (age-adjusted or <500 ng/mL) provides sufficient negative predictive value to exclude PE 1
- The YEARS clinical decision rule uses different D-dimer cutoffs based on clinical presentation: <1000 ng/mL for patients without clinical items and <500 ng/mL for patients with one or more clinical items 1, 6
Important Considerations and Limitations
- D-dimer has high sensitivity but low specificity for thrombotic events 2, 7
- Different D-dimer assays are not standardized and may yield different results, affecting diagnostic management 6
- Point-of-care D-dimer assays have lower sensitivity (88%) compared to laboratory-based tests (≥95%) and should only be used in patients with low pretest probability 1
- While a normal D-dimer level has high negative predictive value for excluding thrombosis, elevated levels require further diagnostic evaluation 2, 7
Clinical Application
- For suspected VTE with elevated D-dimer, appropriate imaging studies (compression ultrasonography for DVT or CT pulmonary angiography for PE) should be considered 2
- For suspected aortic pathology with D-dimer levels >0.5 μg/mL (sensitivity 94-100%), CT angiography should be considered 2
- The number of patients in whom D-dimer must be measured to exclude one PE increases from 3 in the general emergency department population to >10 in special populations (cancer, hospitalized patients, etc.) 1