From the Guidelines
The recommended D-dimer cutoff for excluding pulmonary embolism (PE) is an age-adjusted cutoff, where the cutoff value is calculated as age × 10 ng/mL for patients older than 50 years, as this approach maintains a sensitivity for PE above 97% while significantly increasing specificity. When using a non-age-adjusted cutoff, a value of less than 500 ng/mL is considered normal, but this may not be suitable for all patients, particularly older adults 1. The use of age-adjusted D-dimer cutoffs is supported by a meta-analysis of 13 studies and 12,497 patients, which found that this approach improved specificity without compromising sensitivity 1. Key points to consider when interpreting D-dimer results include:
- D-dimer levels rise naturally with age, so age-adjusted cutoffs are important for older patients
- D-dimer is only useful as a rule-out test when clinical probability is low or moderate
- Negative D-dimer results in low or moderate clinical probability contexts effectively exclude PE
- Elevated D-dimer levels should prompt imaging studies, regardless of clinical probability
- Clinical assessment and imaging studies should be considered when D-dimer is elevated or clinical suspicion remains high despite normal D-dimer levels.
From the Research
D-Dimer Cut-Off Values
The choice of D-dimer cut-off value is crucial in the diagnosis of venous thromboembolism (VTE) and other conditions. Several studies have investigated the optimal cut-off values for D-dimer testing.
- A study published in the American Journal of Hematology in 2019 2 discussed the properties of D-dimer as a biological marker of hemostatic abnormalities and its use in excluding the diagnosis of VTE.
- Another study published in The Netherlands Journal of Medicine in 2016 3 found that extremely elevated D-dimer levels (> 5000 μg/l) were associated with severe disease, including VTE, sepsis, and cancer.
Cut-Off Values for VTE Diagnosis
For the diagnosis of VTE, different cut-off values have been proposed:
- A study published in Thrombosis Research in 2022 4 compared the sensitivity and false negative rates of standard and age-adjusted D-dimer cut-offs for isolated distal DVT (IDDVT) and found that the false negative rate of the standard D-dimer cut-off was 2% for proximal DVT and 14.7% for IDDVT.
- A multicenter evaluation of a new quantitative highly sensitive D-dimer assay published in Thrombosis Research in 2010 5 reported a clinical cut-off for VTE at 500 ng/mL, with a sensitivity and negative predictive value (NPV) of 100% for all pretest probability subgroups.
- A study published in the Journal of Thrombosis and Haemostasis in 2021 6 compared the performance of different diagnostic strategies based on age-adjusted D-dimer cut-off levels and found that the strategy based on the age-adjusted cut-off level calculated by multiplying the patient's age by 10 above 50 years performed the best, with a higher specificity and NPV above 99%.
Age-Adjusted Cut-Off Levels
The use of age-adjusted cut-off levels has been proposed to improve the diagnostic accuracy of D-dimer testing:
- The study published in the Journal of Thrombosis and Haemostasis in 2021 6 found that the age-adjusted cut-off level was safe and cost-effective, with a reduction in diagnostic costs for pulmonary embolism and deep vein thrombosis.
- The study published in Thrombosis Research in 2022 4 found that the age-adjusted cut-off may be below the cut-off more frequently in subjects with IDDVT than standard cut-off D-dimer, although such D-dimer levels might exclude IDDVT that require treatment.