From the Guidelines
No, D-dimer is not specific for pulmonary embolism (PE). While D-dimer is a useful screening test with high sensitivity for PE, it has poor specificity, meaning a positive result cannot confirm PE diagnosis 1. D-dimer is a fibrin degradation product that becomes elevated whenever there is significant clot formation and breakdown in the body. Many conditions besides PE can cause elevated D-dimer levels, including deep vein thrombosis, recent surgery, pregnancy, cancer, infection, inflammation, advanced age, and even normal aging.
Key Points
- The primary value of D-dimer testing is in its negative predictive value - a normal D-dimer level (typically <500 ng/mL, though thresholds may vary by laboratory and patient age) can help rule out PE in patients with low to moderate clinical probability 1.
- A positive D-dimer requires further diagnostic testing, usually with CT pulmonary angiography or ventilation-perfusion scanning, to confirm or exclude PE 1.
- D-dimer is considered a "rule-out" rather than a "rule-in" test for pulmonary embolism.
- Age-adjusted d-dimer thresholds (age × 10 ng/mL rather than a generic 500 ng/mL) can be used in patients older than 50 years to determine whether imaging is warranted 1.
Clinical Application
In clinical practice, D-dimer testing should be used in conjunction with clinical probability assessment to evaluate patients with suspected PE. The Pulmonary Embolism Rule-Out Criteria (PERC) can be applied to patients with low pretest probability of PE to decrease the use of d-dimer testing and imaging studies 1. However, D-dimer testing should not be relied upon as the sole diagnostic tool for PE, and further testing should be performed in patients with a high pretest probability of PE or in those with a positive D-dimer result.
From the Research
D-Dimer Specificity in Pulmonary Embolism (PE)
- The specificity of D-dimer for diagnosing pulmonary embolism (PE) is a topic of interest, with various studies providing insights into its utility and limitations.
- A study from 1993 2 found that the ELISA D-dimer assay had a specificity of 26% and 13% in all patients and those with non-high-probability V/Q scans, respectively, indicating low specificity.
- Another study from 2018 3 reported a specificity of 50.0% for D-dimer levels in diagnosing PE, using a threshold value of 1.3 µg/ml.
- The 2019 study 4 demonstrated that a combination of low clinical pretest probability and D-dimer levels can effectively rule out PE, but the specificity of D-dimer alone was not the primary focus.
- A narrative review from 2022 5 highlighted the potential pitfalls of D-dimer testing, including diagnostic errors and the impact of various factors on test results, which can affect specificity.
- A study from 2018 6 found that the high-sensitivity D-dimer had a specificity of 40.0% for diagnosing PE, with a negative likelihood ratio of 0.11, indicating that a negative result can help rule out PE, but a positive result has limited utility due to low specificity.
Factors Affecting D-Dimer Specificity
- Age, history of PE, recent surgery, and other clinical factors can elevate D-dimer levels, regardless of the presence of PE, which can affect specificity 6.
- The choice of assay and threshold values can also impact the specificity of D-dimer testing 2, 3.
- Clinical pretest probability assessment is essential in interpreting D-dimer results, as it can help adjust the threshold values and improve the specificity of the test 4.
Clinical Utility of D-Dimer
- Despite its limited specificity, D-dimer can be a useful tool in ruling out PE, particularly when combined with clinical pretest probability assessment and other diagnostic tests 2, 4, 6.
- The high sensitivity of D-dimer makes it a valuable screening tool, but its low specificity requires careful interpretation of results in the context of clinical presentation and other diagnostic findings 3, 5.