From the Guidelines
Elevated D-dimer levels with a negative pulmonary embolism evaluation are most likely due to an alternative diagnosis, such as infections, inflammation, or cancer, rather than a false positive, and thus require further investigation to identify and treat the underlying cause. When interpreting an elevated D-dimer in the context of a negative pulmonary embolism (PE) evaluation, it is crucial to consider the low positive predictive value of D-dimer testing, as outlined in the 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism 1. D-dimer levels are elevated in plasma in the presence of acute thrombosis but also in conditions like cancer, severe infection, inflammatory disease, and during pregnancy, which makes it essential to look beyond PE for the cause of elevation. The management of such patients should focus on:
- Identifying the underlying cause of the elevated D-dimer through additional workup, which may include a complete blood count, comprehensive metabolic panel, inflammatory markers, and targeted testing based on symptoms.
- Treating the identified condition, as no specific medication is needed to treat the elevated D-dimer itself. It's also important to note that D-dimer has excellent sensitivity but poor specificity for PE, making it valuable as a rule-out test but not as a diagnostic tool, as discussed in the context of the 2019 ESC guidelines 1. Therefore, a negative D-dimer can help exclude PE in low-risk patients, but an elevated level, even with a negative PE evaluation, necessitates a thorough investigation to determine the cause and appropriate management.
From the Research
Elevated D-Dimer with Negative Pulmonary Embolism
- A high D-dimer level can indicate the presence of a blood clot, but it is not specific to pulmonary embolism (PE) 2.
- A study found that among patients with markedly elevated D-dimer who did not have PE, the likely causes of their high D-dimer were infection, cardiovascular disease, surgery or trauma, new or active cancer, and miscellaneous causes 2.
- The study also found that patients with new or active cancer had poorer outcomes compared to those with no known cancer 2.
- Another study found that rivaroxaban administered before measuring D-dimer may reduce the sensitivity and increase false negative results of the test 3.
- The diagnostic work-up of suspected deep vein thrombosis or PE includes the sequential application of a clinical decision rule and D-dimer testing, and imaging and anticoagulation can be safely withheld in patients who are unlikely to have venous thromboembolism and have a normal D-dimer 4.
- The use of the D-dimer for detecting PE in the emergency department has been evaluated, and it was found that the D-dimer has a sensitivity of 95.7% and a specificity of 40.0% for the radiographic detection of PE 5.
- Age adjustment of the D-dimer threshold may help avoid unnecessary imaging in patients older than 50 years with an elevated D-dimer 5.
Possible Causes of Elevated D-Dimer
- Infection 2
- Cardiovascular disease, including aortic dissection 2
- Surgery or trauma 2
- New or active cancer 2
- Miscellaneous causes, such as recent surgery, medications, and chronic obstructive pulmonary disease 2, 5
Clinical Implications
- A negative PE diagnosis with an elevated D-dimer requires further evaluation to determine the cause of the elevated D-dimer 2.
- The use of rivaroxaban before measuring D-dimer may affect the diagnostic performance of the test 3.
- Age adjustment of the D-dimer threshold may help improve the diagnostic accuracy of the test 5.