From the Guidelines
For patients with suspected pulmonary embolism and a negative D-dimer test, pulmonary embolism can generally be safely excluded without further testing if the patient has a low or intermediate clinical probability of PE, as stated in the 2022 update of the ACR Appropriateness Criteria for suspected pulmonary embolism 1. This approach is based on the high negative predictive value of D-dimer in these patients, which is greater than 99%, making it a reliable "rule-out" test. However, clinical judgment remains crucial, and if clinical suspicion persists despite the negative D-dimer, or if the patient has a high pre-test probability of PE, additional imaging such as CT pulmonary angiography should be considered. Some key points to consider in managing these patients include:
- The limitations of D-dimer, which, while highly sensitive, lacks specificity and can occasionally produce false negatives, particularly in patients with small subsegmental emboli, those who have had symptoms for more than a week, or patients on anticoagulation therapy 1.
- The importance of clinical probability assessment, as guided by decision tools such as the Wells criteria, in determining the need for further testing.
- The role of CT pulmonary angiography as a second-line test in patients with an elevated D-dimer level or a high clinical probability of PE.
- The need to pursue alternative diagnoses to explain the patient's symptoms when PE is excluded, and to provide close follow-up with instructions to return if symptoms worsen or new concerning symptoms develop. Overall, this approach balances the need to avoid missing a potentially fatal diagnosis with the need to prevent unnecessary radiation exposure and contrast administration from CT imaging, prioritizing morbidity, mortality, and quality of life as outcomes.
From the Research
Pulmonary Embolism with Negative D-Dimer
- A negative D-dimer test can help rule out pulmonary embolism (PE) in patients with a low pre-test probability 2, 3, 4, 5, 6.
- Studies have shown that patients with a low clinical probability of PE and a negative D-dimer result have a low risk of venous thromboembolism (VTE) during follow-up 3, 4, 5.
- The combination of a negative D-dimer result and a non-high pre-test probability can effectively and safely exclude PE in outpatients with suspected PE 4.
- A negative D-dimer test is valuable in ruling out PE in patients who present to the emergency setting with a low pre-test probability, but may have less utility in older populations 5.
- A retrospective study found that a negative CT pulmonary angiogram (CTPA) and a negative D-dimer assay can safely exclude CTPA-detectable PE in patients with a low pre-test clinical probability 6.
Management of Patients with Suspected Pulmonary Embolism and Negative D-Dimer
- Patients with a low pre-test probability of PE and a negative D-dimer result can be considered for alternative diagnoses and do not require further diagnostic testing for PE 2, 3, 4.
- In patients with a moderate or high pre-test probability of PE, further diagnostic testing such as CTPA or ventilation-perfusion scintigraphy may be necessary even with a negative D-dimer result 2, 3, 5.
- The use of clinical prediction rules such as the Wells or Geneva scores can help determine the pre-test probability of PE and guide further management 2, 3, 4, 5.