Can a patient have Pulmonary Embolism (PE) with a negative D-Dimer (Deep Vein Thrombosis test)?

From the Guidelines

Yes, it is possible to have a pulmonary embolism (PE) with a negative D-dimer test, although this is uncommon. D-dimer tests have a high sensitivity (around 95%) but not perfect, meaning they can occasionally miss cases of PE. This is more likely to happen in patients with small, subsegmental PEs or when the test is performed several days after symptom onset as D-dimer levels may normalize over time. Certain patient populations, such as those on anticoagulation therapy prior to testing, may also have false-negative results. For this reason, clinical assessment remains crucial in diagnosing PE. If a patient has a high clinical probability of PE based on symptoms (shortness of breath, chest pain, rapid heart rate), risk factors (recent surgery, immobility, cancer), and physical examination findings, further imaging such as CT pulmonary angiography should be considered even with a negative D-dimer, as recommended by the American College of Physicians 1.

Key Considerations

• D-dimer tests are not foolproof and can miss cases of PE, especially in certain patient populations or when performed at a later stage after symptom onset.
• Clinical assessment is critical in diagnosing PE, and a high clinical probability of PE warrants further investigation, even with a negative D-dimer test.
• The use of age-adjusted D-dimer thresholds can help in determining the need for imaging in patients over 50 years old, as suggested by the American College of Physicians 1.
• CT pulmonary angiography is the preferred imaging modality for patients with a high pretest probability of PE, according to guidelines from the European Heart Journal 1 and the American College of Radiology 1.

Recommendations

• Do not rely solely on D-dimer to rule out PE when clinical suspicion is high, as missing this diagnosis can have serious consequences.
• Consider further imaging, such as CT pulmonary angiography, in patients with a high clinical probability of PE, even with a negative D-dimer test.
• Use clinical decision tools and validated clinical prediction rules to estimate pretest probability in patients with suspected acute PE, as advised by the American College of Physicians 1.

From the Research

Pulmonary Embolism with Negative D-Dimer

• Pulmonary embolism (PE) is a potentially life-threatening condition that requires urgent diagnosis and treatment 2.
• The symptoms of PE may be non-specific, and diagnosis relies on a clinical assessment and objective diagnostic testing 2.
• A clinical decision rule can determine the pre-test probability of PE, and if PE is "unlikely", a D-dimer test can be used to rule out the condition 2.
• If the D-dimer result is normal, PE can be excluded, but a negative D-dimer does not completely rule out PE, especially in patients with a high clinical probability of PE 3, 4.
• Studies have shown that a combination of a low clinical pre-test probability and a negative D-dimer can safely exclude PE without the need for further imaging 4, 5.
• However, in patients with a high probability of PE, a negative D-dimer does not exclude the diagnosis, and further imaging such as chest imaging is necessary 3.

Diagnostic Approach

• The diagnostic approach to PE involves a clinical assessment, D-dimer testing, and imaging studies such as computed tomography pulmonary angiogram (CTPA) or ventilation-perfusion (VQ) scan 2, 6.
• A negative CTPA can safely exclude PE, and a negative D-dimer assay can also exclude CTPA-detectable PE in patients with a low pretest clinical probability 5.
• The use of age-adjusted D-dimer cutoffs and multimodality ultrasound and V/Q single-photon emission computed tomography (SPECT) imaging are emerging diagnostic approaches for PE 6.

Clinical Implications

• A negative D-dimer does not completely rule out PE, and clinical judgment is necessary to determine the need for further testing 3, 4.
• The use of a clinical decision rule and D-dimer testing can risk stratify patients and allow for judicious use of diagnostic imaging 6.
• The diagnosis and management of PE require a multidisciplinary approach, and the use of direct oral anticoagulants has expanded the anticoagulation options for PE 2.