Can a pulmonary embolism (PE) occur with a low D-dimer (D-dimer)

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From the Guidelines

Yes, it is possible to have a pulmonary embolism (PE) with a low D-dimer level, although this is uncommon. D-dimer is a blood test that measures a protein fragment produced when a blood clot dissolves in the body. While a negative or low D-dimer test has a high negative predictive value (meaning it's good at ruling out PE in low-risk patients), it is not 100% accurate. Certain factors can lead to false-negative results, including small clots, clots that have been present for more than a week, anticoagulant therapy prior to testing, or certain technical limitations of the test itself 1. This is why clinical assessment tools like the Wells score or PERC rule are used alongside D-dimer testing. If a patient has high clinical suspicion for PE based on symptoms (shortness of breath, chest pain, rapid heart rate) and risk factors (immobility, recent surgery, cancer, pregnancy), further imaging such as CT pulmonary angiography should be considered even with a negative D-dimer 1. Never dismiss concerning symptoms solely based on a negative D-dimer result.

Key Points to Consider

  • A low D-dimer level does not completely rule out the possibility of a pulmonary embolism, especially in patients with high clinical suspicion or risk factors.
  • Clinical assessment tools, such as the Wells score or PERC rule, should be used in conjunction with D-dimer testing to evaluate patients with suspected PE.
  • Further imaging, such as CT pulmonary angiography, may be necessary even with a negative D-dimer result if clinical suspicion remains high.
  • The American College of Physicians recommends using validated clinical prediction rules to estimate pretest probability in patients with suspected acute PE, and reserving imaging studies for patients with high pretest probability or those with intermediate pretest probability and a positive D-dimer result 1.

Recommendations for Practice

  • Use clinical judgment and assessment tools to evaluate patients with suspected PE, rather than relying solely on D-dimer results.
  • Consider further imaging in patients with high clinical suspicion or risk factors, even with a negative D-dimer result.
  • Follow guidelines and recommendations from professional societies, such as the American College of Physicians, for the evaluation and management of patients with suspected PE.

From the Research

Pulmonary Embolism with Low D-Dimer

  • A pulmonary embolism (PE) can occur with a low D-dimer level, although it is rare 2, 3, 4, 5, 6.
  • The D-dimer test is highly sensitive for PE, but not specific, meaning that a low D-dimer level can help rule out PE, but a high level does not necessarily confirm it 2.
  • Studies have shown that a D-dimer level below a certain threshold (e.g. 500 micrograms/L) can be used to exclude PE in outpatients with suspected PE, with a negative predictive value of 99% or higher 2, 5.
  • However, using a lower D-dimer threshold (e.g. 1000 ng per milliliter) in patients with low clinical pretest probability can also safely exclude PE, with a negative predictive value of 100% 5.
  • It is essential to consider the clinical pretest probability and other diagnostic criteria, such as the Wells score, when interpreting D-dimer results 3, 4, 5.
  • In some cases, a low D-dimer level may not completely rule out PE, and further diagnostic testing, such as computed tomography pulmonary angiography (CTPA), may be necessary 3, 4, 6.

Diagnostic Thresholds

  • Different studies have used various D-dimer thresholds to exclude PE, including:
    • 500 micrograms/L 2
    • 1000 ng per milliliter 5
    • 0.4 microg/mL 6
    • 0.5 microg/mL 4
  • The choice of threshold depends on the clinical context, including the patient's pretest probability and other diagnostic criteria 3, 4, 5.

Clinical Implications

  • A low D-dimer level can help reduce the need for further diagnostic testing, such as CTPA, in patients with suspected PE 5, 6.
  • However, it is crucial to consider the clinical pretest probability and other diagnostic criteria to avoid missing cases of PE 3, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

D-dimer testing for suspected pulmonary embolism in outpatients.

American journal of respiratory and critical care medicine, 1997

Research

Retrospective validation of the pulmonary embolism rule-out criteria rule in 'PE unlikely' patients with suspected pulmonary embolism.

European journal of emergency medicine : official journal of the European Society for Emergency Medicine, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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