Does a higher D-dimer (D-dimer) level correlate with a higher probability of pulmonary embolism (PE)?

From the Guidelines

Yes, a higher D-dimer level generally correlates with a higher probability of pulmonary embolism (PE), though the relationship is not perfectly linear. D-dimer is a fibrin degradation product that increases when blood clots are being actively broken down in the body. In patients with suspected PE, D-dimer testing is most valuable as a "rule-out" test due to its high sensitivity but limited specificity. A normal D-dimer level (typically <500 ng/mL, though age-adjusted cutoffs are often used for older patients) effectively excludes PE in patients with low to moderate clinical probability, as suggested by the American College of Physicians 1. However, as D-dimer levels increase above the threshold, the positive predictive value improves somewhat, meaning very elevated levels (such as >4000 ng/mL) are more concerning for PE than borderline elevations.

Key Considerations

• D-dimer can be elevated in many other conditions including infection, inflammation, cancer, pregnancy, and recent surgery, which limits its specificity 1.
• Clinical assessment tools like the Wells score or PERC rule should be used alongside D-dimer testing to improve diagnostic accuracy, as recommended by the American College of Physicians 1.
• Patients with high clinical suspicion or significantly elevated D-dimer levels should undergo imaging studies like CT pulmonary angiography for definitive diagnosis of PE, in line with guidelines from the European Heart Journal 1 and the American College of Physicians 1.

Diagnostic Approach

• For patients with low pretest probability of PE, the PERC criteria should be applied, and if all criteria are met, D-dimer testing is not necessary, as stated in the guidelines from the American College of Physicians 1.
• For patients with intermediate pretest probability of PE, D-dimer testing is warranted, and a normal D-dimer level can effectively rule out PE, while an elevated level should prompt imaging studies, as suggested by the American College of Physicians 1.
• For patients with high pretest probability of PE, imaging studies with CT pulmonary angiography should be performed directly, without the need for D-dimer testing, as recommended by the European Heart Journal 1 and the American College of Physicians 1.

From the Research

Correlation between D-dimer levels and Pulmonary Embolism (PE)

• A higher D-dimer level is associated with a higher probability of pulmonary embolism (PE) 2, 3, 4.
• The study by 2 found that patients with central embolisms in the pulmonary trunk or arteries had higher average D-dimer levels (7.1 mg/L) compared to those with no PE (3.6 mg/L) or peripheral PE (4.3 mg/L).
• Another study by 3 found that patients who died from PE had higher median D-dimer levels (4578 vs 2946 microg/l) than those who survived, and mortality increased with increasing D-dimer levels.
• The study by 4 found that patients with D-dimer levels higher than 2,152 ng/mL had a significantly increased risk of PE, with a positive predictive value (PPV) of 53% and a negative predictive value (NPV) of 82%.

Diagnostic Accuracy of D-dimer levels

• D-dimer levels can be used to exclude PE in low-risk patients, with a high negative predictive value (NPV) 5, 6.
• A study by 5 found that managing patients with suspected PE based on pretest probability and D-dimer result is safe and decreases the need for diagnostic imaging, with a negative predictive value of 99.5% for the combined strategy.
• Another study by 6 found that a plasma D-dimer concentration below 500 micrograms/L allows the exclusion of PE in 29% of outpatients suspected of having PE, with a negative predictive value of 99%.

Clinical Implications

• The use of D-dimer levels in combination with clinical probability and imaging results can improve diagnostic accuracy and efficiency for PE 2.
• Establishing reliable D-dimer cutoff values may help clinicians better stratify patient risk and make informed decisions about the need for imaging 2.
• Patients with higher D-dimer levels may require closer monitoring and more aggressive treatment, while those with lower levels may be at lower risk of PE 3, 4.