When should d-dimer results be waited for before proceeding with advanced imaging in patients with suspected pulmonary embolism (PE), versus proceeding directly to computed tomography (CT) pulmonary angiography in high-risk patients?

Diagnostic Approach to Suspected Pulmonary Embolism: D-dimer vs. Direct Advanced Imaging

For patients with suspected PE, D-dimer testing should be performed first in low and intermediate risk patients, while high-risk patients should proceed directly to CT pulmonary angiography without waiting for D-dimer results.

Risk Stratification and Initial Assessment

The diagnostic approach to suspected pulmonary embolism should follow a structured algorithm based on clinical probability assessment:

1. Clinical Probability Assessment:

   • Use validated clinical prediction rules such as Wells criteria or Geneva score to categorize patients into low, intermediate, or high pretest probability 1
   • This assessment is critical for determining the subsequent diagnostic pathway

2. D-dimer Testing:

   • Low or Intermediate Probability Patients:

     • D-dimer measurement is recommended as the first step 1
     • A negative D-dimer result in low/intermediate risk patients safely excludes PE without need for imaging (negative predictive value >99%) 1, 2
     • Age-adjusted D-dimer thresholds (age × 10 ng/mL for patients >50 years) should be used to improve specificity 1

   • High Probability Patients:

     • D-dimer testing is not recommended in high clinical probability patients 1
     • Proceed directly to CTPA without waiting for D-dimer results 1
     • This is because a negative D-dimer result does not safely exclude PE in high-risk patients, even when using highly sensitive assays 1

When to Skip D-dimer and Go Directly to Advanced Imaging

Advanced imaging (primarily CTPA) should be performed directly without waiting for D-dimer results in:

1. High clinical probability patients 1

   • The negative predictive value of D-dimer in high-risk patients is insufficient to rule out PE

2. Patients with hemodynamic instability (high-risk PE) 1

   • Bedside echocardiography or emergency CTPA should be performed immediately
   • Intravenous anticoagulation should be initiated without delay

3. Hospitalized patients 1

   • D-dimer has limited utility in this population due to high false-positive rates
   • The number needed to test to obtain a clinically relevant negative result is high

Imaging Modalities for Suspected PE

1. CT Pulmonary Angiography (CTPA):

   • First-line imaging test for most patients with suspected PE 1
   • High diagnostic accuracy with sensitivity of 83% and specificity of 96% 3
   • Can visualize pulmonary arteries down to subsegmental level
   • May reveal alternative diagnoses in approximately 35% of patients without PE 3

2. Ventilation/Perfusion (V/Q) Scan:

   • Alternative for patients with contraindications to CTPA 1
   • Preferred for pregnant women and young female patients to reduce radiation exposure 1, 3
   • Normal perfusion scan safely excludes PE 1

Important Caveats and Pitfalls

1. Negative CTPA in High-Risk Patients:

   • A negative CTPA alone is not sufficient to exclude PE in high clinical probability patients 1
   • Additional testing (e.g., lower extremity ultrasound, V/Q scan) should be considered 1

2. Subsegmental PE on CTPA:

   • The clinical significance of isolated subsegmental PE remains uncertain 1, 3
   • Further testing may be considered to confirm diagnosis 1

3. D-dimer in Special Populations:

   • D-dimer has reduced specificity in elderly patients, pregnant women, and hospitalized patients 1
   • False-positive results are common in these populations, potentially leading to unnecessary imaging

4. Overuse of CTPA:

   • Studies show suboptimal use of clinical prediction rules before ordering CTPA 4
   • Following the structured algorithm reduces unnecessary radiation exposure and contrast administration

Conclusion

The diagnostic approach to suspected PE should be risk-stratified. For low and intermediate risk patients, D-dimer testing should be performed first to potentially avoid unnecessary imaging. For high-risk patients or those with hemodynamic instability, proceed directly to CTPA without waiting for D-dimer results to avoid delays in diagnosis and treatment of this potentially fatal condition.