What blood tests are used to diagnose unprovoked Pulmonary Embolism (PE)?

Blood Tests for Unprovoked Pulmonary Embolism

D-dimer is the primary blood test used in the diagnostic workup of unprovoked PE, but it should only be ordered in patients with low or intermediate clinical probability—not as a screening test in all suspected cases. 1

D-Dimer Testing Strategy

When to Order D-Dimer:

• D-dimer measurement is recommended as the initial diagnostic test in patients with low or intermediate pretest probability of PE who do not meet all Pulmonary Embolism Rule-Out Criteria (PERC). 1
• The American College of Physicians explicitly recommends against using imaging studies as the initial test in low or intermediate probability patients—D-dimer should come first. 1
• In patients with high clinical probability (>40%), proceed directly to CT imaging without D-dimer testing, as it will not change management. 2

D-Dimer Interpretation:

• A negative D-dimer result below 500 ng/mL (in patients under 50 years) effectively rules out PE without need for CT imaging, with a post-test probability less than 1.85%. 1, 2
• Age-adjusted D-dimer thresholds can be used in patients 50 years and older for improved specificity. 2
• The YEARS model allows for adapted D-dimer cutoffs: PE is excluded with D-dimer <1000 ng/L in patients without clinical items (signs of DVT, hemoptysis, or PE as most likely diagnosis), or <500 ng/L in patients with one or more clinical items. 3

Critical Limitations of D-Dimer

When D-Dimer is NOT Useful:

• D-dimer has severely limited utility in hospitalized patients due to high prevalence of conditions causing elevated levels (infection, cancer, inflammation, recent surgery), allowing PE to be ruled out in less than 10% of cases. 3, 4
• The most common diagnostic error is ordering CT angiography without first obtaining D-dimer in low-to-intermediate risk patients, leading to unnecessary radiation exposure, contrast nephropathy, and overdiagnosis of clinically insignificant PE. 1

Additional Blood Tests

Cardiac Biomarkers (for Risk Stratification, Not Diagnosis):

• Troponin and BNP/NT-proBNP are used for prognostic assessment and risk stratification in confirmed PE, particularly to identify right ventricular dysfunction, but are not diagnostic tests for PE itself. 3
• Elevated creatinine kinase MB isoenzyme may indicate RV ischemia in massive PE but is not part of the standard diagnostic algorithm. 3

Diagnostic Algorithm Summary

1. First: Assess clinical probability using validated scores (Wells, Geneva) or clinical gestalt 3, 4, 2
2. Low/Intermediate Probability: Order D-dimer
   • If negative (<500 ng/mL): PE excluded, no imaging needed 1, 2
   • If positive: Proceed to CT pulmonary angiography 4
3. High Probability: Skip D-dimer, proceed directly to CT imaging 2
4. Hemodynamically Unstable: Echocardiography at bedside, not blood tests 3, 4

Common Pitfall: Using D-dimer in hospitalized patients or those with high clinical probability where it has minimal utility and will likely be falsely elevated. 3, 4