Laboratory Testing for Suspected Pulmonary Embolism
Initial Risk Stratification Determines Laboratory Testing Strategy
Begin with validated clinical prediction rules (Wells score, Geneva score, or PERC criteria) to stratify pretest probability—this determines whether any labs are needed at all. 1, 2
The laboratory workup is not a one-size-fits-all approach but rather depends entirely on your clinical probability assessment:
Low Pretest Probability Patients
If all 8 PERC criteria are met (age <50, HR <100, O₂ sat ≥95%, no unilateral leg swelling, no hemoptysis, no recent trauma/surgery, no prior VTE, no hormone use), order NO laboratory tests whatsoever—PE is safely excluded. 1, 2, 3
If PERC criteria are NOT all met, proceed to high-sensitivity D-dimer testing. 1, 2
Intermediate Pretest Probability Patients
Order high-sensitivity D-dimer as the initial and only laboratory test. 1, 2
Do not proceed directly to imaging without D-dimer assessment in this population. 1
High Pretest Probability Patients
Order NO laboratory tests—proceed directly to CT pulmonary angiography (CTPA). 1, 2, 3
D-dimer testing in high-risk patients wastes time and resources, as a negative result does not safely exclude PE in this population. 1, 3
D-Dimer Interpretation: Age-Adjusted Thresholds Are Critical
The interpretation of D-dimer results must account for patient age to avoid unnecessary imaging:
For Patients ≤50 Years Old
If D-dimer is below this threshold, PE is safely excluded without imaging (negative predictive value 99.5%). 3
For Patients >50 Years Old
Use age-adjusted D-dimer threshold: age × 10 ng/mL (e.g., 700 ng/mL for a 70-year-old). 1, 2, 3
This approach maintains sensitivity >97% while dramatically improving specificity, which otherwise drops to only 10% in patients >80 years using the standard 500 ng/mL cutoff. 2, 3
Age-adjusted thresholds increase the proportion of older patients in whom PE can be excluded from 6.4% to 30% without missing cases. 3
When D-Dimer is Elevated
If D-dimer exceeds the appropriate threshold (standard or age-adjusted), proceed immediately to CTPA. 3
Very high D-dimer levels (≥2,000-2,152 ng/mL) significantly increase positive predictive value for PE and may warrant hospital admission consideration. 3, 4
Essential Baseline Laboratory Tests
Beyond D-dimer, obtain these tests in all patients with suspected PE to assess severity and guide management:
Arterial blood gas to evaluate for hypoxemia. 3
Electrocardiogram to assess for right heart strain patterns. 3
The combination of tachypnea, pleuritic pain, and arterial hypoxemia is highly suggestive of PE, while absence of all three effectively excludes it. 3
Assay Type Matters
Only use high-sensitivity D-dimer assays (ELISA or turbidimetric methods) for ruling out PE in low and intermediate probability patients—these have 97% sensitivity. 3
Point-of-care D-dimer assays have lower sensitivity (88% vs. 95%) and should be avoided when laboratory-based tests are available. 3
Critical Pitfalls to Avoid
Don't Apply PERC to Patients >50 Years
Age <50 is one of the eight required PERC criteria, so PERC cannot be used in older patients. 3
For patients >50 years with low pretest probability, use age-adjusted D-dimer instead. 3
Don't Use Standard D-Dimer Cutoffs in Older Patients
Using the fixed 500 ng/mL threshold in patients >50 years leads to unnecessary imaging due to poor specificity. 1, 3
This is the most common error in PE workup and results in excessive radiation exposure and contrast-related complications. 2
Don't Order D-Dimer in High Pretest Probability Patients
- This delays definitive diagnosis and wastes resources, as these patients need imaging regardless of D-dimer results. 1, 2, 3
Don't Ignore Clinical Context When D-Dimer is Elevated
D-dimer elevation alone is not diagnostic of PE—it has high negative predictive value but poor positive predictive value. 2
Proceeding to CTPA with elevated D-dimer but low clinical suspicion leads to overdiagnosis of clinically insignificant emboli. 2
Special Populations
Hospitalized Inpatients
D-dimer specificity is lower in inpatients due to comorbidities (inflammation, infection, malignancy), but testing remains appropriate as sensitivity stays high. 3, 5
Only 10.6% of inpatients with nondiagnostic imaging had negative D-dimer results, compared to 31.8% of outpatients. 5
Patients with Prior VTE
The standard diagnostic algorithm is safe but less efficient in patients with previous VTE, as only 15% can be excluded without CTPA (versus much higher rates in patients without prior VTE). 6
Consider lower-extremity venous ultrasonography, as finding proximal DVT is sufficient to warrant anticoagulation without further PE imaging. 3
Patients with Malignancy
- D-dimer cutoff points are higher in cancer patients—consider a threshold of 2,652 ng/mL in patients >65 years with active malignancy. 4