D-Dimer Testing in Suspected Pulmonary Embolism
Direct Answer
In adults with suspected PE and low or intermediate pre-test probability, use a high-sensitivity quantitative D-dimer with age-adjusted cutoffs (age × 10 ng/mL for patients >50 years) to safely rule out PE without imaging; if the D-dimer is positive, proceed immediately to CT pulmonary angiography. 1
Clinical Probability Assessment Must Come First
Before ordering any D-dimer test, you must stratify patients using validated prediction rules—either the Wells score or revised Geneva score. 1 This step is non-negotiable because the post-test probability depends critically on pre-test probability. 1
Key clinical features to assess include: 1
- Signs of deep vein thrombosis (unilateral leg swelling)
- Hemoptysis
- Recent surgery or trauma (within 4 weeks)
- Prior history of venous thromboembolism
- Active malignancy
- Heart rate >100 beats per minute
- Immobilization ≥3 days
- Whether PE is the most likely diagnosis
When to Order D-Dimer (and When Not To)
Low Pre-Test Probability Patients
- First apply PERC criteria (age <50, HR <100, O₂ sat ≥95%, no leg swelling, no hemoptysis, no recent trauma/surgery, no prior VTE, no hormone use). 1
- If all 8 PERC criteria are met, stop—no D-dimer or imaging needed. 1, 2
- If PERC is not met, order high-sensitivity D-dimer. 1, 2
Intermediate Pre-Test Probability Patients
High Pre-Test Probability Patients
- Do NOT order D-dimer—proceed directly to CT pulmonary angiography. 1, 2 The negative predictive value of D-dimer is insufficient in this population (even with highly sensitive assays), and testing only wastes time. 1 Recent data suggest D-dimer may be safe in high-probability patients, but the confidence interval was too wide to change practice guidelines. 3
D-Dimer Interpretation: Age-Adjusted Cutoffs Are Critical
Standard Cutoff (Patients ≤50 Years)
Age-Adjusted Cutoff (Patients >50 Years)
- Use age × 10 ng/mL as the threshold (e.g., 70 years old = 700 ng/mL cutoff). 1, 2
- This is essential because D-dimer specificity drops to only 10% in patients >80 years using the standard 500 ng/mL cutoff. 1, 2
- Age-adjusted cutoffs maintain sensitivity >97% while dramatically improving specificity—increasing the proportion of elderly patients in whom PE can be excluded from 6.4% to 30% without missing cases. 1, 2
Specificity improvements by age group: 2
- Ages 51-60: 57.6% → 62.3%
- Ages 61-70: 39.4% → 49.5%
- Ages 71-80: 24.5% → 44.2%
- Ages >80: 14.7% → 35.2%
What to Do Based on D-Dimer Results
Negative D-Dimer (Below Appropriate Threshold)
- PE is ruled out—no imaging needed. 1, 2
- The three-month thromboembolic risk is <1% in patients left untreated based on negative D-dimer combined with low or intermediate clinical probability. 1, 4
- The negative predictive value is 99.5% when combined with appropriate pre-test probability assessment. 2
Positive D-Dimer (Above Threshold)
- Proceed immediately to CT pulmonary angiography. 1, 2
- Remember that D-dimer has high negative predictive value but poor positive predictive value—many conditions elevate D-dimer (cancer, hospitalization, infection, pregnancy, advanced age). 1, 2
Assay Requirements Matter
Only use high-sensitivity quantitative D-dimer assays (ELISA or turbidimetric methods) with sensitivity ≥95%. 1
Avoid point-of-care D-dimer assays when laboratory-based tests are available—they have lower sensitivity (88% vs. 95%) and should only be used in low pre-test probability patients if necessary. 1, 2
Moderately sensitive assays (latex-derived, whole-blood agglutination) are safe only in PE-unlikely or low clinical probability patients, not in intermediate probability. 1
Special Populations and Pitfalls
Hospitalized Patients
- D-dimer specificity is lower in inpatients due to comorbidities and inflammation, but sensitivity remains high, so testing is still appropriate. 1, 2
- The number needed to test rises from 3 in the general emergency department population to >10 in hospitalized patients. 1
Patients with Cancer
- D-dimer is frequently elevated, reducing specificity. 1 However, a negative D-dimer still safely excludes PE when combined with low or intermediate clinical probability. 1
Pregnant Patients
- D-dimer specificity is reduced during pregnancy. 1 Consider lower-extremity venous ultrasonography before CT in first trimester to reduce radiation exposure. 2
Markedly Elevated D-Dimer (≥5,000 ng/mL)
- In hospitalized patients with pneumonia and D-dimer ≈10× upper limit of normal, proceed directly to CTPA without calculating probability scores—this degree of elevation has high positive predictive value and is associated with increased mortality. 2
Common Pitfalls to Avoid
Never use the standard 500 ng/mL cutoff in patients >50 years—this leads to massive overuse of imaging due to poor specificity. 1, 2
Never order D-dimer in high pre-test probability patients—it wastes resources and delays definitive diagnosis. 1, 2
Never order D-dimer before completing clinical probability assessment—this leads to misinterpretation and unnecessary imaging. 2
Never apply PERC to patients >50 years—age <50 is one of the eight required PERC criteria. 2
Never use point-of-care assays when laboratory-based tests are available—the lower sensitivity (88%) increases false negatives. 1, 2
Never order CTPA as the first test in low or intermediate probability patients—D-dimer can safely exclude PE in 30-50% of such cases. 2
Diagnostic Algorithm Summary
Step 1: Assess clinical probability using Wells or Geneva score 1
Step 2: Apply decision pathway based on probability:
- Low probability + all PERC met → Stop, no further testing 1, 2
- Low probability + PERC not met → Order D-dimer 1, 2
- Intermediate probability → Order D-dimer 1, 2
- High probability → Skip D-dimer, go directly to CTPA 1, 2
Step 3: Interpret D-dimer using appropriate cutoff:
Step 4: Act on result: