What is the role of D-dimer (D-dimer test) in diagnosing and managing pulmonary embolism?

D-Dimer in Pulmonary Embolism

Primary Diagnostic Role: Rule-Out Test in Low-Risk Patients

D-dimer is a highly sensitive rule-out test for pulmonary embolism that should be used in combination with clinical probability assessment—a negative highly sensitive D-dimer (ELISA or equivalent) in patients with low or intermediate pretest probability safely excludes PE without further imaging. 1

The fundamental principle is that D-dimer has excellent sensitivity (96-99%) but poor specificity (35-51%), making it ideal for exclusion but useless for confirmation of PE. 1

Clinical Decision Algorithm

Step 1: Assess Pretest Probability First

Use validated clinical decision rules (Wells score or revised Geneva score) to categorize patients into low, intermediate, or high probability categories before ordering D-dimer. 1

Key point: Never order D-dimer in high clinical probability patients—proceed directly to CT pulmonary angiography, as the negative predictive value is too low in this population. 1

Step 2: Apply D-Dimer Based on Risk Stratification

Low pretest probability patients:

• Order highly sensitive D-dimer (ELISA or turbidimetric assay) 1
• If D-dimer <500 ng/mL: PE excluded, no further testing needed, 3-month thromboembolic risk <1% 1, 2
• If D-dimer ≥500 ng/mL: Proceed to CT pulmonary angiography 1

Intermediate pretest probability patients:

• D-dimer can be used, though evidence is less robust than for low-risk patients 1
• Negative D-dimer excludes PE (Level C recommendation) 1
• Positive D-dimer requires CT pulmonary angiography 1

High pretest probability patients:

• Skip D-dimer entirely and proceed directly to imaging 1
• D-dimer adds no value and delays diagnosis 1

Age-Adjusted D-Dimer Cutoffs: Critical for Elderly Patients

For patients >50 years old, use age-adjusted cutoffs (age × 10 ng/mL) to improve specificity while maintaining >97% sensitivity. 1

This approach increases the proportion of elderly patients in whom PE can be safely excluded from 6.4% to 30% without additional false-negative findings. 1 Standard D-dimer specificity drops to only 10% in patients >80 years old, making age-adjusted cutoffs essential in this population. 1

Alternative Strategy: YEARS Algorithm

The YEARS clinical decision rule uses modified D-dimer cutoffs based on clinical presentation: 1

• No clinical items present (no signs of DVT, no hemoptysis, PE not most likely diagnosis): PE excluded if D-dimer <1000 ng/mL 1
• One or more clinical items present: PE excluded if D-dimer <500 ng/mL 1
• All other patients require CT pulmonary angiography 1

Assay Selection Matters

Only highly sensitive quantitative D-dimer assays (ELISA or turbidimetric) should be used for PE exclusion. 1

• Classical ELISA: Sensitivity 98%, validated in outcome studies 1
• Rapid ELISA: Sensitivity 100%, validated in outcome studies 1
• Point-of-care assays: Lower sensitivity (88% vs 95%), should only be used in low pretest probability patients 1
• Qualitative latex tests: Inadequate sensitivity (87-92%), should NOT be used to rule out PE 1

Populations Where D-Dimer Has Limited Utility

D-dimer testing is less useful or requires modified interpretation in: 1

• Hospitalized patients: Number needed to test increases from 3 to >10 to exclude one PE 1
• Cancer patients: Specificity drops to 18-21% 1
• Pregnant patients: D-dimer increases progressively, particularly beyond first trimester 1
• Elderly patients: Requires age-adjusted cutoffs 1
• Post-surgical patients: High false-positive rate 1

Critical Pitfalls to Avoid

1. Never use positive D-dimer alone to diagnose PE—confirmation with imaging is mandatory, as specificity is only 35-51%. 1

2. Never skip clinical probability assessment—D-dimer without pretest probability stratification leads to excessive false-positives and unnecessary imaging. 1, 2

3. Never use D-dimer in isolation—the SimpliRED study explicitly demonstrated that D-dimer should not be used alone to exclude PE. 3

4. Don't order D-dimer indiscriminately—if ordered on patients with very low or no risk for PE, false-positives increase harms from unnecessary CT scans. 1

Markedly Elevated D-Dimer Levels

When D-dimer is extremely elevated (>2000-5000 ng/mL), this carries different implications: 4

• D-dimer >2152 ng/mL has 53% positive predictive value for PE in selected populations 5
• D-dimer 3-4× upper limit of normal warrants hospital admission consideration even without severe symptoms due to increased mortality risk 4
• Consider alternative diagnoses: aortic dissection (D-dimer >500 ng/mL has 94-100% sensitivity), malignancy (29% prevalence with D-dimer >5000 ng/mL), or sepsis 4

Integration with Imaging

When D-dimer is positive or clinical probability is high, multidetector CT pulmonary angiography is the imaging test of choice. 1

• Negative CTPA alone can exclude PE in low/intermediate probability patients (Level B recommendation) 1
• For high pretest probability patients with negative CTPA, consider additional testing (lower extremity ultrasound, V/Q scan) before excluding PE 1
• Compression ultrasonography shows DVT in 30-50% of patients with PE, and finding proximal DVT is sufficient to warrant anticoagulation without further testing 1

Outcome Data Supporting D-Dimer Strategy

The negative predictive value of combining low clinical probability with negative D-dimer is 99-99.5%, with 3-month thromboembolic risk of 0.6-1.0% when anticoagulation is withheld. 2, 6 This safety profile supports the widespread use of D-dimer as a rule-out test in appropriately selected patients. 1, 2