How do I rule out a pulmonary embolism (PE) diagnosis in a patient presenting with shortness of breath and tachycardia?

Ruling Out Pulmonary Embolism: A Structured Diagnostic Approach

To safely eliminate a PE diagnosis, you must first stratify pretest probability using a validated clinical prediction rule (Wells or revised Geneva score), then apply either PERC criteria (for low-risk patients under 50) or D-dimer testing with age-adjusted cutoffs (for patients over 50 or those who are PERC-positive), avoiding imaging entirely when these criteria safely exclude PE. 1

Step 1: Calculate Pretest Probability

Use either the Wells score or revised Geneva score to categorize your patient 1:

Revised Geneva Score Components 1:

• Previous PE or DVT: 3 points (original) / 1 point (simplified)
• Heart rate 75-94 bpm: 3 points / 1 point
• Heart rate ≥95 bpm: 5 points / 2 points
• Surgery or fracture within past month: 2 points / 1 point
• Hemoptysis: 2 points / 1 point
• Active cancer: 2 points / 1 point
• Unilateral lower-limb pain: 3 points / 1 point
• Pain on deep venous palpation and unilateral edema: 4 points / 1 point
• Age >65 years: 1 point / 1 point

Risk Stratification 1:

• Low probability: 0-3 points (original) or 0-1 (simplified) — ~10% PE prevalence
• Intermediate probability: 4-10 points (original) or 2-4 (simplified) — ~30% PE prevalence
• High probability: ≥11 points (original) or ≥5 (simplified) — ~65% PE prevalence

Two-level classification:

• PE-unlikely: 0-5 points (original) or 0-2 (simplified) — ~12% PE prevalence
• PE-likely: ≥6 points (original) or ≥3 (simplified) — ~30% PE prevalence

Step 2: Apply PERC Rule (Low Pretest Probability Patients Only)

If your patient has LOW pretest probability, apply the 8 PERC criteria 1:

All 8 Criteria Must Be Met 1:

1. Age <50 years
2. Heart rate <100 beats per minute
3. Oxygen saturation >94% (at sea level)
4. No unilateral leg swelling
5. No hemoptysis
6. No recent trauma or surgery
7. No history of VTE (prior PE or DVT)
8. No hormone use (oral contraceptives or hormone replacement)

If ALL 8 PERC criteria are met: PE is ruled out. Stop here. No D-dimer, no imaging. 1, 2

Critical Caveat About PERC:

PERC should ONLY be applied to patients with LOW pretest probability 1. The sensitivity is 96-97% with a negative likelihood ratio of 0.15, yielding a false-negative rate of approximately 1.4% 1. However, some studies in populations with higher PE prevalence have shown PERC may miss up to 6-8% of cases 3, 4, so never apply PERC to intermediate or high-risk patients 1.

Step 3: D-Dimer Testing Strategy

For Low or Intermediate Pretest Probability Patients Who Are PERC-Positive:

Use high-sensitivity D-dimer (ELISA or ELISA-derived assays with ≥95% sensitivity) 1:

Age-Specific Cutoffs 1, 5:

• Patients ≤50 years: Use standard cutoff of <500 ng/mL
• Patients >50 years: Use age-adjusted cutoff = age × 10 ng/mL

The age-adjusted approach is critical because standard D-dimer specificity drops to only 10% in patients over 80 years old 1. Using age-adjusted cutoffs increases the number of patients in whom PE can be excluded from 6.4% to 30% without additional false-negative findings 1, 5.

Specificity Improvements with Age-Adjusted D-Dimer 5:

• Ages 51-60: specificity increases from 57.6% to 62.3%
• Ages 61-70: specificity increases from 39.4% to 49.5%
• Ages 71-80: specificity increases from 24.5% to 44.2%
• Ages >80: specificity increases from 14.7% to 35.2%

If D-dimer is below the appropriate threshold: PE is ruled out. Stop here. No imaging needed. 1 The negative predictive value is 99.5% when combined with low clinical probability 1.

If D-dimer is elevated above the threshold: Proceed to CT pulmonary angiography (CTPA). 1, 2

For High Pretest Probability Patients:

Do NOT order D-dimer. Proceed directly to CTPA. 1 A negative D-dimer does not safely exclude PE in high-risk patients, even with highly sensitive assays 1.

Step 4: When Imaging Cannot Be Avoided

If D-dimer is elevated or pretest probability is high, order CTPA as first-line imaging 1, 6:

Alternative Imaging Options 6:

• Ventilation-perfusion (V/Q) scan: Reserve for patients with contraindications to CTPA (renal insufficiency, contrast allergy) or when CTPA is unavailable
• Lower extremity venous ultrasound: Consider in patients with obvious DVT signs, pregnancy, or as adjunct when CTPA is negative but suspicion remains high

Common Pitfalls to Avoid

Critical Errors 1, 5, 2:

1. Never apply PERC to patients over 50 years old — age <50 is one of the eight required criteria 1, 5

2. Never use standard 500 ng/mL D-dimer cutoff in patients over 50 — this leads to unnecessary imaging due to poor specificity 1, 5

3. Never order D-dimer in high pretest probability patients — it wastes time and resources; proceed directly to imaging 1

4. Never apply PERC to intermediate or high-risk patients — this may lead to missed diagnoses 1

5. Never use point-of-care D-dimer assays when laboratory-based tests are available — they have lower sensitivity (88% vs. 95%) 5

Special Population Considerations

Hospitalized Patients 5:

D-dimer specificity is lower in inpatients due to comorbidities (cancer, infection, inflammatory disease), but testing remains appropriate as sensitivity stays high. The number needed to test rises from 3 in the general ED population to ≥10 in hospitalized patients 1.

Pregnant Patients 1:

D-dimer is frequently elevated during pregnancy. Consider lower-extremity venous ultrasonography before CT in first trimester to reduce radiation exposure 5.

Cancer Patients 1:

D-dimer is more frequently elevated in patients with active malignancy, reducing specificity but maintaining high sensitivity for ruling out PE when negative.