Bottom Line Up Top: A negative D-Dimer likely excludes significant pulmonary embolism (PE) in all patients but the low chance of getting a negative result makes a D-Dimer first approach of low clinical utility in the high pre-test probability group.
Clinical Scenario: A 45-year-old man with malignant melanoma presents with right-sided pleuritic chest pain for 3 days. Vitals are HR 97, BP 128/78, O2 sat 99% on RA, RR 16, Temp 98.8. The patient has a history of a provoked PE after a tib-fib fracture 15 years ago. He complains of left leg pain but there is no swelling present and the patient’s exam is otherwise unremarkable. The patient’s Revised Geneva Score = 13 (high risk > 10). Prior to your evaluation, a D-Dimer was ordered and resulted at 200 ng/ml (normal < 250 ng/ml). Despite the result, you contemplate whether you should obtain a CT pulmonary angiogram (CTPA) since the patient has a high pre-test probability for PE.
What Your Gut Says: Get the CTPA; high-risk patients cannot be adequately risk-stratified with a negative D-Dimer alone.
What The Evidence Says: European and American guidelines emphasize a sequential diagnostic approach based on pre-test probability assessment using either a formal clinical decision instrument (e.g., Wells’, Revised Geneva) or clinical gestalt. D-Dimer testing is commonly used to “rule out” PE in low- and moderate-risk patients due to its high sensitivity and negative predictive value. It’s important to note that no test or test strategy is perfect (they will all have some rate of false negatives and false positives) and that there is always residual risk for the disease in question regardless of the evaluation. In low- to moderate-risk patients for PE, a negative D-Dimer (either by absolute or age-adjusted threshold) lowers the risk to < 2%. This 2% mark is widely accepted as the threshold at which additional testing is more likely to harm the patient than offer benefit.
The current standard care for evaluating PE advises against D-Dimer testing in patients with a high pre-test clinical probability because a negative result doesn’t lower the probability below the 2% threshold; a CTPA would be required whether the D-Dimer was positive or negative. In this situation, obtaining a D-Dimer delays diagnostic testing without offering additional benefit. However, there is scant data looking at the true negative predictive value of a D-Dimer in the high pre-test probability group.
A recent publication in Academic Emergency Medicine attempts to shed light on this area. In the study, researchers performed a secondary analysis of data collected from three studies (PROPER, MODIGLIANI, and TRYSPEED). They found that out of 70 high pre-test probability patients with a negative age-adjusted D-Dimer, no patients experienced a PE at three-month follow-up (0/70, 0% 95% CI 0.0 – 6.5%) (Bannelier 2024). This data argues for adding a D-Dimer to the evaluation approach in the high pre-test probability group. However, there are a number of important caveats: 1) selection bias – not all high pre-test probability patients had a D-Dimer sent, 2) wide confidence intervals with a worst-case scenario of 6.5% (well above the 2% threshold) and 3) the “high-risk” group wasn’t that high risk for PE (PE rate ~ 30%. Historically PE rate in high-risk ~ 60%). Perhaps most important is the fact that the vast majority of patients (90%) who had a high pre-test probability had a positive D-Dimer. While a negative age-adjusted D-Dimer may safely exclude PE in a high pretest probability patient, it’s far more likely that the D-Dimer will be positive, resulting in a delay of definitive testing.
Bottom Line: It may be reasonable to forgo a CTPA in a high pre-test probability for PE patient if an age-adjusted D-Dimer is negative. However, the low rate of negative D-Dimers in this group makes this a nonviable clinical strategy; it is more likely that obtaining a D-Dimer simply delays care instead of adding value. If the patient errantly had a D-Dimer sent and it was negative, a clinician could consider skipping a CTPA, though additional data should be obtained.
References
Bannelier H et al. Failure rate of D-Dimer testing in patients with high clinical probability of pulmonary embolism: Ancillary analysis of three European studies. Acad Emerg Med 2024. PMID: 39487597
REBEL EM: D-Dimer in High Risk PE: A Gamble Worth Taking?
Age-Adjusted D-Dimer:
- Core EM: Age Adjusted D-Dimer in PE – The ADJUST-PE Trial
- REBEL EM: PEGeD Study – Is It Safe to Adjust the D-Dimer Threshold for Clinical Probability?
- REBEL EM: Age Adjusted D-Dimer Testing
- The Bottom Line: PEG-eD
- St. Emlyn’s: Level Pegging? JC and the PEGeD Study
- JournalFeed: Is it Time to Adjust D-Dimer Thresholds to Our Clinical Pretest Probability?
- The SGEM: SGEM #282 – It’s All ‘Bout That Bayes, ‘Bout That Bayes – No Trouble – In Diagnosing Pulmonary Embolism
YEARS Criteria
- REBEL EM: The YEARS Study – Simplified Diagnostic Approach to PE
- EM Lit of Note: YEARS, But Wells
ACEP Clinical Policy:
- REBEL EM: ACEP Clinical Policy on Acute VTE 201
FOAMCast: Pulmonary Embolism Risk Stratification and ACEP Clinical Policy
