Acute pulmonary embolism (PE) is a common disease associated with high degrees of morbidity and mortality. The D-dimer assay has the potential to be a valuable test in the workup of PE as it is sensitive for thrombus formation. Unfortunately, specificity is low and indiscriminate use can lead to increased advanced imaging. When combined with a clinical decision model, like Wells, a negative D-dimer value can be used to effectively rule out pulmonary embolism. However, D-dimer is affected by various factors including malignancy, chronic disease, autoimmune disorders and age. Decreased specificity diminishes it’s utility with increased patient age. This study tried to reconcile that change by applying an age adjusted D-dimer value for patients in the workup of PE.
Is there an increased diagnostic yield of elderly patients with suspected PE when using an age-adjusted D-dimer cutoff defined as age x 10 in patients 50 years or older?
3346 consecutive patients with clinically suspected PE defined as (1) acute onset of worsening shortness of breath or (2) chest pain without another obvious etiology presenting to 19 centers across Belgium, France, the Netherlands and Switzerland between January 1, 2010 and February 28, 2013
Patients deemed low-risk based on revised Geneva or 2-level Wells score with a D-dimer value between the conventional cutoff of 500 µg/l and their age-adjusted cutoff did not undergo CTPA and were left untreated and formally followed-up for a 3-month period.
Adjudicated thromboembolic events during the 3 month follow up period among patients not treated with anticoagulants.
Prospective, observational study.
PE suspicion raised > 24 hours after admission to the hospital, already receiving an anticoagulant, allergy to contrast medium, impaired renal function (creatinine clearance less than 30 mL/min as per the Cockcroft-Gault formula), life expectancy of less than 3 months, ongoing pregnancy, or inaccessibility for follow-up.
- Thromboembolic events (w/in 3 months) D-dimer level < 500 µg/L was 1/810 (0.1%)
- Thromboembolic events (w/in 3 months) D-dimer level > 500 µg/L but below age-adjusted cutoff was 1/331 patients (0.3% CI 0.1 – 1.7%)
- In patients > 75 years, age-adjusted D-dimer level vs 500 µg/l conventional cutoff, exclusion increased from 6.4% to 29.7% without additional false negatives
- Prevalence of PE among centers was 19%
- 2898 patients with non-high or unlikely clinical probability.
- 2% with D-dimer level lower than absolute 500 µg/l.
- 6% with D-dimer level between 500 and age-adjusted cutoff.
- 51% with D-dimer level > age-adjusted cutoff.
- 3 month failure rate in patients with a D-dimer level > age-adjusted cutoff was 7/1481 (0.5%)
- Multi-center study
- Excellent methods with parameters very similar to original Wells study
- 6 different D-dimer assays were used with traditional cutoffs varying from 200-500 µg/l
- Autopsies were not performed on all deceased individuals, cannot complete exclude PE as cause of death.
- Prevalence of PE is similar to other European studies but is considerably higher than in North American studies.
“Compared with a fixed D-dimer cutoff of 500 µg/l, the combination of pretest clinical probability assessment with age-adjusted D-dimer cutoff was associated with a larger number of patients in whom PE could be considered ruled out with a low likelihood of subsequent clinical venous thromboembolism”
Using an age-adjusted D-dimer cutoff can increase the number of patients that can be safely ruled out for PE/DVT. Based on the study’s results, conventional D-dimer cutoffs would have 1 in 16 PE ruled out. In an age-adjusted scenario, 1 in 3.4 would have PE ruled out without increases in missed VTE. However differing prevalence levels when compared to North America and different D-dimer assays with different cutoffs limits this study’s applicability across multiple centers.
Potential Impact To Current Practice
Wide use of the adjusted D-dimer cutoffs could potentially decrease the use of advanced imaging to rule out PE.
Consider applying age-adjustment to the D-dimer test in patients over 50 who are low risk for PE to decrease the use of advanced imaging to rule out PE.
Sharp AL et al. An Age-Adjusted D-dimer Threshold for Emergency Department Patients with Suspected Pulmonary Embolus: Accuracy and Clinical Implications. Ann Emerg Med 2015. PMID: 26320520