IMPORTANCE: The age-adjusted D-dimer cutoff (age × 10 µg/L in patients 50 years or older), safely increases the diagnostic yield of D-dimer in patients with suspected pulmonary embolism but has not been validated in patients with suspected leg deep vein thrombosis (DVT).
OBJECTIVE: To prospectively validate whether using an age-adjusted D-dimer cutoff allows clinicians to safely rule out DVT.
DESIGN, SETTING, AND PATIENTS: Multicenter, multinational prospective management outcome study conducted in 27 centers in Belgium, Canada, France, and Switzerland between January 2015 and October 2022 (last follow-up visit, January 30, 2023) and including outpatients presenting to the emergency department with suspected DVT.
INTERVENTIONS: Patients were assessed by a sequential diagnostic strategy based on the assessment of clinical pretest probability by the Wells score, a highly sensitive D-dimer test, and leg compression ultrasonography. Patients in whom DVT was ruled out were followed up for a 3-month period.
MAIN OUTCOME AND MEASURE: The primary outcome was the rate of adjudicated symptomatic venous thromboembolic events during follow-up in patients in whom DVT was ruled out based on a D-dimer value between the conventional cutoff of 500 µg/L and their age-adjusted cutoff.
RESULTS: A total of 3205 patients were included. Median age was 59 years, and 1737 (54%) were female. DVT prevalence was 14%. Among the 2169 patients with a non-high or unlikely clinical probability, 531 (24.5% [95% CI, 22.7%-26.4%]) had a D-dimer level less than 500 µg/L, and 161 additional patients (7.4% [95% CI, 6.4%-8.6%]) had a D-dimer level between 500 µg/L and their age-adjusted cutoff. No failures were identified in patients with a D-dimer level 500 µg/L or greater but below the age-adjusted cutoff (0% [95% CI, 0%-2.3%]). Among patients 75 years or older, using the age-adjusted cutoff instead of the 500-µg/L cutoff increased the proportion of negative D-dimer from 33 of 379 (8.7% [95% CI, 6.3%-12.0%]) to 99 of 379 (26.1% [95% CI, 22.0%-30.8%]), without any false-negative test results.
CONCLUSIONS AND RELEVANCE: The age-adjusted D-dimer cutoff may safely rule out DVT and was associated with a larger number of patients in whom DVT could be effectively ruled out.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02384135.
| Discipline Area | Score |
|---|---|
| Emergency Medicine |  |
| Hemostasis and Thrombosis | |
| Hospital Doctor/Hospitalists |  |
| Internal Medicine | |
Physiologically, I do not understand how age-adjusted D-dimer would accurately rule-out PE yet prove inaccurate for DVT, so I have been applying the age-adjusted D-dimer for DVT rule-out independent of this evidence. This study validates the practice and is likely additive to most clinicians' evidence-based diagnostics approach.
This study tested whether the age-adjusted D-dimer safely rules out deep-vein thrombosis (DVT). In 27 emergency departments in 4 countries, 3205 adults with suspected DVT were enrolled. Patients with a high or likely clinical probability according to the Well's criteria got compression ultrasonography (CU). In patients with a low/intermediate or unlikely pretest probability, a D-dimer test was performed. D-dimer results were interpreted according to the age-adjusted cutoff: in patients younger than 50 years, DVT was excluded if the D-dimer was <500 µg/L. In those 50 years or older, the D-dimer test was considered negative if the result was < age x 10 in µg/L. All patients received a 3-month telephone follow-up. Of the 161 patients who had an age-adjusted D-dimer cutoff, none developed a DVT (95% confidence interval < 2%). The total number of CUs actually done in the cohort was 2762, so invoking the age-adjusted protocol would reduce CU by 161/(2762+161) = 5.5%.
This prospective study showed that the use of age-adjusted D-Dimer (AADD) could be used to safely rule out acute DVT in the lower extremities compared with using the traditional cutoff of 500 ug/L. The strength of this study is the large, multi-site, multi-national design. This should not be a surprise since multiple studies show the safety and utility of AADD. What would be interesting to see is other DDimer cutoffs can be used as has been explored with PE (eg low-pretest probability and D-Dimer <1000). Regardless, clinicians should be comfortable using AADD for ruling out both PE and DVT.
It is useful to know that an age-adjusted cutoff can be used to rule out lower extremity deep venous thrombosis and reduce unnecessary testing for patients and minimize costs.
Probably most relevant to ER physicians, but still good to know.
