Use an age-adjusted D-dimer cutoff (patient’s age in years × 10 mcg/L) for patients over age 50 years when evaluating for venous thromboembolism (VTE); it reduces false positives without substantially increasing false negatives.1
Strength of recommendation
A: Based on consistent and good quality patient-centered evidence from a meta-analysis of cohort studies.
Schouten HJ, Geersing GJ, Koek HL, et al. Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and metaanalysis. BMJ. 2013;346:f2492.
A 78-year-old woman with no significant past medical history or recent immobility comes into your clinic complaining of left lower extremity pain and swelling. Her D-dimer is 650 mcg/L. What is your next step?
Although D-dimer is recognized as a reasonable screening tool for VTE, the specificity of D-dimer testing using a conventional cutoff value of 500 mcg/L is particularly poor in patients over 50 years. In low-risk patients over 80 years old, the specificity is 14.7% (95% confidence interval, 11.3%-18.6%).2-5 As a result, conventional D-dimer testing is not very helpful for ruling out VTE in older patients.2-5
Improved testing is needed for a population at heightened risk
In the United States, there are more than 600,000 cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) each year.2 The incidence of PE increases from 1:1000 in younger patients to 8:1000 in older patients4 and the mortality rate can reach 30%.6 The gold standards of venography and pulmonary angiography have been replaced by less burdensome tests, primarily lower extremity duplex ultrasound and computed tomography pulmonary angiogram. However, even these tests are expensive and often present logistical challenges in elderly patients. For these reasons, it is helpful to have a simple, less-expensive tool to rule out VTE in older patients who have signs or symptoms.
STUDY SUMMARY: Using age-adjusted D-dimer cutoffs significantly reduced false positives
Schouten et al1 performed a systematic review and meta-analysis of studies of older patients with suspected VTE who had D-dimer testing using both conventional and age-adjusted cutoff values. The authors searched Medline and Embase for studies published before June 21, 2012 that were performed in outpatient, inpatient, or emergency department settings. They excluded studies of high-risk patients, specifically perioperative patients and those who’d had VTE, cancer, or a coagulation disorder.
Five high-quality studies of 13 cohorts were included in this analysis (N=12,497; 6969 patients >50 years). Each of these studies was a retrospective analysis of patients with a low clinical probability of VTE, as determined by Geneva or Wells scoring. The authors calculated the VTE prevalence and D-dimer sensitivity and specificity for patients ages ≤50, 51 to 60, 61 to 70, 71 to 80, and >80 years.
The specificity of using the conventional D-dimer cutoff value for VTE (500 mcg/L) decreased with age from 57.6% in those ages 51 to 60 to 14.7% in those older than 80. When age-adjusted cutoffs were used (age in years × 10 mcg/L), specificities improved in all age categories, particularly for older patients. For example, using age-adjusted cutoff values improved specificity to 62.3% in patients ages 51 to 60 and to 35.2% in those older than 80 (TABLE). Using a hypothetical model, Schouten et al1 calculated that applying age-adjusted cutoff values would exclude VTE in 303/1000 patients >80 years, compared with 124/1000 when using the conventional cutoff.
The benefit of using an age-adjusted cutoff is the ability to exclude VTE in more patients (1 out of 3 in those older than age 80) while not significantly increasing the number of missed VTE. In fact, the number of missed cases in the older population using the age-adjusted cutoff (approximately 1 to 4 per 1000 patients) is comparable to the false negative rate in those age, ≤50 (3 per 1000). The advantages of an age-adjusted cutoff are most notable with the use of enzyme linked fluorescent assays because these assays have a higher sensitivity and a trend toward lower specificity compared with other assays.