Clinical usefulness and safety of an age-adjusted D-dimer cutoff levels to exclude pulmonary embolism: a retrospective analysis

Abstract

Age-adjusted D-dimer (AADD) appears to increase the proportion of patients in whom pulmonary embolism (PE) can safely be excluded compared with conventional D-dimer (CDD), according to a limited number of studies. The aim if this study was to assess whether the use of an AADD might safely increase the clinical usefulness of CDD for the diagnosis of PE in our setting. Three hundred and sixty two consecutive outpatients with clinically suspected PE in whom plasma samples were obtained to measure D-dimer were included in this post hoc analysis of a previous study. CDD cutoff value was 500 ng/mL and AADD was calculated as (patient's age × 10) ng/mL in patients aged >50. Sensitivity, specificity, clinical usefulness (i.e., proportion of true-negative tests among all patients with suspected PE), and the proportion of false negatives were calculated for both AADD and CDD among patients with low-to-moderate clinical probability of PE according to Well's criteria. PE was confirmed in 98 patients (27%). Among 331 patients with low-to-moderate clinical probability of PE, sensitivity and clinical usefulness were 100 and 27.8% for CDD, respectively, and 100 and 36.5% for AADD, respectively. In 29 patients aged >50 with CDD >500 ng/mL, AADD showed values under its normal cutoff point, without false negatives for the diagnosis of PE (0%, 95% CI 0-11%). AADD increases clinical usefulness notably with respect to that of CDD in patients with clinical suspected PE without losing sensitivity in our cohort. The use of AADD apparently does not reduce the safety of CDD for the exclusion of PE.

Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Suspected Acute Venous Thromboembolic Disease

“…All but one included study used one or more highsensitivity D-dimer assays (eg, VIDAS, Tinaquant, STA-Liatest, Innovance, and D-dimer HS), which generally use a conventional cutoff of FEU at 500 mg/L. [43][44][45][46][47][48][49][50][51] One study used the HemosIL D-dimer assay, which reported results in DDU that are equivalent to approximately half of an FEU, and the formula for age adjustment was adjusted accordingly (ageÂ5 mg/L). 52 The primary concern when using an age-adjusted D-dimer cutoff is whether increasing the threshold increases the risk of missed PEs.…”

“…Safety of the Age-Adjusted D-dimer Strategy ( Table 2) Overall, the 3 Class II studies [43][44][45] found that the miss rate of the age-adjusted D-dimer was similar to a conventional D-dimer cutoff, and that the sensitivities were similar. The prospective study by Righini et al 43 took place at multiple centers in Europe and included 3,324 ED patients with a 19% overall prevalence of PE; 87% were at nonhigh risk, and if the D-dimer result was negative, these patients were discharged without additional testing and without anticoagulation.…”

“…Flores et al 45 conducted a study of 362 ED patients in Spain; all patients had imaging, with the D-dimer level tested for research purposes, and the prevalence of PE in this population was 27%. Among the 331 non-high-risk patients by Wells criteria, there were 0 missed PEs with either the conventional D-dimer or the ageadjusted D-dimer, thus yielding a 100% sensitivity for both the conventional D-dimer and age-adjusted D-dimer cutoffs.…”

Diagnostic utility of an age‐specific cut‐off for d‐dimer for pulmonary embolism assessment when used with various pulmonary embolism risk scores

“…There is a growing body of evidence that age-adjusted ddimer cut-offs have acceptable sensitivity for PE and that their use could avoid a significant proportion of CTPA which carry the risk of adverse effects for patients (such as contrast reaction and contrast nephropathy), often cause inconvenience to patients in terms of an extended ED stay and contribute to reduced ED patient flow by requiring an extended ED stay. 2,5,[7][8][9][10][13][14][15][16] Age-adjusted d-dimer cut-offs are intended to be used in conjunction with a clinical risk score to identify a group of patients in whom PE is unlikely and therefore further imaging can be avoided. There are sparse data comparing the performance of age-adjusted d-dimer cut-offs with the various risk scores in common use.…”

“…6 There is good evidence that 'normal' d-dimer concentrations physiologically increase with age leading to a lower specificity for PE and more false positives in older patients. 4,[7][8][9][10] In fact, d-dimer testing is able to rule out PE in 60% of patients aged <40 years but only 5% for patients aged >80 years. 9,10 This results in an increased number of potentially unnecessary and expensive advanced imaging tests in older patients who are also at increased risk of adverse clinical outcomes, such as contrast-induced nephropathy.…”