Discordant D-dimer results of two rapid quantitative automated assays are related to age

Abstract

We read with interest the recently published paper by Carrier et al.[1] on the use of D-dimer (DD) in the elderly. This study demonstrates that the combination of a low Wells pre-test probability with a negative DD value safely excludes deep vein thrombosis (DVT) in elderly patients (aged over 60 years). However, the results of this study, based on pooled results of three technically different DD assays, are not totally in agreement with three other studies [2][3][4], and the authors suggest that this discrepancy might be explained by differences in the specificity of the DD assays. DD assays have been extensively evaluated, and meta-analyses were recently performed to determine the best tests [5,6]. One limitation of these approaches is that the findings are mainly based on an indirect comparison of the test performance from various studies and hence, mostly from heterogeneous patient populations.In the study, we compared performances in two rapid quantitative automated DD assays on the same population and demonstrated that age was the main clinical characteristic related to discordant results between the two tests.We previously published a management study of 1134 consecutive non-selected patients clinically suspected of pulmonary embolism (PE) [7]. In this study, DD (cut-off 0.5 mg L )1 , quantitative ELISA test, Vidas Ò D-Dimer; BioMe´rieux, Lyon, France): (V) was determined straight away for 656 patients who fulfilled the criteria of our decision-making. For 608 of these patients, citrated plasma was immediately stored at )80°C, and a second DD measurement performed retrospectively using a rapid immunoturbidimetric assay (cut-. Data were complete for 603 patients (five patients were lost at follow-up) who achieved a 3-month follow-up. DD were found negative (<0.5 mg L )1) by both methods (L)/V)) in 259 patients (43%; mean age 50.4 years, SD 16.6). The mean DD values for the two tests were not statistically different. False negatives accounted for 1.92% (CI 95% 0.26-3.58%) and this was identical for the two methods. DD were found to be positive ( ‡0.5 mg L )1) by both methods (L+/V+) in 277 patients (mean age 64.2 years, SD 14). Results were not concordant for 67 (11%) patients, of these, 63 (94%) patients neither had PE nor develop PE during the 3-month follow-up. Among these 67 discordant results, 54 were L)/V+ and 13 L+/V). Three patients (4.5%, 95% CI 0-9%) had PE in the L)/V+ group, comparable with one (1.5%, 95% CI 0-4.3%) (P = 0.6) in the L+/V) group. In fact, all these patients were at high clinical probability. Conversely, 51 of the 67 with discordant results (76.1%, 95% CI 65.9-86.3) were L)/ V+ and did not have any thromboembolic events, compared with 12 (17.9%, 95% CI 8-27.1%) in the L+/V) group (P < 0.0001). To explain this discrepancy in the positive rate between the two tests, we analysed the performances in each test related to the patientsÕ clinical characteristics. Both gender and ward origin of the 67 patients with discrepant results did not differ significantly from those of the 536 patie...

Comparison of five D-dimer reagents and application of an age-adjusted cut-off for the diagnosis of venous thromboembolism in emergency department

“…AX, Axsym D-dimer; CI, confidence interval; HS, HemosIL DDi HS; IN, Innovance DDimer; LI, STA Liatest Ddi; NNT, number needed to test to find one normal Ddimer test result; NPV, negative predictive value; VI, VIDAS D-dimer. This confirms that discordant D-dimer results of different quantitative assays are often related to age [15][16][17]. This is due to differences in mean D-dimer values in the low D-dimer range (<1000 ng/ml).…”

“…However, 20 years after its first use in the diagnostic workup of suspected VTE, there is still a lack of standardization of D-dimer assay values between different assays due to the complexity of the D-dimer entity [1]. These discrepancies between different D-dimer assays as well as the two different reporting units in use and the influences of other variables such as age of the patient have led to a considerable uncertainty concerning the cut-off values used in exclusion of VTE [1,[15][16][17][18][19][20]. These discrepancies between different D-dimer assays as well as the two different reporting units in use and the influences of other variables such as age of the patient have led to a considerable uncertainty concerning the cut-off values used in exclusion of VTE [1,[15][16][17][18][19][20].…”

Questioning the use of an age‐adjusted D‐dimer threshold to exclude venous thromboembolism: analysis of individual patient data from two diagnostic studies: comment

“…This could also interfere with conventional or age‐adjusted test performances. Indeed, we previously published an analysis on discordant D‐dimer results of these two rapid quantitative tests . Although the two DD assays were shown to have a high negative predictive value, these two assays statistically differed with regard to positive results, with a higher rate above the cut‐off with the VIDAS assay.…”