Diagnostic accuracy of D‐dimer test for exclusion of venous thromboembolism: a systematic review

Abstract

Summary. Background: The reported diagnostic accuracy of the D-dimer test for exclusion of deep vein thrombosis (DVT) and pulmonary embolism (PE) varies. It is unknown to what extent this is due to differences in study design or patient groups, or to genuine differences between D-dimer assays. Methods: Studies evaluating the diagnostic accuracy of the D-dimer test in the diagnosis of venous thromboembolism were systematically searched for in the MEDLINE and EMBASE databases up to March 2005. Reference lists of all included studies and of reviews related to the topic of the present meta-analysis were manually searched for other additional potentially eligible studies. Two reviewers independently extracted study characteristics using standardized forms. Results: In total, 217 Ddimer test evaluations for DVT and 111 for PE were analyzed. Several study design characteristics were associated with systematic differences in diagnostic accuracy. After adjustment for these features, the sensitivities of the D-dimer enzyme-linked immunofluorescence assay (ELFA) (DVT 96%; PE 97%), microplate enzyme-linked immunosorbent assay (ELISA) (DVT 94%; PE 95%), and latex quantitative assay (DVT 93%; PE 95%) were superior to those of the whole-blood Ddimer assay (DVT 83%; PE 87%), latex semiquantitative assay (DVT 85%; PE 88%) and latex qualitative assay (DVT 69%; PE 75%). The latex qualitative and whole-blood D-dimer assays had the highest specificities (DVT 99%, 71%; PE 99%, 69%). Conclusions: Compared to other D-dimer assays, the ELFA, microplate ELISA and latex quantitative assays have higher sensitivity but lower specificity, resulting in a more confident exclusion of the disease at the expense of more additional imaging testing. These conclusions are based on the most up-to-date and extensive systematic review of the topic area, including 184 articles, with 328 D-dimer test evaluations.

D-Dimer Assays in Diagnosis and Management of Thrombotic and Bleeding Disorders

“…[1][2][3][7][8][9][10] However, because D-dimer levels may also be increased in a variety of nonthrombotic disorders, D-dimer is a sensitive but nonspecific marker for venous thrombosis. Consequently, although a positive result is not useful in confirming the diagnosis of DVT or PE, a negative result can aid in the exclusion of these conditions and limit the need for further investigation with expensive and invasive radiologic tests.…”

“…Consequently, although a positive result is not useful in confirming the diagnosis of DVT or PE, a negative result can aid in the exclusion of these conditions and limit the need for further investigation with expensive and invasive radiologic tests. 1,3,[7][8][9][10] In hospitalized and other acutely ill patients commonly affected by the conditions listed in ►Table 1, D-dimer testing has less utility because of the high frequency of false-positive results. 7,11,12 Most of the data validating the use of D-dimer testing in suspected VTE come from evaluations of patients in the ambulatory setting (i.e., outpatient or emergency departments).…”

“…1,3,[7][8][9][10] In hospitalized and other acutely ill patients commonly affected by the conditions listed in ►Table 1, D-dimer testing has less utility because of the high frequency of false-positive results. 7,11,12 Most of the data validating the use of D-dimer testing in suspected VTE come from evaluations of patients in the ambulatory setting (i.e., outpatient or emergency departments). 13 When VTE is suspected but access to diagnostic testing is likely to be delayed, it is common practice to administer empiric heparin or low molecular weight heparin before the diagnosis is confirmed or excluded.…”

“…In a meta-analysis of over 300 studies, ELISAs, enzyme-linked fluorescent assays (ELFAs), and quantitative latex or immunoturbidometric assays were more sensitive for VTE (sensitivity > 90%) than were other assay types (►Table 3). 7 Based on these data, ELISAs and ELFAs, along with the latex immunoturbidometric assays, are generally termed "highly sensitive," while the whole-blood D-dimer assay is considered "moderately sensitive." The more sensitive assays displayed lower specificities for VTE than the less sensitive tests.…”

Diagnosis and management of pulmonary embolism in the elderly

“…In patients with "non-high" clinical probability (low and intermediate groups in a three category score or unlikely group in a dichotomic score), a highly sensitive negative D-dimer safely excludes PE without additional investigations [26]. Sensitive D-dimer tests include those performed by the ELISA technique (median sensitivity 99%; Vidas®, Stratus®, AxSYM®) and by quantitative latex methods (median sensitivity 96%; STA Liatest®, Tinaquant®) [29]. Lower sensitivity D-dimer tests by whole blood agglutination methods (Simpli-RED®) are semi-quantitative, and with a median sensitivity of 87% they can safely exclude PE only in patients with low clinical probability (low group of a three category score or unlikely group in a dichotomic score) [26].…”