D-dimer testing and pulmonary embolism

A negative D-dimer is useful in ruling out pulmonary embolism (PE) in patients who do not have a high pre-test probability of of PE.

A Cochrane review included 4 studies with a total of 1 585 adults. The aim of the review was to investigate the ability of the D-dimer test to rule out a diagnosis of acute pulmonary embolism (PE) in patients treated in hospital outpatient and accident and emergency settings who have had a pre-test probability of PE determined according to a clinical prediction rule (CPR). CPRs used were Geneva (including Revised and Revised Simplified), Wells (two-level, three-level and simplified) and the Charlotte rule. Studies used pulmonary angiography, V/Q scintigraphy, selective pulmonary angiography (CTPA) and magnetic resonance pulmonary angiography (MRPA) as reference standard tests. Quantitative D-dimer assays demonstrated high sensitivity in all 4 studies, but with high levels of false-positive results, especially among those over the age of 65 years. Estimates of sensitivity ranged from 80% to 100%, and estimates of specificity from 23% to 63%. Among persons with low or intermediate pre-test probability of PE according to CPR, sensitivity of D-dimer tests ranged from 94% to 100%.

A systematic review included 78 studies, of which 31 directly compared an ELISA with other D-dimer assays. Overall prevalence was 36% for deep venous thrombosis (DVT) and 25% for pulmonary embolism (PE). For the diagnosis of DVT, the sensitivity of the ELISA and quantitative rapid ELISA was higher than of semiquantitative or quantitative latex agglutination assays (95–96% vs. 79–86%). ELISAs had negative likelihood ratios of 0.10–0.25. For the diagnosis of PE, the ELISA and quantitative rapid ELISA were more sensitive than semiquantitative latex (96–97% vs. 80–89%). ELISAs had negative likelihood ratios of 0.7–0.18. The sensitivity of whole blood d-dimer assay was 86% and 83%, respectively. For the diagnosis of DVT, the specificity of ELISAs was 40–44% and of latex assays 61–66%. For the diagnosis of PE, specificities were 41–51% and 47–56%, respectively.Commentary: Negative results on an ELISA or quantitative rapid ELISA reliably exclude a diagnosis of venous thromboembolism, at least in patients with low to moderate pretest probability of disease (<30%). For excluding PE or DVT, a negative result on quantitative rapid ELISA is as diagnostically useful as a normal lung scan or negative duplex ultrasonography finding.