van Es N, van der Hulle T, Büller HR, et al. Is stand-alone D-dimer testing safe to rule out acute pulmonary embolism? J Thromb Haemost. 2017 Feb;15(2):323–328.
Systematic review and meta-analysis with post-hoc analysis of data from 6 studies.
Included: Prospective observational studies of hemodynamically stable adults with suspected acute PE evaluated in hospital. The studies had to report the Wells score by Wells ≤ 4 and Wells > 4. Patients with a non-high Wells score and normal D-dimer were followed for 3 months.
Excluded: Not described explicitly.
Retrospective application of D-dimer cut-point 750 µg/L.
Primary: Sensitivity, specificity and negative predictive value of D-dimer cut-point of 750 µg/L.
Secondary: Sensitivity, speciﬁcity and negative predictive value in patients with a low, moderate, and high clinical pretest probability according to the Wells score; patients with active cancer; previous venous thromboembolism (VTE); inpatients.
N = 7,268 patients.
|PE Incidence||7,268||23% (17 to 30)||Low risk of bias||High|
|NPV||97.2% (94.9 to 98.4)|
|LR–||0.099 (0.07 to 0.13)|
|Sensitivity||94.5% (91.5 to 96.4)|
|Specificity||55.8% (47.6 to 63.7)|
|PE Incidence||2,852||10.1% (7.3 to 13.7)||Low risk of bias||High|
|NPV||99.2% (98.6 to 99.5)|
|Sensitivity||94.5% (90.7 to 96.8)|
|Specificity||65.3% (56.9 to 72.9)|
|PE Incidence||4,061||28.8% (22.2 to 36.3)||Low risk of bias||High|
|NPV||95.5% (92.0 to 97.5)|
|Sensitivity||94.2% (90.2 to 96.7)|
|Specificity||48.8% (38.4 to 59.2)|
|PE Incidence||293||58.7% (52.8 to 64.2)||Low risk of bias||High|
|NPV||79.3% (53.0 to 92.8)|
|Sensitivity||96.3% (89.8 to 98.7)|
|Specificity||20.9% (11.3 to 35.3)|
CI = Confidence Interval; LR– = Negative Likelihood Ratio; NPV= Negative Predictive Value; N = number of patients; QUADAS: quality assessment of diagnostic accuracy studies. 62 patients missing in study.
Risk of Bias Assessment
|1||The research question is sensible and answerable.||Maybe||Maybe||Maybe|
|2||The search for studies included all languages, databases, abstracts, bibliographies, and expert contact.||No||No||No|
|3||The search for studies was unbiased and reproducible.||Yes||Yes||Yes|
|4||The selection of studies was unbiased and reproducible.||Yes||Yes||Yes|
|5||The data abstraction was unbiased (e.g., conducted independently by 2 researchers).||Yes||Yes||Yes|
|6||The assessment of the quality of the primary studies was unbiased and reproducible.||Yes||Yes||Yes|
|7||The quality of the primary studies is high.||Yes||Yes||Yes|
|8||The methods used to combine the included primary studies are reported and valid.||Yes||Yes||Yes|
|9||The outcomes are clinically relevant.||Yes||Maybe||Yes|
|10||The statistical heterogeneity of the primary outcome is low (< 25%).||No||No||No|
Funding & Conflicts of Interest
Conflicts of Interest
Potential Threats to Validity
The authors combined results of a limited number of studies from different settings.
Many patients with a D-dimer < 750 µg/L underwent imaging, which identified clots of minimal clinical significance. The selected studies used different D-dimer assays, and in 1 study, different cut-points.
This was a post-hoc analysis with high heterogeneity in the incidence of PE
Kanters D; Worster A; De Wit K & Sharif S.
Competing Interest Disclosure
Dr. de Wit - No conflicts of interest (ICMJE)
Dr. Sharif - No conflicts of interest (ICMJE)