Table 10D-dimer – Quality assessment

OutcomeNumber of studiesDesignLimitationsInconsistencyIndirectnessImprecision
Meta-analysis: Pooled sensitivity and specificity85
All D-dimer tests8597Meta- analysis of diagnostic cohortsNo serious limitations (a)Serious inconsistency (b)Serious indirectness (c)No serious imprecision
ELISAs85 (h)58Sub-group data from meta- analysisNo serious limitations(a)Serious inconsistency(b)Serious indirectness(c)No serious imprecision
Latex assays8552Sub-group data from meta- analysisNo serious limitations(a)Serious inconsistency(b)Serious indirectness(c)No serious imprecision
Whole-blood agglutination8529Sub-group data from meta- analysisNo serious limitations(a)Serious inconsistency(b)Serious indirectness(c)No serious imprecision
Non pooled studies
Sensitivity & Specificity 5,50,52,54,106,172,235, 2378DiagnosticSerious limitations (d)Serious inconsistency (e)Serious indirectness (f)Serious imprecision (g)
PPV or NPV5,50,52,54,106,172,235,2378DiagnosticSerious limitations (d)Serious inconsistency (e)Serious indirectness (f)Serious imprecision (g)
3 month VTE rate0Diagnostic or RCT
Mortality0Diagnostic or RCT
a

Reference standards used differ between cohorts, and were dependent on D-dimer or unclear in 14 cohorts (for details see evidence tables in appendix E.2). The threshold value for D-dimer was defined before analysis in 82 cohorts, was defined after analysis in ten and was not clear in seven. D-dimer was measured blind to the reference standard in 43 cohorts and measurement was unclear in 56. The reference standard was interpreted blind to the D-dimer result in 50 cohorts and interpretation was unclear in 49. These potential limitations were considered not severe enough to further reduce our confidence in the estimate of effect.

b

Meta-regression was conducted to investigate heterogeneity. Higher quality studies (prospective studies, those recruiting consecutive patients, those using venography as a reference standard, D-dimer and reference standard measured blind) tended to have higher specificity. Studies that determined the D-dimer threshold after data analysis had higher sensitivity. However, stratification by each significant predictor identified in the meta-regression did not explain the heterogeneity.

c

The main meta-analysis included studies which are almost 20 years old, and all the various types of test (which may have different range of accuracies) are pooled together. The performance of different subgroups of tests was considered. It is likely that a newer test will have better diagnostic accuracy than an older test. The sensitivity and specificity of tests are also dependent on the characteristics of the population these tests are applied on. The studies included had a median prevalence of 36% (range 2 to 78 %)

d

Various limitations in studies, such as unclear whether the same type of ultrasound scan was done for all patients, unclear whether investigators were blinded to the reference/index test and poor reporting of some studies.

e

The range of sensitivity and specificity obtained from various studies were substantial.

f

Unclear whether study patients are representative to the population recommended.

g

Wide range of values obtained

h

ELISA is an acronym for a type of D-dimer test called an “enzyme-linked immunosorbent assay”

From: 5, Diagnosis of deep vein thrombosis

Cover of Venous Thromboembolic Diseases
Venous Thromboembolic Diseases: The Management of Venous Thromboembolic Diseases and the Role of Thrombophilia Testing [Internet].
NICE Clinical Guidelines, No. 144.
National Clinical Guideline Centre (UK).
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