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Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis.

Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA, van Delden JJ, Moons KG, Reitsma JB - BMJ (2013)

Bottom Line: The specificity of the conventional cut-off value decreased with increasing age, from 57.6% (95% confidence interval 51.4% to 63.6%) in patients aged 51-60 years to 39.4% (33.5% to 45.6%) in those aged 61-70, 24.5% (20.0% to 29.7% in those aged 71-80, and 14.7% (11.3% to 18.6%) in those aged >80.Age adjusted cut-off values revealed higher specificities over all age categories: 62.3% (56.2% to 68.0%), 49.5% (43.2% to 55.8%), 44.2% (38.0% to 50.5%), and 35.2% (29.4% to 41.5%), respectively.Sensitivities of the age adjusted cut-off remained above 97% in all age categories.

View Article: PubMed Central - PubMed

Affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, 3508GA Utrecht, Netherlands.

ABSTRACT

Objective: To review the diagnostic accuracy of D-dimer testing in older patients (>50 years) with suspected venous thromboembolism, using conventional or age adjusted D-dimer cut-off values.

Design: Systematic review and bivariate random effects meta-analysis.

Data sources: We searched Medline and Embase for studies published before 21 June 2012 and we contacted the authors of primary studies.

Study selection: Primary studies that enrolled older patients with suspected venous thromboembolism in whom D-dimer testing, using both conventional (500 µg/L) and age adjusted (age × 10 µg/L) cut-off values, and reference testing were performed. For patients with a non-high clinical probability, 2 × 2 tables were reconstructed and stratified by age category and applied D-dimer cut-off level.

Results: 13 cohorts including 12,497 patients with a non-high clinical probability were included in the meta-analysis. The specificity of the conventional cut-off value decreased with increasing age, from 57.6% (95% confidence interval 51.4% to 63.6%) in patients aged 51-60 years to 39.4% (33.5% to 45.6%) in those aged 61-70, 24.5% (20.0% to 29.7% in those aged 71-80, and 14.7% (11.3% to 18.6%) in those aged >80. Age adjusted cut-off values revealed higher specificities over all age categories: 62.3% (56.2% to 68.0%), 49.5% (43.2% to 55.8%), 44.2% (38.0% to 50.5%), and 35.2% (29.4% to 41.5%), respectively. Sensitivities of the age adjusted cut-off remained above 97% in all age categories.

Conclusions: The application of age adjusted cut-off values for D-dimer tests substantially increases specificity without modifying sensitivity, thereby improving the clinical utility of D-dimer testing in patients aged 50 or more with a non-high clinical probability.

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Fig 2 Number of extra patients per 1000 patients with non-high clinical probability in whom venous thromboembolism would be correctly or falsely excluded by application of age adjusted D-dimer cut-off values instead of conventional cut-off values
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fig2: Fig 2 Number of extra patients per 1000 patients with non-high clinical probability in whom venous thromboembolism would be correctly or falsely excluded by application of age adjusted D-dimer cut-off values instead of conventional cut-off values

Mentions: Based on hypothetical cohorts of 1000 patients for each age category, we calculated the numbers of extra patients in whom imaging examination would, correctly or wrongly, be avoided by using the age adjusted instead of the conventional D-dimer cut-off value (table 4). This would result in a correct exclusion of venous thromboembolism in 40 (95% confidence interval 38 to 41), 85 (81 to 86), 155 (141 to 164), and 175 (153 to 194) extra patients at the expense of 1 (0 to 4) extra missed cases for those aged 51-60 years, 2 (2 to 5) for those aged 61-70 years, 3 (2 to 4), for those aged 71-80 years, and 4 (2 to 6) for those aged more than 80 years. D-dimer testing would rule out venous thromboembolism in 124 per 1000 non-high risk patients aged more than 80 years if the conventional cut-off value would be applied, whereas the application of the age adjusted D-dimer cut-off value results in exclusion of venous thromboembolism in 303 per 1000 of these patients. The positive predictive value was 21.2% (95% confidence interval 19.1% to 23.2%) in patients aged more than 80 years and 29.1% (25.3% to 33.1%) in patients aged 50 years or less. To examine the influence of the prevalence on this figure we also compared these numbers for the lowest and highest prevalence of venous thromboembolism of the non-high risk patients within each age category of the studies in this meta-analysis (fig 2). The relative merit of application of the age adjusted cut-off value instead of the conventional cut-off value was higher in the case of a low prevalence (44-194 correct v 0-2 falsely excluded cases) compared with a high prevalence (31-150 correctly v 2-7 falsely excluded cases) (see fig 2 and supplementary appendix 5).


Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis.

Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA, van Delden JJ, Moons KG, Reitsma JB - BMJ (2013)

Fig 2 Number of extra patients per 1000 patients with non-high clinical probability in whom venous thromboembolism would be correctly or falsely excluded by application of age adjusted D-dimer cut-off values instead of conventional cut-off values
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643284&req=5

fig2: Fig 2 Number of extra patients per 1000 patients with non-high clinical probability in whom venous thromboembolism would be correctly or falsely excluded by application of age adjusted D-dimer cut-off values instead of conventional cut-off values
Mentions: Based on hypothetical cohorts of 1000 patients for each age category, we calculated the numbers of extra patients in whom imaging examination would, correctly or wrongly, be avoided by using the age adjusted instead of the conventional D-dimer cut-off value (table 4). This would result in a correct exclusion of venous thromboembolism in 40 (95% confidence interval 38 to 41), 85 (81 to 86), 155 (141 to 164), and 175 (153 to 194) extra patients at the expense of 1 (0 to 4) extra missed cases for those aged 51-60 years, 2 (2 to 5) for those aged 61-70 years, 3 (2 to 4), for those aged 71-80 years, and 4 (2 to 6) for those aged more than 80 years. D-dimer testing would rule out venous thromboembolism in 124 per 1000 non-high risk patients aged more than 80 years if the conventional cut-off value would be applied, whereas the application of the age adjusted D-dimer cut-off value results in exclusion of venous thromboembolism in 303 per 1000 of these patients. The positive predictive value was 21.2% (95% confidence interval 19.1% to 23.2%) in patients aged more than 80 years and 29.1% (25.3% to 33.1%) in patients aged 50 years or less. To examine the influence of the prevalence on this figure we also compared these numbers for the lowest and highest prevalence of venous thromboembolism of the non-high risk patients within each age category of the studies in this meta-analysis (fig 2). The relative merit of application of the age adjusted cut-off value instead of the conventional cut-off value was higher in the case of a low prevalence (44-194 correct v 0-2 falsely excluded cases) compared with a high prevalence (31-150 correctly v 2-7 falsely excluded cases) (see fig 2 and supplementary appendix 5).

Bottom Line: The specificity of the conventional cut-off value decreased with increasing age, from 57.6% (95% confidence interval 51.4% to 63.6%) in patients aged 51-60 years to 39.4% (33.5% to 45.6%) in those aged 61-70, 24.5% (20.0% to 29.7% in those aged 71-80, and 14.7% (11.3% to 18.6%) in those aged >80.Age adjusted cut-off values revealed higher specificities over all age categories: 62.3% (56.2% to 68.0%), 49.5% (43.2% to 55.8%), 44.2% (38.0% to 50.5%), and 35.2% (29.4% to 41.5%), respectively.Sensitivities of the age adjusted cut-off remained above 97% in all age categories.

View Article: PubMed Central - PubMed

Affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, 3508GA Utrecht, Netherlands.

ABSTRACT

Objective: To review the diagnostic accuracy of D-dimer testing in older patients (>50 years) with suspected venous thromboembolism, using conventional or age adjusted D-dimer cut-off values.

Design: Systematic review and bivariate random effects meta-analysis.

Data sources: We searched Medline and Embase for studies published before 21 June 2012 and we contacted the authors of primary studies.

Study selection: Primary studies that enrolled older patients with suspected venous thromboembolism in whom D-dimer testing, using both conventional (500 µg/L) and age adjusted (age × 10 µg/L) cut-off values, and reference testing were performed. For patients with a non-high clinical probability, 2 × 2 tables were reconstructed and stratified by age category and applied D-dimer cut-off level.

Results: 13 cohorts including 12,497 patients with a non-high clinical probability were included in the meta-analysis. The specificity of the conventional cut-off value decreased with increasing age, from 57.6% (95% confidence interval 51.4% to 63.6%) in patients aged 51-60 years to 39.4% (33.5% to 45.6%) in those aged 61-70, 24.5% (20.0% to 29.7% in those aged 71-80, and 14.7% (11.3% to 18.6%) in those aged >80. Age adjusted cut-off values revealed higher specificities over all age categories: 62.3% (56.2% to 68.0%), 49.5% (43.2% to 55.8%), 44.2% (38.0% to 50.5%), and 35.2% (29.4% to 41.5%), respectively. Sensitivities of the age adjusted cut-off remained above 97% in all age categories.

Conclusions: The application of age adjusted cut-off values for D-dimer tests substantially increases specificity without modifying sensitivity, thereby improving the clinical utility of D-dimer testing in patients aged 50 or more with a non-high clinical probability.

Show MeSH
Related in: MedlinePlus