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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 1 Diagnostic investigations in patients with suspected venous thrombembolism. Adapted from Wells 2007,9 Le Gal et al 2006,40 and Wells et al 200157
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fig1: Fig 1 Diagnostic investigations in patients with suspected venous thrombembolism. Adapted from Wells 2007,9 Le Gal et al 2006,40 and Wells et al 200157

Mentions: D-dimer concentrations are highly sensitive for thrombus formation. Hence D-dimer tests are often used to rule-out venous thromboembolism (pulmonary embolism or deep vein thrombosis) in suspected patients with a non-high clinical probability. Patients with a high clinical probability do not require a D-dimer test. In these patients imaging examination is warranted to confirm or refute the diagnosis, irrespective of the D-dimer results (fig 1).123 However, D-dimer concentrations increase with age, which leads to a high proportion of older patients with D-dimer concentrations higher than conventional cut-off values (500 µg/L).45 This in turn leads to a low specificity (that is, more false positive results) of D-dimer testing in older patients suspected of having venous thromboembolism; the specificity is 49% to 67% for patients aged less than 50 years but in older old patients (≥80 years) between 0% and 18%.45678 As imaging is indicated in patients suspected of having venous thromboembolism with a D-dimer concentration above the cut-off value,9 a high proportion of older patients with a non-high clinical probability undergo unnecessary diagnostic investigations. This can be burdensome, especially in older patients, and the yield of this imaging is relatively low (typically 20% or less of patients with clinically suspected venous thromboembolism are actually affected).1011 As a result of a low specificity of D-dimer testing in older patients, some authors dissuade doctors from D-dimer testing in very old patients.4812 Yet this would actually imply referring all suspected older patients for imaging, which is even less desirable.


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 1 Diagnostic investigations in patients with suspected venous thrombembolism. Adapted from Wells 2007,9 Le Gal et al 2006,40 and Wells et al 200157
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Fig 1 Diagnostic investigations in patients with suspected venous thrombembolism. Adapted from Wells 2007,9 Le Gal et al 2006,40 and Wells et al 200157
Mentions: D-dimer concentrations are highly sensitive for thrombus formation. Hence D-dimer tests are often used to rule-out venous thromboembolism (pulmonary embolism or deep vein thrombosis) in suspected patients with a non-high clinical probability. Patients with a high clinical probability do not require a D-dimer test. In these patients imaging examination is warranted to confirm or refute the diagnosis, irrespective of the D-dimer results (fig 1).123 However, D-dimer concentrations increase with age, which leads to a high proportion of older patients with D-dimer concentrations higher than conventional cut-off values (500 µg/L).45 This in turn leads to a low specificity (that is, more false positive results) of D-dimer testing in older patients suspected of having venous thromboembolism; the specificity is 49% to 67% for patients aged less than 50 years but in older old patients (≥80 years) between 0% and 18%.45678 As imaging is indicated in patients suspected of having venous thromboembolism with a D-dimer concentration above the cut-off value,9 a high proportion of older patients with a non-high clinical probability undergo unnecessary diagnostic investigations. This can be burdensome, especially in older patients, and the yield of this imaging is relatively low (typically 20% or less of patients with clinically suspected venous thromboembolism are actually affected).1011 As a result of a low specificity of D-dimer testing in older patients, some authors dissuade doctors from D-dimer testing in very old patients.4812 Yet this would actually imply referring all suspected older patients for imaging, which is even less desirable.

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