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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 sourcesWe 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. ConclusionsThe 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. IntroductionD-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⇓).1-3 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).4 5 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%.4-8 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 diagnosticCorrespondence to: H J Schouten h.j.schouten-3@umcutrecht.nl Extra material supplied by the author (see

BACKGROUND: Prediction models combine patient characteristics and test results to predict the presence of a disease or the occurrence of an event in the future. In the event that test results (predictor) are unavailable, a strategy is needed to help users applying a prediction model to deal with such missing values. We evaluated 6 strategies to deal with missing values.