Age-adjusted D-dimer cut-off leads to more efficient diagnosis of venous thromboembolism in the emergency department: a comparison of four assays

Abstract

Essentials Age-adjusted D-dimer cut-offs decrease the false positives in the elderly. Four D-dimer assays were compared in venous thromboembolism outpatients in an emergency ward. Age-adjusted cut-off resulted in improved specificity with maintained sensitivity for all assays. There was a substantial decrease in false positive results, especially in the older population.

Summary: Background The study compares different D-dimer assays and age-adjusted cut-offs in outpatients with suspected venous thromboembolism (VTE). The plasma concentration of this sensitive biomarker is increased by activated coagulation, but also by several conditions that are linked to an increased risk of VTE. One such condition is old age, which poses a common clinical problem where many prefer not to analyze D-dimer in elderly patients. Age-adjusted cut-offs have been validated for both deep venous thrombosis (DVT) and pulmonary embolism, aiming to increase specificity without notably decreasing sensitivity. Objectives We evaluated four common D-dimer assays in parallel, with and without applying age-adjusted cut offs for VTE. Patients/methods The prospective single-center study was conducted in 940 outpatients attending the emergency department with clinically suspected pulmonary embolism or DVT. Four automated D-dimer assays were compared (Siemens INNOVANCE^® , Roche Tina-quant, Medirox MRX and STA^® -Liatest^® D-Di PLUS). Results All assays performed with areas under the ROC curve (AUC) > 0.9 and maintained their sensitivities after implementation of age-adjusted cut-offs. Specificities increased by 6-7% and number needed to test decreased by < 0.3. The rate of false positive results decreased by 6% overall and by 10-20% for patients ≥ 70. Conclusions Age-adjusted cut-offs resulted in maintained high sensitivity and a modest improvement in specificity and number needed to test for all evaluated D-dimer assays. There was a significant reduction in false positive results, which reflects avoidable unnecessary imaging without any compromise of clinical safety. This suggests a potential to benefit the management of VTE in elderly patients, both clinically and economically.

Keywords: age factors; fibrin fibrinogen degradation products; predictive value of tests; sensitivity and specificity; venous thromboembolism.