Age‐adjusted D‐dimer cut‐off levels to rule out venous thromboembolism in patients with non‐high pre‐test probability: Clinical performance and cost‐effectiveness analysis

Abstract

As aging was found to be associated with increased D-dimer levels, the question arose whether D-dimer measurement was useful in the diagnostic strategy of venous thromboembolism (VTE) in elderly patients. To compare retrospectively the performance of six diagnostic strategies based on the three-level Wells scores and various cut-off levels for D-dimer, evaluated using the HemosIL D-Dimer HS 500 assay, in a derivation cohort of 644 outpatients with non-high pretest probability (PTP) of VTE. The clinical usefulness of the best-performing strategy was then confirmed in a multicenter validation study involving 1255 consecutive outpatients with non-high PTP. The diagnostic strategy based on the age-adjusted cut-off level calculated by multiplying the patient's age by 10 above 50years was found to perform the best in the derivation study with a better sensitivity-to-specificity ratio than the conventional strategy based on the fixed cut-off level (500ng/ml), a higher specificity and a negative predictive value (NPV) above 99%. Such an increase in test specificity was confirmed in the validation cohort, with the NPV remaining above 99%. Taking into account the local reimbursement rates of diagnostic tests, using this strategy led to a 6.9% reduction of diagnostic costs for pulmonary embolism and a 5.1% reduction for deep vein thrombosis, as imaging tests would be avoided in a higher percentage of patients. The diagnostic strategy of VTE based on the age-adjusted cut-off level for D-dimer in patients over 50years was found to be safe, with NPV above 99%, and cost-effective.