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

Abstract

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.

Can the use of an age-adjusted D-dimer cut-off value help in our diagnosis of suspected pulmonary embolism?

“…Another contemporary study by Farm et al investigated ageadjusted D-dimer for four different D-dimer assays and found the use of age-adjusted D-dimer approach improved specificity with maintained sensitivity in all four assays with a substantial decrease in false positives, similar to our study. 13…”

Study on the Risk Factors of Deep Vein Thrombosis (DVT) in Patients With Lower Extremity Fracture

“…However, the D-dimer level increases with age and elderly patients are more prone to false-positive test results, which reduces the speci city of detection in these patients; therefore, studies have demonstrated the need to set the best cut-off value according to age to increase the speci city of detection [24] . In addition, any increased brin or decomposition process, such as pregnancy, cancer, trauma, in ammation, infection, etc., will increase the D-dimer level; therefore, an increase in the D-dimer level cannot be used for the speci c detection of VTE [25] . The D-dimer level alone is often unreliable for the diagnosis of DVT; however, as a low-cost and readily available biomarker, an elevated D-dimer level is useful for clinicians to identify or exclude VTE in patients based on symptoms and imaging ndings [26] .…”

Diagnostic Accuracy in Acute Venous Thromboembolism: Comparing D-Dimer, Thrombin Generation, Overall Hemostatic Potential, and Fibrin Monomers

“…Samples were taken from the Karolinska Age Adjusted D-Dimer study (DFW-VTE). 5 In short, 954 consecutive outpatients with clinically suspected pulmonary embolism (PE) or deep venous thrombosis (DVT) in the lower limb were prospectively recruited from the emergency department of Karolinska University Hospital in Huddinge, Sweden, between April 2014 and May 2015. Medical students were separately enrolled as healthy controls for post hoc analysis.…”

“…4 The specificity of D-dimer is low at the chosen cutoff, with false positive results in up to 30% of tested patients with suspected VTE. 5 The low specificity is partially due to increased levels in patients with comorbidities. 6 Increasing the effectiveness of the diagnostic process could potentially have major clinical and economical beneficial effects on the management of VTE.…”