Raising the D-dimer bar: a narrative review of the age-adjusted D-dimer threshold

D-dimers play a key role in diagnosing venous thromboembolism (VTE) due to high negative predictive value in excluding VTE in patients with a nonhigh clinical probability. However, D-dimer levels naturally increase with age, complicating their interpretation in elderly patients. To address this, an age-adjusted threshold multiplying the patient's age by 10 (μg/L), starting from age 50 years, has been proposed in several studies, to exclude the diagnosis of VTE in patients over 50 years with a nonhigh clinical probability. This narrative review discusses the establishment as well as the efficiency and safety of the age-adjusted threshold multiplying the patient's age by 10 (μg/L), with a focus on the HemosIL D-dimer assays. Overall, the age-adjusted D-dimer threshold has demonstrated enhanced specificity without compromising sensitivity in excluding VTE in patients with suspected pulmonary embolism and nonhigh clinical probability in emergency department settings. By improving specificity, reducing imaging reliance, and lowering costs, the age-adjusted threshold offers a cost-effective and efficient strategy for optimizing VTE management. However, real-world diagnostic strategy studies remain limited, particularly for deep vein thrombosis. Retrospective studies dominate this area, and the cautious stance of scientific societies reflects the absence of large-scale, prospective trials. Emerging evidence suggests the age-adjusted threshold may be as safe and efficient as the conventional approach for deep vein thrombosis exclusion. More than 30 commercial assays are available for D-dimer testing, and the age-adjusted threshold is not validated with all commercially available D-dimer techniques. This underscores the critical need for assay-specific validation before age-adjusted thresholds can be reliably integrated into routine clinical practice.