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

TL;DR

This paper reviews how adjusting D-dimer thresholds based on age improves diagnosing blood clots in older patients without reducing accuracy.

Contribution

The paper highlights the benefits and limitations of using an age-adjusted D-dimer threshold (age × 10 μg/L) for diagnosing venous thromboembolism in older patients.

Findings

Age-adjusted D-dimer thresholds improve specificity without reducing sensitivity in excluding VTE in older patients.

The threshold reduces imaging use and costs but lacks validation across all commercial D-dimer assays.

More prospective studies are needed to confirm safety and efficiency for deep vein thrombosis.

Abstract

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.

•D-dimer levels naturally increase with age.•D-dimers exclude venous thromboembolism with a high negative predictive value.•An age-adjusted threshold (age × 10 μg/L) has been proposed for patients over 50 years old.•This threshold is not validated across all commercially available D-dimer assay.

D-dimer levels naturally increase with age.

D-dimers exclude venous thromboembolism with a high negative predictive value.

An age-adjusted threshold (age × 10 μg/L) has been proposed for patients over 50 years old.

This threshold is not validated across all commercially available D-dimer assay.

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